Effects of Thermal and Mechanical Challenges

burs).19 Collectively, these results indicate that pulpal 8 HS air reactions to various restorative procedures17-19 are not necessarily caused by excessive heat production. However, it is difficult to precisely position tempera­ ture sensors to detect heat generated during cut­ ting. In addition, the poor thermal conductivity of dentin can result in thermal burns to surface dentin without much change in pulpal temperature.20 HS air-water Pulpal reactions to restorative procedures may / - - - ...... in part be caused indirectly. It is possible that a high LS air-water surface temperature can thermally expand the den­ tinal fluid in the tubules immediately beneath poorly -5 0 5 10 15 20 25 30 35 irrigated burs. If the rate of expansion of dentinal Time(s) fluid is high, the fluid flow across odontoblast pro­ cesses, especially where the odontoblast cell body fills the tubules in predentin, may create shear forces Fig 15-2 Changes in pulpal temperature during low-speed (LS) and high­ sufficiently large to tear the cell membrane21 and speed (HS) cavity preparation with and without air-water cooling. (Modified from Zach and Cohen10 with permission.) induce calcium entry into the ce//,22 possibly leading to cell death.23 This hypothesis suggests that ther­ mally induced fluid shifts across tubules serve as the transduction mechanism for pulp cell injury without causing much change in pulpal temperature. An additional factor that can cause pulpal irrita­ that produced in pulp tissues. However, the out­ tion is evaporative fluid flow.24 Blowing air on dentin come may be influenced by the fact that the blood causes rapid outward fluid flow that can induce the flow per milligram of tissue is higher in the periodon­ same cell injury as the inward fluid flow caused by tal ligament (PDL) than in the pulp.9 heat. For this reason, dry cutting with air is not rec­ In their classic study of pulpal reactions to cavity ommended. Although air blasts lower pulpal tem­ preparation, Zach and Cohen10 demonstrated that perature, 10-13 they induce very rapid outward fluid pulpal temperature was actually lowered during flow in dentinal tubules24-26 that can create shear cavity preparation with high-speed handpieces and stress across odontoblasts and subodontoblastic air-water spray because the water spray was cooler cells and may tear their membranes. than the temperature of the pulp (Fig 15-2) and Recent studies have not been able to confirm because of the high heat capacity of water. They the earlier reports of pulpal damage from thermal recommended what they called the washed-field stress. Because many dental procedures can elevate technique of tooth reduction, in which the tooth sur­ pulpal temperatures by 9°C to 15°C, Baldissara et face is exposed to the air-water spray for 5 seconds al27 evaluated the pulpal response to these tempera­ before cutting. After initial cutting, the bur is lifted ture changes in normal young premolars scheduled off the surface for 1 second following every 4 sec­ for extraction for orthodontic purposes. They placed onds of cutting. When this technique was used, the custom-fabricated metal plates on the teeth. Ther­ pulpal temperature never rose above basal tempera­ moresistors were attached to the plates to produce tures (see Fig 15-2). controlled heat flows. The surface temperature of Cutting at high speeds with air alone used as a the test teeth was measured before and during coolant lowered pulpal temperature prior to cavity controlled heating in nonanesthetized patients who preparation; however, the pulpal temperature rap­ were able to record both prepain and pain sensa­ idly rose as much as 8°C higher than normal during tions during these procedures. the procedure.10 This observation has been con­ The rate of heat application in this study27 was firmed by others.8·9·11-14 The frictional heat produc­ much lower than that used by Zach and Cohen7 and tion will depend on rotational speed15 and torque,14 was selected based on the rate of heating reported the amount of force applied to the bur,1&-1s the cool­ in the literature from a variety of restorative proce­ ing efficiency of the irrigant, and the prior wear and dures (Fig 15-3). In monkeys, Zach and Cohen7 found design of the bur (eg, cutting blades such as carbide that a pulpal temperature of 40.5°C produced pulpal fissure burs or grinding surfaces such as diamond necrosis in 60% of the tested teeth. In the human

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study conducted by Baldissara et al,27 heating of --- Zach and Cohen' (adapted) 52 teeth to 39.5°C to 50.4°C (average 44.5°C) caused ---- Direct provisional crowns (Tjan et al28) pain. This was perceived first as a "swelling" of the 50 Baldissara et al27 tooth, but as the thermal stimulus continued, the 48 - Tooth preparation (air cooled) (Zach and Cohen 10) pain became more intense in magnitude, dull in per­ 46 ceptual character, and poorly localized. These symp­ � 44 toms are hallmarks of unmyelinated C-fiber nocicep­ � � /� � 42 tor pain (see chapters 7 and 8). The occurrence of ., c. postoperative symptoms was followed for 63 to 91 E ., 40 days, during which time none of the patients report­ I- 38 ed any spontaneous tooth pain. Histologic examina­ tion of the teeth failed to demonstrate any signs of 36 inflammation or reparative dentin. 34 Similar in vitro studies27 were done on extracted 0 5 10 15 20 25 30 35 40 human teeth with thermocouples placed at the pulp­ Time (s) odentin border, immersed to the cementoenamel Fig 15-3 Increases in pulpal temperature following a variety of experimental junction in 37°C. When the same electric currents procedures. (Modified from Baldissara et al27 with permission.) were applied to the teeth in vitro, the authors could follow the rate and duration of changes in pulpal temperature (see Fig 15-3). This study concluded that young premolars could withstand increases in pulpal temperature between 8.9°C and 14.7°C with­ 3.4°C. This resulted in 36.4% and 33.4% reductions, out any histologic evidence of pulpal damage. Their respectively, in cell metabolism as measured by the rate of heat application was less than that used in 3-(4,5-d i methylthi azol-2-yl)-2,5-d i p he nyltetrazo Ii um the studies by Zach and Cohen.7·10 Thus, the rate of bromide (MTT) assay. The authors concluded that a delivery of heat is probably more important than the quartz tungsten halogen curing unit activated for 40 absolute rise in pulpal temperature. seconds could cause adverse cellular responses in This temperature range is similar to that mea­ 0.5-mm-thick dentin.36-37 sured in pulp chambers during finishing or polishing The reader is referred to a recent review on heat of restorations.28 Even higher increases in pulpal transfer in human teeth38 for further details. temperature have been measured during self-curing of provisional crowns28-30 and from visible light­ cured crowns.31 These studies were repeated using the turbo tips that concentrate light on smaller sur­ Pulpal Responses to Mechanical faces32 and new high-intensity light sources,32·33 with Stimuli During Cavity Preparation similar results. Some authors believe that in vitro studies of pulpal temperatures in response to various thermal Several studies have reported on the release of stimuli should be done while the pulp chamber is enzymes and other immunoreactive substances in perfused by fluid to simulate pulpal microcircula­ the dental pulp during mechanical tooth prepara­ tion. A recent study confirmed that perfusion of the tion procedures. The release of these substances pulp chamber significantly lowered the pulpal tem­ may be due to temperature increases, the mechani­ perature increases in response to external thermal cal stimuli of tooth preparation, or both. Because stimuli34 as well as to light-curing units.35 temperature effects have already been discussed, An in vitro experiment involved the use of 0.5- this section reviews only the mechanical, nonthermal mm dentin disks covered on their pulp surfaces causes of release of these substances. by odontoblast-like cells. When the investigators Many enzymes and other immunoreactive sub­ irradiated the upper dentin surface with a quartz stances are normally present in the pulp under tungsten halogen or a light-emitting diode (LED) unstimulated conditions. When the pulp is stimulated light-curing unit at 553 and 240 mW/cm2, respective­ mechanically, these substances are released by physi­ ly, the "pulp" surface temperature rose 6.4°C and ologic mechanisms (eg, exocytosis) or by disruption

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of cell membranes.39 An early study in monkey teeth was found in all pulp specimens but in only 25% examined the effect of cavity preparation on enzyme of dentin specimens. The results indicated varying release (alkaline and acid phosphatases and others) responses of plasma protein release in reaction to in the pulp.40 Tooth preparation by air turbine and mechanical injuries. adequate water cooling did not affect enzyme activ­ Another study examined changes in the distribu­ ity, nor did the application of corticosteroids. When tion of fibrinogen/fibrin and fibronectin in the pulpo­ calcium hydroxide was applied to the cavity floor, dentin complex after Class V cavity preparation in however, enzyme activity was increased after 24 hours maxillary rat molars.44 Fibrinogen was detected in in the odontoblastic and subodontoblastic cell layers the exudate and dentinal tubules at various times adjacent to the calcium hydroxide-covered dentin. after preparation. Fibronectin staining showed a Fifteen days later, slight dentin formation was found, similar pattern in the exudate. At 3 days, the irregu­ possibly indicating a role for these enzymes in stimu­ larly shaped dentin under the preparation showed lating hard tissue formation.40 strong fibronectin staining. The results indicated Neuropeptides such as substance P and calci­ that these substances are present during the healing tonin gene-related peptide are present in dental process after mechanical injury. pulp in relatively high concentrations (see chapters Mechanically induced injury to the dental pulp 7 and 8). Rat molar dentin was prepared with a elicits a number of responses of immunocom­ high-speed handpiece and bur to determine injury­ petent Class II major histocompatibility complex related changes in the levels of immunoreactivity of (MHC) antigen-expressing cells (see chapters 6, both of these substances.41 Pu/pal exposures caused 10, and 11). Cavity preparations in rat maxillary first massive decreases in immunoreactive substance P molars caused an acute edematous reaction between (10% of baseline levels) and moderate decreases in injured odontoblasts and the predentin, and most immunoreactive calcitonin gene-related peptide of the OX6-immunopositive cells normally present in (45% of baseline levels) because of the destruction uninjured teeth shifted away from the pulpodentin of nerves that are the source of these neuropep­ junction.45 At 24 to 72 hours after injury, many of these tides. Preparation and acid etching without expo­ cells accumulated along this border and newly differ­ sure caused decreases of 10% to 20% and 60%, entiated odontoblasts appeared, indicating that Class respectively, of baseline levels. This study indicated II MHC antigen-expressing cells in the pulp partici­ that pulpal neuropeptides undergo dynamic injury­ pate in the initial defense reaction and may serve as a and peptide-specific responses following pulpal biologic sensor for external stimuli. Collectively, these trauma (see chapters 7 and 8). studies indicate that substances and cells normally Other changes may occur in the trigeminal gan­ found in healthy dental pulp play a role in events glion (see chapter 8). For example, dental injuries occurring when the pulp is adversely stimulated. affect the presence and distribution of neuropep­ A later study measured the response of OX6+ tide Y-like immunoreactivity.42 In normal trigeminal and ED1 + cells (Class II MHC cells) and macro­ ganglion, some perivascular nerves displayed neuro­ phages to mechanical preparation and a resin bond­ peptide Y-like immunoreactivity, but there were no ing agent.46 Preparations were made and immedi­ immunoreactive ganglionic cells. After dental injury ately restored in maxillary rat molars; unrestored and (extraction and pulpal exposure), neuropeptide Y­ nontreated teeth served as positive and negative like immunoreactive cells appeared in the ganglion, controls. The teeth were evaluated at 3 and 28 days indicating a change in the primary sensory neurons posttreatment using anti-Class II antisera (OX6) and of the ganglion. antimacrophage antisera (ED1 ). At 3 days, densities When dentin is exposed, plasma proteins such of both cells were significantly higher in the restored as albumin, immunoglobulin G, and fibrinogen are teeth than in the intact group. At 28 days, sound released by the process of plasma extravasation reparative dentin was observed, and the density of (see chapter 6). The concentrations of these plasma immunocompetent cells was comparable to that of proteins in dentinal fluid were compared to rela­ the intact teeth. Pu/pal abscesses were observed in tive concentrations of these proteins in the dental 14 of the 16 specimens in the teeth without resin, pulp.43 Albumin and immunoglobulin G were found indicating that the resin bonding agent reduced in all dentin specimens and were similar to fluid transdentinal antigenic challenges. specimens from exposed pulp tissue. Fibrinogen

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A report of the behavior of thick slices of human macNOS but no discernible nNOS reactivity. Similar dentin prepared immediately after extraction changes were seen around the inflamed areas. The attempted to develop a model correlated to tissue results indicate a role for nitric oxide in mediating healing.47 This study showed that the damaged pulp pulpal inflammation after an injury. beneath the preparation demonstrated cell prolif­ Odontoblasts are formative cells that are respon­ eration, neovascularization, and the presence of func­ sible for dentin matrix formation and mineralization. tional cuboidal cells close to the injured area. After Studies indicate that they display dynamic responses 30 days of culture, elongated spindle-shaped cells to injurious mechanical stimuli. Recent studies have were aligned along the edges of the prepared dentin, examined injury to the pulp cells responsible for which may indicate the formation of odontoblasts and hard tissue formation. One study measured the the onset of odontogenesis. This model may be use­ changes in odontoblast cell numbers in response ful for testing factors that regulate pulp repair. to injury with respect to cavity restoration variables Bone morphogenetic proteins affect the differ­ and patient factors and the effect those factors had entiation of pulp cells to odontoblast-like cells after on tertiary dentin repair.ss Class V cavity prepara­ injury during reparative dentinogenesis (see chapter tions and restorations were placed in premolars of 2). The effect of bone morphogenetic proteins on patients between the ages of 9 and 17 years. After the expression of nuclear proto-oncogenes (c-Jun removal of the teeth (28 to 163 days later), the area and Jun B) was evaluated after injury and during of reactionary dentin and the area of the odonto­ repair in rat molars.48.49 While both are coexpressed blasts were measured histomorphometrically. in tooth germs, only c-Jun was expressed in the Only the age of the subject appeared to have an odontoblastic layer of adult molars, whereas Jun B effect on odontoblast dentinal secretory capacity; expression was absent in all pulp cells. After injury, the older subjects demonstrated fewer odontoblasts both were coexpressed in cells beneath cavities, and per unit area.ss The area of reactionary dentin forma­ their levels greatly increased during early repair. At tion increased in proportion to subject age. Because 14 days, both were seen only in pulp cells lining the preparations were made in deep dentin and 0.5 mm surface of thick reparative dentin. The results indi­ of dentin was left over the pulp, the repair capacity cate a role for active formation of dentin matrix dur­ of the pulpodentin complex would appear to be age ing primary and reparative dentinogenesis. Cavity dependent. preparation in rat molars also causes relocalization A companion study found that RDT was the one of cytoplasmic heat shock protein 70 (HSP70) from variable determining reactive dentin formation.56 An the cytoplasm to the nucleus. HSP70 is thought to RDT of less than 0.25 mm caused a 23% decrease prevent apoptosis.SO-s2 Others have reported a vari­ in odontoblasts, and minimal reactionary dentin ety of HSPs expressed in human dental pulps.s3 repair was observed. The use of rat incisor slices Several other chemical mediators are released maintained in organ culture allows evaluation of during pulpal injury. Nitric oxide, produced by nitric operative variables on pulpal viability beneath Class oxide synthase (NOS; several isozymes have been V cavities.s7 The authors of that study confirmed that discovered; see chapter 11), has been implicated RDT was of paramount importance in protecting the in multiple inflammatory processes, and the level pulp from operative trauma, followed by bur speed of NOS can be used as a marker of tooth pulpal and smear layer removal, but not restorative mate­ insult. Therefore, relative distributions of NOS in rials8 (see chapter 14). uninflamed and inflamed rat pulps were examined.54 It is apparent from these studies that multiple Tissue levels of both macrophage NOS (macNOS) levels of responses and interactions occur in reaction and neuronal NOS (nNOS) in normal and inflamed to mechanical injuries of the dental pulp. Responses rat molar pulp were determined at multiple time include inflammatory changes mediated by release points. Deep cavity preparation produced a time­ of various neuropeptides and changes that are dependent inflammatory response that was acute defensive in nature and responsible for genesis of early, later progressing to a chronic, granulomatous new hard tissue to replace the tissue injured by car­ response with necrosis and spreading down the ies and typically removed by traumatic methods. The root adjacent to the preparation. Unprepared teeth pulp is a complex tissue that reacts much as other showed a faint homogenous distribution of nico­ body tissues react and must be protected in its envi­ tinamide adenine dinucleotide phosphate-d and ronment to extend the life of the tooth.

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Responses to Thermoplasticized small size of the heat carriers used with that tech­ nique. However, external root temperatures mea­ Gutta-Percha Obturation sured by infrared thermogravic cameras were sig­ Techniques nificantly higher than temperatures measured with thermocouples in the same teeth in vitro.66 In vivo studies of the histologic response of the PDL and The clinical technique of warm vertical compaction surrounding bone to obturation with thermoplasti­ for obturation of root canals relies on a combination cized gutta-percha found little adverse response.68 of fortuitous properties. The high thermal conductiv­ Nevertheless, the 31°C increase reported by Fors et ity and low heat capacity of stainless steel (see Table al69 has made clinicians wary of potential periodontal 15-1) means that it can be rapidly heated and can injury. deliver that heat quickly. This permits thermoplastici­ Is there any danger that the high internal root zation of gutta-percha, thereby softening it, lowering temperature produced by thermomechanical com­ its stiffness,59·60 reducing its viscosity, and allowing it paction can weaken root dentin? The apparent to flow within a cylinder made up of a good thermal "thermal contraction" reported5 to occur above insulator (ie, root dentin). The use of metallic carri­ 55°C to 60°C should not be interpreted as being ers at temperatures heated to 321°C61 would seem due to thermal denaturation of collagen in the min­ extreme, but the mass (and hence the specific heat) eralized matrix. The denaturation temperatures of of stainless steel times the mass of the metallic heat mineralized dentin (hydrated versus dehydrated) carrier determines how many calories of heat energy are shown in Fig 15-4. In these experiments, small can be transferred to the root canal. pieces of dentin were sealed in small pans that were The development of the split-root model con­ placed in a calorimeter within an oven. As the oven taining an array of 16 thermocouples has provided temperature increased from 25°C to 200°C, the heat a convenient method for evaluating changes in flow between an empty reference pan and the pan pulpal and periodontal surface temperatures during containing dentin was measured. When collagen various endodontic procedures.62 The introduction denatured (ie, when highly structured linear collagen of electrically heated carriers such as the Touch 'N was converted to random coils of gelatin), heat was Heat (SybronEndo) and the System B (SybronEndo) absorbed and produced a peak in the differential has made it much more convenient to deliver large scanning calorimeter tracing.70 amounts of heat to gutta-percha in the root canal Hydrated mineralized dentin does not denature space. These devices can generate tip temperatures until the temperature of dentin reaches 170.4°C (see between 250°C and 600°C. There was concern that Fig 15-4). Dehydrated dentin requires even higher such high temperatures could cause thermal dam­ temperatures to denature (186.5°C).71 Completely age to periodontal63 and periapical tissuesM·65 How­ demineralized, fully hydrated dentin matrix dena­ ever, when the temperature at the external surface tures at 65.5°C. While this is similar to the thermal of the root was measured over an intracanal tem­ contraction reported in roots by Kishen and Asundi,5 perature range of 200°C to 600°C (using a System B their dentin was fully mineralized. The apparent heat source), the measured increases in root surface contraction that they reported is due to the unique temperature were only 1.04°C to 5.78°C, regardless structure of dentin and the manner in which those of the internal root temperature. The authors specu­ measurements were made. lated that this resulted from brief but profound heat The differential scanning calorimeter tracing mea­ loss from the hot gutta-percha back up to the inacti­ surements of thermal denaturation have potential vated heat carrier that served as a heat sink.65 implications in endodontics. Although heat sources The use of heat to plasticize gutta-percha dur­ such as System B produce tip temperatures of 200°C ing obturation of root canals raises the risk of over­ to 300°C, the presence of gutta-percha and sealer heating the PDL66 or the surrounding bone.67 The between the heat source and the dentin may protect warm vertical condensation technique was shown to the dentin from exceeding the thermal denaturation increase apical temperature by only 4.0°C and cervi­ temperature (177°C) of mineralized, hydrated, old cal temperatures by only 12.5°C in an in vitro study.67 root dentin (see Fig 15-4). As soon as the heat source These low temperatures were probably due to the is turned off, the heat flow reverses and travels back low thermal conductivity of gutta-percha and the up the metal tip into the heating device. Only if the

356 www.shayanNemodar.com Responses to Thermoplasticized Gutta-Percha Obturation Techniques

250

p 200 !!! E "'� 150 c. E 2! c: 0 100 .., "'

..,:; "' c � 50

0 Hydrated Dehydrated Hydrated Hydrated Fully Intermediate Low Very low young young young root old root hydrated hydration II hydration Ill hydration IV coronal coronal dentin dentin Fig 15-4 Denaturation temperatures (°C) of mineralized and dentin dentin demineralized dentin. Bars identified by different lowercase � letters are significantly different (P < .05). (Modified from Arm­ 1---- Mineralized dentin Oemineralized dentin ---1 strong et al7° with permission.)

activated hot tip touched the dentin wall of the root However, more recent work indicates that deminer­ canal could it deliver enough heat to have the poten­ alized dentin that has been infiltrated with adhesive tial to denature dentin collagen. resins (and perhaps resin-based endodontic sealers) However, if the root canal treatment involves the is protected from thermal denaturation.71.72 Dena­ use of acidic agents such as BioPure MTAD irrigant tured insoluble collagen becomes soluble gelatin (Dentsply Tulsa Dental), the mineral phase of the and may slowly dissolve, leaving a 10-µm-wide gap root dentin is removed to a depth of 10 µm.72 This between the underlying mineralized dentin and the completely demineralized dentin can denature at root canal filling material. a temperature of 66°C if the demineralized matrix Although these temperatures would appear to is hydrated. Although endodontists attempt to dry be sufficient to cause irreversible damage to the root canals prior to filling, one study indicated that PDL and bone, endodontists report anecdotally few use of one or two paper points is not sufficient to adverse incidents occurring with the use of gutta­ really dry the apical third of the canal.73 An alterna­ percha heating devices or gutta-percha placed by tive approach is to remove the water with ethanol.74 obturators or plasticizing guns. It appears that a tem­ Because the denaturation temperature of demineral­ perature rise of 10°C or less can be tolerated for ized dentin is highly dependent on its state of hydra­ short periods of time (less than 1 minute) without tion, much more research is needed to determine irreversible damage to the PDL or bone. The intro­ the optimum conditions and techniques for adhesive duction of heat delivery devices and low-temperature endodontics if acidic irrigants are to be used. thermoplasticized gutta-percha delivered by the gutta­ Numerous studies of the internal temperature of percha delivery guns seems to ensure that tempera­ the root canal's dentin surface revealed temperature ture rises will be low enough to avoid damage to increases of 45°C to 85°C when thermal obturation adjacent soft and hard tissues (PDL and bone). techniques were used.75 If the initial temperature is Temperatures recorded at the midroot of canines 34°C, the intracanal dentin temperatures could be during thermomechanical compaction of gutta­ between 82°C and 122°C. The frictional heat gener­ percha revealed no statistically significant differ­ ated by thermomechanical compaction techniques ences between the elevation of temperatures in produced temperatures of 55°C to 75°C76 and 65°C vitro and in vivo. However, temperature elevations to 100°C within the root canal. These intracanal tem­ dissipated more rapidly in vivo, which was thought peratures are enough to denature any exposed col­ to result from the cooling effect of the microcircu­ lagen in predentin or any root canal dentin that has lation. The PDL temperatures that were recorded been acid etched (ie, treated with BioPure MTAD).72 were lower than the critical 10°C level.77 This is an

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important study because several other studies have generate higher temperatures, which may result in reported inconsistent findings about in vitro and in injury to the PDL and bone. vivo temperature differences measured on the outer Temperature changes during application of gutta­ root surface. When a System B device was tested percha, thermoplastic gutta-percha, and Resilon in vitro with temperatures recorded using a fine cones with a thermomechanical compactor were Buchanan plugger,78 temperatures were elevated measured. Significant differences between mean 2°C S mm from the apex but only 1°C at the apex. initial temperature increases (S°C) and maximum Extracted molars were mounted in an artificial PDL temperature increases (8°C) occurred with all mate­ and alveolar socket, and thermocouples were placed rials. Changes in temperatures were higher in the at the outer surface of the roots. Similar results, with apical third than in the cervical third of root canals.84 temperatures recorded through thermocouples, Ultrasonic compaction of gutta-percha has been found increased temperatures of O.S°C to 4.1°C.78 suggested as an alternative to use of heat-generating Questions as to the accuracy of thermocouples devices that can be used to soften materials such as in comparison to thermographic assessment of root the newer thermoplastic resins (eg, Resilon). When surface temperatures have led to testing of obtura­ different power settings (1, 3, or S) and durations of tion techniques. An infrared thermography camera activation (4, 10, or 1 S seconds) were used to test was used to measure external root surface tem­ temperature rise at the root surface, the combination peratures during placement of Thermafil (Dentsply) of a setting of S and a 1S-second activation caused a gutta-percha on a carrier in extracted molars.79 Mean temperature rise greater than 10°C, above the critical temperature rises differed according to the root temperatures necessary to maintain healthy attach­ tested and ranged from 4.3°C to 4.9°C. When four ment tissues.85 Furthermore, a case report described different gutta-percha obturation techniques were severe damage to alveolar bone, gingiva, and nasal evaluated (carrier or injection application) with a mucosa.86 Overheating caused necrosis of soft tissue thermal imaging camera,80 temperature rises exter­ and bone on two surfaces of a maxillary central incisor nally were 2.0°C for injected- and 3.7°C to 3.9°C for and an inflammatory response in the adjacent cavity carrier-applied gutta-percha. Both applications were after the use of an ultrasonic packing regimen. This described as low-temperature gutta-percha. event reinforces the need to reassess ultrasonic use in A later study81 used a high-temperature injectable root canal obturation procedures.86 technique to test external root temperatures in vivo Some endodontic techniques aim to pack root and found temperature increases ranging from 8.S°C canal systems in a process that results in a three­ to 22.0°C; the lower temperatures were found in thin­ dimensional fill through the entire length of the ner maxillary central incisors and the higher elevations system. It is important that the operator understand in the mandibular incisors. Certainly, the thickness of that materials requiring use of high temperatures hard tooth structure is important, as is the microvas­ may cause PDL and bone damage. Awareness of the culature present around intact, treated teeth. research findings in this area should decrease the A more recent study utilized finite element analy­ potential for thermal damage. sis to determine the distribution and temperature rise in a model of a maxillary canine, surrounding PDL, and bone during a System B obturation simu­ lation.82 Heat applications of 100.0°C and 200.0°C Thermal Responses to Laser were considered. The maximum predicted tempera­ Treatment ture at the PDL was 43.S°C, which would have cre­ ated no harmful temperature effects. Lipski and Wo:Zniak,83 using an infrared thermal The search for alternative methods to remove enam­ imaging camera, recorded temperatures when Sys­ el and dentin has led to the development of tech­ tem B was used to retrieve Thermafil gutta-percha niques such as lasers and air abrasion devices. The and obturators from treated, extracted teeth. They word laser is an acronym for light amplification by recorded temperatures that ranged from near 28°C the stimulated emission of radiation. Dental lasers to 46°C. This may be of some concern in retreat­ used today for clinical procedures and research ment, when obturation material is to be retrieved. It operate at the infrared, visible, or ultraviolet (UV) would appear that these types of cases require and range of the electromagnetic spectrum (Figs 1 S-S

358 www.shayanNemodar.com Thermal Responses to Laser Treatment

Fig 15-5 Wavelengths of different types of laser according to their emission KTP Alexandrite Holmium C02 spectrum. Laser types differ in wavelength, beam characteristics, and available energies. KTP, potassium-titanyl-phosphate. (Courtesy of Opus Dent.) Nd:YAG Er:YAG

Infrared

400 nm 700 nm

Reflection Scattering

Absorption

Fig 15-6 Diagram of a laser.

Fig 15-7 Four basic types of laser interaction that occur when light hits matter or tissue: reflection, scattering, transmission, and absorption. (Courtesy of Opus Dent.) and 15-6). While I stands for light, the actual physical Laser photons interact with tissue in one of four process that occurs within a laser device is amplifica­ general ways: they are (1) transmitted through tissue, tion by stimulated emission of radiation. The laser (2) reflected from tissue, (3) scattered within tissue, beam (restimulated emission of radiation) differs or (4) absorbed by tissue (Fig 15-7). Transmission of from conventional light sources in three ways: (1) It light passes energy through the tissue without inter­ is a single wavelength (monochromatic); (2) it is colli­ action and thus causes no effect or injury. Reflection mated (very low divergence); and (3) the photons are of laser photons allows little interaction between the in phase (referred to as coherence). laser energy and the substrate and hence causes The medium producing the beam is what identi­ no effect or injury. When scattered, light travels in fies the laser and distinguishes one from another. different directions and energy is absorbed over a Different types of lasers used in dentistry, such as greater surface area, producing a less intense and carbon dioxide (C02), erbium (Er), and neodymium less precise thermal effect. When absorbed, light (Nd), various other substances used in the medium energy is converted into thermal energy. In general, (eg, yttrium-aluminum-garnet [YAG] and yttrium­ a single laser device cannot perform all possible scandium-gallium-garnet [YSGG]), and argon, diode, functions because the beam is absorbed or reflected and excimer types all produce light of a specific according to its wavelength and the color of the wavelength. The C02, Er:YAG, and Nd:YAG lasers object impacted. emit invisible beams in the infrared range. These Different laser wavelengths affect biologic tissue lasers are coupled with a nonabsorbing light source in different ways. In other words, there is no one laser (often red, green, or white) that serves as a pointer wavelength that can be utilized to deliver various for the working laser. The argon laser emits a vis­ modalities of dental care. Some wavelengths are use­ ible light beam at either 488 or 514 nm, while the ful and efficient in creating tooth preparations (hard excimer lasers emit invisible UV light beams at vari­ tissue applications in enamel and dentin), while other ous predetermined wavelengths (see Fig 15-5). wavelengths are more effective when used for soft

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•Drill safety. The clinician controls four parameters when * 0.3-W, 10-Hz laser operating the laser: (1) the level of applied power + 0. 5-W, 10-Hz laser (power density), (2) the total energy delivered over a ... 0.7-W, 10-Hz laser 20 given surface area (energy density), (3) the rate and 0 & 1.0-W, 10-Hz laser � duration of the exposure (pulse repetition), and (4) QI 15 ·� the mode of delivery of the energy to the target tis­ � :I 10 sue (ie, continuous versus pulsed energy and direct ...

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Numerous studies have evaluated the effects of gy produced complete pulpal necrosis at 3 days, lasers on enamel and dentin. Under certain condi­ while 3S J produced pulpal inflammation that was tions, use of lasers increases the acid resistance of reversible in some cases.108 In the first report of a enamel or dentin. Thus, it is not surprising to find that laser application in humans, two 1-millisecond puls­ laser-treated dentin may produce lower resin-dentin es of 17 J produced no pain sensation in spite of the bond strengths than untreated acid-etched dentin.99•100 destruction of some enamel.109 In a comprehensive Several lasers have been used inside root canals study on ruby lasers applied to dog incisors, it was to clean and shape the canal, to remove smear concluded that the amount of energy required for layers, or to sterilize the canal.101-103 There are sev­ hard tissue removal caused pulpal necrosis, leading eral limitations to intracanal use of lasers: The light the investigators to consider alternative therapies.110 is emitted at the end of the light guide instead of the side; the light guide must be very small (approxi­ C02 lasers mately a.2 mm), and it must be stiff but not brittle co2 lasers represent an alternative to ruby lasers to permit easy manipulation within the canal. It is because the infrared wavelength produces signifi­ almost impossible to obtain uniform coverage of the cantly different thermal effects, permitting fusion of canal surface using a laser. Further, bacteria often pits and fissures, conversion of carbonated apatite invade the tubules and remain viable below the sur­ to the more insoluble calcium orthophosphate, stim­ face, where they can multiply back into the canal. ulation of new dentin formation, and reduced pulpal The potential for thermal damage to the peri­ responses.111·112 In a study measuring hydraulic con­ apical tissues remains a concern with lasers oper­ ductance across dentin disks, co2 lasers increased ated in the nanosecond to millisecond pulse widths. dentin permeability 1.4- to 24.a-fold by such mecha­ The intracanal use of a potassium-titanyl-phosphate nisms as removal of smear layer and smear plugs, (KTP)-S32 laser (an Nd:YAG beam passed through cratering, and cracking in the glazed surface of the a potassium titanyl phosphate crystal to change the crater113·114 (Figs 1 S-9 and 1 S-1a). However, there is a wavelength from invisible infrared to visible green major limitation to the C02 laser: When used to pre­ light) increased the permeability of ethylenediamine­ pare cavities, it creates severe thermal damage to tetraacetic acid-etched root dentin by removing dentin due to the strong absorption of the emitted organic material, as was definitively shown by the photons by water114 (Fig 1 S-11 ). In a clinical trial with elegant Fourier transform infrared photoacous­ co2 lasers, the increase in pulpal temperature never tic spectroscopy studies of Spencer et al.104 The exceeded 1 a.S°C, although the odontoblast destruc­ authors used pulse widths of a.2 to 1.a second. tion was inversely related to remaining dentinal When pulse widths were decreased to 1aa picosec­ thickness.115 Others have demonstrated that as little onds, Serafetinides et al105 obtained very different as 3.S J of co2 laser irradiation may produce pulpal results with the same wavelength laser; thermal damage in vivo, and concern has been raised about damage was minimized. Even less thermal dam­ using levels as low as 1.a J.116 age was obtained at 1,a64 nm for 1 aa-picosecond To adapt C02 lasers to the needs of dentists, pulses, confirming the earlier work of Willms et al.106 co2 wavelengths have been tested in an effort to Similar impressive results were reported by Niemz et find a wavelength that would allow its use without al,94 who used a 1,a3a-nm laser with pulse durations causing damage to the soft tissue core of a tooth. of less than saa femtoseconds to lower heat transfer A high-pulse rate C02 laser designed for soft tis­ to dentin. sue surgery was tested for its effects on dental hard tissue.117 Pulpal temperatures ranged from a.S°C to 19.a0C. At cumulative fluences of 4a J/cm2, 2aa Laser types pulses/s and higher caused measurable hard tissue loss, indicating that there were threshold conditions Ruby lasers above which a pulsed co2 laser would cause hard Ruby lasers, one of the first types of laser used in tissue damage. Two 9.6-µm wavelength C02 lasers dentistry, produced cratering in enamel, particularly caused no pulpal damage at 4 days and 4 weeks at higher energy densities or when applied to dark postirradiation in dog canines.118 Using healthy or carious enamel.107 In one study of the use of ruby human molars in situ, Nair et al119 found no pulpal lasers on hamster teeth, application of SS J of ener- damage at 7 days or 3 months after laser applica-

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Fig 15-9 Scanning electron micrograph (SEM) of Fig 15-10 SEM of C01-irradiated dentin at an Fig 15-11 SEM of C01-irradiated dentin at an ener­ COi-irradiated dentin at an energy density of 113 Ji energy density of 566 J/cm1. Most of the crater sur- gy density of 11 J/cm1 showing a single-impact crater. cm2. Much of the crater wall appears to be glazed, face is glazed, although numerous pits remain. The Large cracks were not present when the hydraulic but the floor is covered with pits (original magnifica- inner halo is devoid of smear layer or smear plugs; conductance of the specimen was measured (original tion x 100). (Reprinted from Pashley et al11' with the outer halo shows more tubule occlusion (original magnification x 100). (Reprinted from Pashley et al"' permission.) magnification x 120). (Reprinted from Pashley et al'" with permission.) with permission.)

Fig 15-12 (a) Er:YAG laser cavity preparation in dentin in monkey teeth (hematoxylin-eosin stain; original magnification x 40). (b) C01 laser cavity preparation in dentin in monkey teeth (hematoxylin­ eosin stain; original magnification x 25).

tion. The use of a transversely excited atmospheric 350 microseconds, water cooling limited increases in pressure, 9.6-µm wavelength co2 laser produced pulpal temperatures to less than 3.5°C when Class I no permanent pulpal sequelae at 1 week to 1 month and Class V cavities were prepared. after the procedure.120 This same wavelength was However, when Er:YAG-treated dentin (180 mJ, also used to produce an enamel surface that was 2 Hz, 250-microsecond pulse duration with water resistant to acid dissolution,121 to remove carious cooling) was examined by transmission electron dental hard tissue and prepare cavities, and to pre­ microscopy, the hybrid layer created by bonding vent caries by sealing the surface pits and tissues of with a dentin adhesive appeared badly damaged126 partially erupted third molars.122 (Fig 15-13). Collagen fibrils located at the surface of the hybrid layer were partially vaporized, and the Er:YAG lasers remaining fibrils were fused together to produce Several studies have evaluated the properties of the crustl ike features (Fig 15-14). Because peritubular Er:YAG laser. The depth and diameter of Er:YAG dentin contains no collagen and is more highly min­ laser-drilled holes are a function of pulse number eralized, the fibrils appeared as a peripheral mineral and the amount of exposure to energy parameters.123 ring around resin tags, with a free space that was left Using various wavelengths, Wigdor et al124 compared after vaporization of the adjacent collagen-rich inter­ the histologic response of the dental pulp to dentinal tubular dentin (Fig 15-15). Even the collagen fibrils Er:YAG laser ablation in dog teeth and suggested beneath the hybrid later exhibited a variable degree that the thermal effect might be less than that of the of damage, ranging from fusion of collagen fibrils to other lasers tested. Goodis et al found that, when a disintegrated mass that was devoid of interfibrillar used in cavity preparation, the Er:YAG produced no spaces to unraveling of the microfibrillar elements detectable pulpal damage at energy levels of 3W of the grossly denatured collagen fibrils to the loss and 10 to 30 Hz (unpublished data, 2003) (Fig 15-12). of cross banding on structurally intact fibrils (Fig Even when Oelgiesser et al125 used the maximum 15-16). Resin-dentin bonds in such dentin had very laser energy of 12 W at 12 Hz with a pulse width of low bond strengths compared to bonds in control

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Fig 15-13 Transmission electron micrograph of Er:YAG laser-treated dentin Fig 15-14 Higher-magnification image of the surface of the structurally that was acid-etched after laser application and bonded with Single Bond degraded hybrid layer after the application of Single Bond adhesive to acid­ adhesive (A). This low-magnification image of the resin-dentin interface shows a etched, laser-ablated coronal dentin. The laser has melted the collagen fibrils, 3- to 5-µm-thick laser-modified layer (L) that has separated from the underlying which have fused together to produce platelike elements (arrow) that are intertubular dentin (D). There was incomplete infiltration of resin (dark staining partially infiltrated by the electron-dense, polyalkenoic acid copolymer (P) material on the surface) into the laser-modified layer because the collagen fibrils component of the dentin adhesive (A). An electron-lucent resin tag (T) within a had become fused together, thereby eliminating the interfibrillar spaces that dentinal tubule is surrounded by a peripheral layer of peritubular dentin (see Fig normally serve as diffusion channels for resin infiltration. The resultant space 15-15). (Courtesy of Dr Franklin Tay, Augusta, GA.) (S) has been infiltrated by the laboratory embedding resin. Remnant resin tags (arrow) can be seen within the laser-modified layer. (Courtesy of Dr Franklin Tay, Augusta, GA.)

Fig 15-15 High-magnification view of the basal portion of the laser-modified 'Fig 15-16 Stained, laboratory-demineralized intertubular dentin beneath hybrid layer. Collagen fibrils from the base of the hybrid layer have completely the hybrid layer of laser-ablated resin-bonded dentin. Laser ablation has cre­ disappeared and are replaced by the laboratory epoxy resin (Ep). Because ated structural damage to the mineralized intertubular dentin that is far deeper peritubular dentin is devoid of collagen and is more highly mineralized, it is not than the depth of the hybrid layer (usually 3 to 5 µm thick), although this badly vaporized completely after laser treatment. Infiltration of the adhesive through damaged collagen matrix was still protected by minerals. When the apatite a dentinal tubule (T) has resulted in the retention of a peripheral ring of resin­ minerals are removed by laboratory demineralization agents, the surface of the encapsulated peritubular dentin (open arrowhead) around the resin tag. The mineralized dentin base (ie, adjacent to the base of the hybrid layer) appears mineralized dentin base beneath the hybrid layer also exhibits extensive dam­ amorphous, with the degraded gelatin melted into a fused, structureless mass age after laser ablation. This mineralized layer had been demineralized during (asterisk). A few remnant intact collagen fibrils are visible (open arrowhead), laboratory specimen preparation, enabling the structural components of the although these fibrils do not exhibit any cross banding. This means that those stained collagen matrix to be identified. Collagen fibrils from the most super­ collagen fibrils had already been denatured by the heat generated during laser ficial part of the mineralized dentin base have completely melted and fused ablation. The rest of the collagen fibrils have been broken down into their together, producing a layer that is completely devoid of interfibrillar spaces microfibrillar components (arrow), producing regions that contain only gelatin. (asterisk). Beneath this fused layer, the intertubular dentin (D) is also denatured. (Courtesy of Dr Franklin Tay, Augusta, GA.) No cross banding can be observed from the collagen fibrils. (Courtesy of Dr Franklin Tay, Augusta, GA.)

acid-etched dentin. Based on these ultrastructural Too often, investigators rely only on scanning observations, the damage created by laser ablation electron microscopy to evaluate the effect of lasers contraindicates its use as an adjunctive treatment in on dental hard tissues. Although this technique dentin bonding. has served well, it provides little subsurface detail

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of potential damage. More transmission electron human third molars, concluded that the Er:YAG micrographic studies should be done in the future. laser at a 2.94-µm wavelength would cause little, if There are many procedures used in the practice any, pulpal damage when specific energy settings of dentistry, and it is not surprising that laser energy were used. Other studies have concluded that the has been suggested for some of those procedures. Er:YAG wavelength is a reasonable alternative to tur­ However, because of the cost of laser devices, den­ bine handpieces when used with water cooling.131•132 tists would prefer to be able to use the device for Theodora et al133 compared the erbium to a diode several different procedures. As previously stated, laser in generation of heat on root surfaces when a single wavelength may be effective for a particular the devices were used for scaling. Recorded pulpal procedure but not for other procedures. There are temperatures were well below the level (10°C) that several different applications for which lasers have would cause irreversible pulpal problems. been advocated. Many of the studies cited in the previous para­ In 1997, the US Food and Drug Administration graphs tested Er:YAG lasers in extracted teeth and approved the use of the Er:YAG laser for caries only measured pulpal temperatures. Complete eval­ removal, tooth preparations, and modification of den­ uation of these devices requires the use of in vivo tin and enamel. As to pulp tissue effects, the Er:YAG studies to compare laser energy to conventional laser and the turbine handpiece were judged to be tooth preparation methods using histopathologic equivalent.127 However, a general impression among and immunohistochemical studies of the effects clinicians is that the speed of preparation in dentin on pulpal nerves. When cavity preparations were and especially in enamel is much slower with the placed in rat molars in vivo, repair of nerve fibers Er:YAG laser than with the conventional high-speed was observed.134 Laser-treated molars demonstrated drill. a marked fibroblast cell proliferation and formation Maintenance of pulpal health during cavity prep­ of more reparative dentin than was seen when com­ aration is a critical requirement to be able to utilize pared to molars prepared with a high-speed hand­ laser energy in hard tissue removal in vital teeth. piece. Increased levels of calcitonin gene-related During tooth preparation procedures, both lasers peptide fibers were also observed earlier than in and high-speed handpieces generate heat, which, conventional high-speed handpiece preparations, without proper cooling, can cause pulpal tempera­ but levels returned to normal at 7 days. The result tures to rise to a level where irreversible pulpal suggests that use of Er:YAG laser energy leads to damage occurs. To this end, several studies have pulpal repair earlier than that which occurs following compared the use of the Er:YAG wavelength to the use of a high-speed turbine handpiece. handpieces. Class V cavities were placed in 28 teeth Similar results were found when maxillary molars of a female baboon.128 Fourteen teeth in two quad­ were used to evaluate the role of immunocompetent rants were prepared conventionally (handpiece}, cells and expression of HSP25.135 Rat molars were while 14 other teeth in the remaining two quad­ examined after tooth preparation or replantation.136 rants were prepared with the Er:YAG laser deliver­ They showed degeneration of odontoblasts with ing 500 mJ at 10 Hz and at a wavelength of 2.94 loss of HSP25 immunoreactions. Numerous Class II µm. At remaining dentinal thicknesses of 0.77 mm MHC-positive cells appeared along the pulp-dentin for the handpiece and 0.81 mm for the laser, most borders but disappeared by postoperative days 3 pulps appeared normal; one pulp in each group was to 5. Suzuki et al137 found that cavity preparation judged to be irreversibly damaged. caused destruction of odontoblasts and a shift of A similar study in bovine mandibular incisors Class II MHC-positive cells from the pulp-dentin found similar results between handpiece and laser border to the middle of the pulp. However, no effort when water cooling was used during the cutting was made to close the exposed dentinal tubules, preparations.129 The test group treated without and subsequent inflammatory events occurred due water cooling developed increases in pulpal tem­ to invasion of microorganisms, which delayed pulpal perature of 11.6°C. When pulpal temperatures were regeneration. measured in freshly extracted teeth during Class I Neural elements examined in rat pulps after and Class V cavity preparations, 124 the measured Er:YAG laser irradiation demonstrated disruption of temperature increases were well below the thresh­ nerve terminals in dentinal tubules, degeneration of old of 45°C.7 Nair and coworkers, 130 using healthy nerve terminals between odontoblasts, and disrup-

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tion of the myelin sheaths within the central pulp.138 trical pulp testing results increased in six patients This effect may lead to pain reduction with laser use. and decreased in six others; one patient showed no Other uses have been suggested for Er:YAG change. One month after laser treatment, all values lasers, including laser treatment of margins of Class returned to pretesting levels. Systemic blood pres­ V preparations to decrease microleakage.139 Others sure and pulse rate were not affected. found that laser intervention did not lessen micro­ In a pulpal study, laser-irradiated rat mandibular leakage.140 Delme et al141 found that cavity seals incisors showed a slight delay in eruption.148 Histo­ were dependent on the type of glass ionomer used. logically, reparative dentin formation was accompa­ nied by the formation of a layer of odontoblast-like Nd:YAG lasers cells in the damaged area. lmmunohistochemistry The lack of thermal damage but improved cutting studies revealed pulpal areas expressing transform­ efficiency of picosecond pulses of Nd:YAG laser ing growth factor �' which was judged to play a role irradiation is thought to be due to the fact that the in dentin regeneration. energy per single photon emission is only 1.18 elec­ tronvolts (eV), which is insufficient to break molecular Excimer lasers bonds or destroy ionic crystalline lattices. Nd:YAG Excimer lasers, which emit photons in the UV range, lasers were initially investigated using a contact offer the potential advantage of reduced heat mode. Other laser wavelengths (holmium, C02, and absorption and reduced dentin cracking. Both the erbium) could not be used in this mode. Manufactur­ argon-fluoride excimer (193 nm) and the xenon-chlo­ ers also developed a 100-µm-diameter light guide ride excimer (308 nm) laser melted dentin but did (equivalent in size to a No. 10 endodontic file). The not occlude dentinal tubules.149 Although perme­ studies above were representative of the early inves­ ability of the dentin was not measured, subsurface tigations into the neodymium wavelength. Interest deposits that may have reduced dentinal permeabil­ lessened as other manufacturers developed other ity were unlikely. wavelengths using "hot tips" to mimic tooth content The use of excimer lasers as a method for cut­ when used. Recently, clinical interest in the 1.06-µm ting enamel and dentin without generating excess Nd:YAG laser has grown. thermal stress looks very promising. Operating at Although the photon absorption of 1,064-nm 248 nm, the excimer laser can preferentially remove energy by dentin is low,142 Nd:YAG energy absorp­ intertubular dentin without creating a smear layer; tion by water is relatively high, allowing vaporization the dentinal surfaces are so clean that they appear to occur so rapidly as to create microexplosions that as if they were fractured150 (Fig 15-17). The photon cause mechanical ablation.117·142-144 According to energy in excimer lasers operating at 193 and 248 Niemz,145 mechanical disruption can be of two types. nm is higher than the molecular bond energies hold­ Plasma-mediated ablation results when the laser ing collagen together. This results in photoacoustic energy ionizes enough tissue components and heats destruction of dentin without melting. it to a plasma state, whereas a photodisruption type Reductions in the pulse length from millisecond of ablation is due largely to acoustical shockwaves to picosecond have been shown to reduce ther­ from rapid vaporization of water. mal damage caused by excimer, Nd:YAG,151 and Scan irradiation (movement of the laser contact neodymium:yttrium-lithium-fluoride lasers.152 It is probe across a tooth to cause an effect) was used to thought that picosecond pulse durations are less determine if the laser had any deleterious effects on than the thermal relaxation times of dentin, thus pulpal nerve activity and pulpal blood flow in cats.146 minimizing any thermal effects.153-155 The use of this 1,064-nm wavelength caused pulpal damage and decreases in compound acting poten­ tials to external stimuli and decreased the activity of Laser applications both single A8 and C fibers during irradiation. In a human study, pulpal blood flow, responsiveness to Treatment of dentinal sensitivity electrical pulp testing, systemic blood pressure, and Dentinal sensitivity continues to present problems pulse rate were recorded during Nd:YAG irradiation for patients who have undergone periodontal sur­ of an isolated tooth in 13 patients.147 While pulpal gery that may result in cervical exposure of root den­ blood flow increased during laser irradiation, elec- tinal tubules. Various treatment regimens have been

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Fig 15-17 (a) SEM of enamel irradiated with an excimer laser, revealing the precise removal of hard tissue at 248 nm with 15-nanosecond pulses. (b) SEM of dentin irradiated at 248 nm with an excimer laser used at 15-nanosecond pulse widths. (Reprint­ ed from Pearson and McDonald'5' with permission.)

advocated to reduce or eliminate cervical sensitiv­ test and control teeth at 1, 4, and 16 weeks, both ity, including placement of resins, glass ionomers, groups improved significantly from baseline to 16 varnishes, and other chemical solutions to close the weeks. When the morphologic changes of sensi­ dentinal tubules and halt movement of dentinal fluid tive cervical dentin were studied, impressions taken through the tubules. It is this fluid movement that before laser treatment displayed protrusive rods (an activates primary afferent nociceptors coursing in indication that the impression material had penetrat­ and around odontoblast processes and cell bodies. ed open tubules), while impressions taken after laser Two mechanisms have been proposed for laser­ treatment showed no protrusive rods.158 induced reduction in dentinal hypersensitivity. First, Other studies have demonstrated the efficacy lasers may occlude dentinal tubules by melting and of the Nd:YAG laser combined with 5% sodium fusing dentin or the smear layer or by coagulating fluoride.159 Those authors reported that the com­ proteins in dentinal tubules.153 Second, lasers may bined treatment occluded tubule orifices, and the directly reduce neuronal activity.142 same effect was noted by Hsu et al.160 The latter The use of laser energy to occlude tubule ori­ study found that the sodium fluoride crystals were fices by melting and resolidification of dentin alone "burned into" the tubules when tubular orifices or in combination with materials to achieve the melted and resolidified and could not be removed same result has been investigated to evaluate pos­ with normal brushing. sible irreversible pulpal reactions. The Nd:YAG laser Other studies have focused on the use of appears to be the device most studied for use in Nd:YAG lasers for desensitization of hypersensi­ treating dentinal sensitivity. A YAG laser was used tive teeth. In a 2-week clinical trial, hypersensitive with an energy output of 30 mJ, 10 Hz for 2 minutes teeth treated with Nd:YAG lasers were significant­ in 30 patients suffering from cervical hypersensitiv­ ly less sensitive to air blasts than were untreated ity.156 The patients were followed for 3 months, and control teeth.97 During treatment, the power was pulpal effects were assessed with mechanical and increased either until the patient detected the laser thermal stimuli. Results showed a 65% reduction in energy or until a maximum of 100 mJ was reached. sensitivity to air and a 72% reduction in sensitivity to While it is unlikely that this relatively low energy probing and no other adverse reactions. The same would have sealed exposed dentinal tubules, it group later compared sodium fluoride varnish and might have altered Ao nerve thresholds.141 Although the same laser both alone and in combination.157 more research is indicated, there seems to be some When the fluoride varnish and laser treatment were potential for use of the Nd:YAG laser as a method combined, more than 90% of tubule orifices were for obtaining temporary analgesia.142 occluded. When Nd:YAG lasers were compared to Er:YAG In a double-blind, controlled, split-mouth designed lasers for treatment of dentinal hypersensitivity, the clinical trial, the effect of a single Nd:YAG laser Nd:YAG laser was found to be more effective.161 application on dentinal sensitivity was assessed in 17 Aranha et al162 found that both neodymium and erbi­ patients, each of whom had two sensitive teeth. One um wavelengths could be effective in treating den­ tooth was treated with the laser and the other with a tinal sensitivity. A safety study evaluated the effects nonactivated laser probe (placebo). Although there of the Nd:YAG laser on oxygen saturation of pulpal were no statistically significant differences between blood in 65 patients with sensitive incisors and found

366 www.shayanNemodar.com Pu/pal Responses to Airborne Particle Abrasion little change before or after laser application.161 The Pulpal Responses to Er:YAG laser was found to be more effective for den­ tinal sensitivity treatment than a dentin desensitizer Airborne Particle Abrasion (Systemp Desensitizer, Vivadent).163 Both treatment modalities were successful, but after 2 months, dis­ comfort in the dentin desensitizer group increased Another technology, airborne particle abrasion to up to 65% of the baseline score. (kinetic cavity preparation), has recently been rein­ troduced for caries removal and cavity prepara­ Tooth bleaching tion.171 Airborne particle abrasion had fallen into Another dental application that has potential to disuse because the stream of particles used in tooth cause adverse pulpal reactions is the use of laser preparation procedures could not be controlled, irradiation of vital teeth in an attempt to change resulting in pitting and abrasion of adjacent teeth their color.164-167 Bleaching of endodontically treated and injury to gingival tissues.172 It was easily replaced teeth was once considered a normal part of post­ with high-speed, air-driven turbine handpieces, treatment endodontics. With the advent of resin which are more efficient and can construct a more composites and porcelain facings, which are used precisely defined tooth preparation.160 to improve the esthetics of vital teeth (especially Airborne particle abrasion technology has recent­ incisors), and because of the problems sometimes ly been refined and used as a method to produce associated with bleaching procedures (such as cervi­ "kinetic" cavity preparations.171 Its potential for pulpal cal resorption; see chapter 17), bleaching is seldom damage has not been fully investigated, but its use performed now. has been suggested for newer restorative materi­ Several investigations have examined the use of als and their direct placement in altered prepara­ lasers for this procedure. The effects of the presence tions, sometimes referred to as micropreparations. and absence of heat-enhancing colorant added to Advances in microabrasion technology allow for more bleaching gels was determined by comparing vari­ precise removal of enamel and dentin compared to ous heat-generating lamps to an argon laser.163Tem­ the older systems. peratures rose in response to all lights and the laser, Laurel! et al173 examined the pulpal responses to and the increased surface and intrapulpal tempera­ an air abrasion system in 120 molars and premolars tures could adversely impact patient sensitivity and of dogs. Two pressures (80 and 160 psi) and two health. Other studies have compared diode lasers aluminum oxide particle sizes (27 and 50 µm) were with LED irradiation. The use of bleaching gels with used. Class V cavity preparations were made and light-curing units and diode lasers has been com­ restored with an intermediate restorative material, pared with mixed results.165-167 Some believe that and the teeth were removed in 72 hours. Sections such tooth bleaching is the result of dehydration of were examined for odontoblast displacement, dis­ teeth and that much of the lightening effect is lost ruption of cell layers, inflammatory infiltrate, and on slow rehydration.16S--170 necrosis and were compared to preparations made with a high-speed turbine handpiece. The research­ Other procedures ers found that higher pressures and smaller particles While the use of lasers for hard tissue procedures caused significantly fewer pulpal effects than the is increasing, they have been approved for use in high-speed handpiece-treated teeth. This study soft tissue procedures, such as periodontal pocket represents the only controlled pulpal injury study elimination, closure of oral surgical wounds, frenec­ to date in the literature. While other articles in pro­ tomy, and operculum excisions, for approximately 10 prietary (commercial) journals report similar results, years. Their use for contouring of bone or removal of they are anecdotal. The ever-increasing popularity bone lesions is questionable at best, but they have of such technology indicates that more studies are been examined for root canal cleaning and shaping needed to be certain of the safety of these devices. procedures and for use in obturation. Further study Some air abrasion techniques advocate large must be carried out before their use can be fully particles and more pressure. This has been tested recommended. As their use in dentistry increases, on areas of tooth structure considered softer than there will be a continuing need to evaluate pulpal noncarious tooth structure.174 Alumina powders, responses following laser application to teeth. glass beads, crushed glass powders, and crushed

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powders of polycarbonate resin were applied to 17. Hatton JF, Holtzmann DJ, Ferrillo PJ Jr, Stewart GP. Effect of hand­ piece pressure and speed on intrapulpal temperature rise. Am J Dent intact human enamel and dentin and artificially 1994;7:108-110. demineralized dentin. The particle size of the abra­ 18. Hartnett JE, Smith WF. The production of heat in the dental pulp by use of 1961;63:210-214. sives and the air pressure on abraded depths were the air turbine. J Am Dent Assoc 19. Ottl P, Lauer HC. Temperature response of the pulp chamber during ultra also examined. Only crushed powders of polycar­ high-speed tooth preparation with diamond burs of different grit. J Pros­ bonate resin abraded the caries-model dentin with­ thet Dent 1998;80: 12-19. 20. Stanley HR. Traumatic capacity of high-speed and ultrasonic dental instru­ out reducing intact enamel and dentin. The results mentation. J Am Dent Assoc 1961;63:749-766. with the other materials were size and pressure 21. Stanley HR. Human Pulp Response to Restorative Dental Procedures. dependent, but the materials were generally consid­ Gainesville, FL: Starter, 1981. 22. Evans EA. New membrane concept applied to analysis of fluid shear- and ered to be difficult to control. micropipette-deformed red blood cells. Biophys J 1973;13:941-954. Direct pulp capping of pulp exposures made 23. Hung CT, Allen FD, Pollack SR, Brighton CT. Intracellular Cai+ stores and by air abrasion may force abrasive particles into extracellular Ca2+ are required for the real-time Cal+ response of bone cells experiencing fluid flow. J Biomech 1996;29: 1411-1417. the pulp, causing delayed healing.175 Clearly, more 24. Pashley DH. Dynamics of the pulpodentin complex. Crit Rev Oral Biol Med research is required before this technique can be 1996;7:104-133. 25. recommended without qualification. Goodis HE, Tao L, Pashley DH. Evaporative water loss from human dentine in vitro. Arch Oral Biol 1990;35:523-527. 26. 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White JM, Goodis HE. Laser interactions with dental hard tissues-Effects 164. Baik JW, Rueggeberg FA, Liewehr FR. Effect of light-enhanced bleach­ on the pulp/dentin complex. In: Shimano M, Maeda T, Suda H, Takahashi ing on in vitro surface and intrapulpal temperature rise. J Esthet Dent K (eds). Dentin/Pulp Complex. Tokyo: Quintessence, 1996:41-50. 2001;1 3:370-378. 145. Niemz M. Investigation and spectral analysis of the plasma-induced 165. Wetter NU, Barroso MC, Pelino JE. Dental bleaching efficacy with diode ablation mechanism of dental hydroxyapatite. Appl Phys B 1994;B58: laser and LED irradiation: An in vitro study. Lasers Surg Med 2004;35: 273-281. 254-258. 146. Sunakawa M, Tokita Y, Suda H. Pulsed Nd:YAG laser irradiation of the 166. Eldeniz AU, U:;umez A, U:;umez S, Oz!Urk A. Pulpal temperature rise tooth pulp in the cat. II. Effect of scanning lasing. Lasers Surg Med during light-activated bleaching. J Biomed Mater Res B Appl Biomater 2000;26:477-484. 2005;72:254-259. 147. Yamaguchi H, Kobayashi K, Sato Y, et al. Nd:YAG laser irradiation of the 167. Sulieman M, Rees JS, Addy M. Surface and pulp chamber temperature human dental pulp: Implications as a predictor of pulp hemodynamics. rises during tooth bleaching using a diode laser: A study in vitro. Br Dent J Lasers Surg Med 2000;26:270-276. 2006;200:631-634. 148. Murakani Y, Unno A, Kimura Y, et al. A histochemical study of the regen­ 168. Hein DK, Ploeger BJ, Hartup JK, Wagstaff RS, Palmer TM, Hansen LD. In­ eration process after injury by pulsed Nd:Y AG laser irradiation of root office vital tooth bleaching-What do lights add? Comp Cantin Educ Dent canals. Acta Histochem 2002;104:131-137. 2003;24:340-352. 149. Stabholz A, Neev J, Liaw LH, Stabholz A, Khayet A, Torabinejad M. Effect 169. Haywood VB. In-office bleaching: Lights, applications, and outcomes. Curr of ArF-193 nm excimer laser on human dentinal tubules. A scanning elec­ Prac 2009; 16:3-6. tron microscopic study. Oral Surg Oral Med Oral Pathol 1993;75:90-94. 170. Swift EJ Jr, May KN Jr, Wilder AD Jr, Heymann HO, Wilder RS, Bayne SC, 150. Pearson GJ, McDonald AV. Use of infrared and ultra-violet lasers in the Six-month clinical evaluation of a tooth whitening system using an innova­ removal of dental hard tissues. Lasers Med Sci 1994;9:227-237. tive experimental design. J Esthet Dent 1997;9:265-274. 151. McDonald A, Claffey N, Pearson G, Blau W, Setchell D. The effect of 171. Christiansen GJ. Cavity preparation: Cutting or abrasion. J Am Dent Assoc Nd:YAG pulse duration on dentine crater depth. J Dent 2001;29:43-53. 1996;127: 1651-1654. 152. Niemz MH. Cavity preparations with the Nd:YLF picosecond laser. J Dent 172. Morrison AH, Berham I. Evaluation of the airdent unit: Preliminary report. J Res 1995;74:1194-1199. Am Dent Assoc 1953;46:298. 153. Partovi F, Izatt JA, Cothren RM, et al. A model for thermal ablation of 173. Laurell KA, Carpenter W, Daughtery D, Beck M. Histopathologic effects of biological tissue using laser radiation. Lasers Surg Med 1987;7: 141-154. kinetic cavity preparation for the removal of enamel and dentin. Oral Surg 154. McCormack SM, Fried D, Featherstone JD, Glena RE, Seka W. Scanning Oral Med Oral Pathol Oral Radial Endod 1995;80:214-225. electron microscope observations of C02 laser effects on dental enamel. J 174. Horiguchi S, Yamada T, lnokoshi S, Tagami J. Selective caries removal with Dent Res 1995;74: 1702-1708. air abrasion. Oper Dent 1998;23:236-243. 155. McKenzie AL. Physics of thermal processes in laser-tissue interaction. Phys 175. Cardenas-Duque LM, Yoshida M, Goto G. Pulpal response to different pulp Med Biol 1990;35: 1175-1209. capping methods after pulp exposure by air abrasion. J Clin Pediatr Dent 2002;26:269-273.

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llan Rotstein, DDS James H. Simon, DDS

Endodontic-periodontal diseases often present chal­ ment (Fig 16-1). Exposure of dentinal tubules may lenges to the clinician in their diagnosis, treatment, result from developmental defects, disease, or peri­ and prognosis assessment. Etiologic factors such odontal or surgical procedures. Radicular dentinal as microorganisms as well as contributing factors tubules extend from the pulp to the cementoden­ such as trauma, root resorptions, perforations, and tinal junction. They run a relatively straight course dental malformations play a role in the development and range in size from 1 to 3 µm in diameter.1 The and progression of such diseases. The treatment and diameter of the tubules decreases with age or as prognosis of endodontic-periodontal diseases vary a response to chronic low-grade stimuli that cause and depend on the etiology, pathogenesis, and cor­ apposition of highly mineralized peritubular dentin. rect recognition of each specific condition. There­ The number of dentinal tubules varies from approxi­ fore, understanding the interrelationship between mately 8,000/mm2 at the cementodentinal junction endodontic and periodontal diseases will enhance to 57,000/mm2 at the pulpal end. In the cervical area the clinician's ability to establish a correct diagnosis, of the root, the number of dentinal tubules is about select a treatment plan based on biologic and clini­ 15,000/mm2. cal evidence, and assess the prognosis of the teeth When the cementum and enamel do not meet at involved. the cementoenamel junction, these tubules remain exposed, thus creating pathways of communication between the pulp and the periodontal ligament. Depending on their location, these pathways can I Anatomical Relationships contribute to conditions such as cervical dentinal hypersensitivity. Fluid and irritants may flow through patent dentinal tubules, and, in the absence of an The dental pulp and the periodontium are con­ intact enamel or cementum covering, the pulp may nected via three main avenues of communication: (7) be considered exposed to the oral environment via exposed dentinal tubules, (2) smaller portals of exit, the gingival sulcus or periodontal pocket. Experi­ and (3) the apical foramen. mental studies have demonstrated that application of soluble material from bacterial plaque to exposed dentin could cause pulpal inflammation, indicat­ Exposed dentinal tubules ing that dentinal tubules may provide ready access between the periodontium and the pulp.2 Additional Exposed dentinal tubules in areas devoid of cemen­ details on the parameters affecting diffusion of sub­ tum may serve as viable communication pathways stances through the dentinal tubules can be found in between the dental pulp and the periodontal liga- chapter 3.

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Fig 16-1 (a) Scanning electron micrograph of open dentinal tubules (original magnification x 500). (b) Higher magnification demonstrates the absence of the odontoblastic process (original magnification x 2,000).

Fig 16-2 Nonsurgical endodontic treatment of a max­ illary central incisor with a lateral radiolucency. (a) Pre­ operative radiograph showing previously treated canal with a mesiolateral lesion. (b) Tooth after retreatment and the restoration of the root canal with thermoplas­ ticized gutta-percha. Note the lateral canal extending toward the lesion. (c) One-year recall radiograph reveal­ ing evidence of active healing.

Scanning electron microscopic studies have dem­ tion of impression materials, microradiography, light onstrated that dentinal exposure at the cemen­ microscopy, and scanning electron microscopy.9-15 toenamel junction occurs in about 18% of teeth It is estimated that 30% to 40% of all teeth have in general and in 25% of anterior teeth in particu­ such ancillary canal systems, and the majority of lar.3 In addition, the same tooth may have different them are found in the apical third of the root. De cementoenamel junction characteristics, present­ Deus12 reported that 17% of teeth presented mul­ ing dentinal exposure on one surface while the tiple canal systems in the apical third of the root, other surfaces are covered with cementum.4 This area about 9% in the middle third, and less than 2% in becomes important in assessing the progression of the coronal third. However, it seems that the incidence endodontic pathogens as well as the effect of root of periodontal disease associated with these types scaling and planing on cementum integrity, trauma, of canals is relatively low. Kirkham, 13 studying 1,000 and bleaching-induced pathosis.S-7 Other areas of human teeth with extensive periodontal disease, dentinal communication may be through develop­ found that only 2% of such canals were associated mental grooves, both palatogingivally and apically.8 with the involved periodontal pocket. Other canal systems in the furcation of molars may also be a direct pathway of communication between Other portals of exit the pulp and the periodontium.10·14 The incidence of accessory canals may vary from 23% to 76%.11·12·16 Lateral and accessory canals can be present any­ These accessory canals contain connective tissue and where along the length of the root (Fig 16-2). Their blood vessels that connect the circulatory system of incidence and location have been well documented the pulp with that of the periodontium. However, not in both animal and human teeth using a variety of all of these canals extend the full length from the pulp methods. Such methods include dye perfusion, injec- chamber to the floor of the furcation.16

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apical foramen and/or adjacent to openings of the smaller canal systems.18 Inflammatory by-products of pulpal origin may permeate the apex, smaller canals in the apical third of the root canal system, and exposed dentinal tubules and trigger an inflamma­ tory vascular response in the periodontium. Among those are living pathogens such as certain bacterial strains (including spirochetes), fungi, and viruses,19-28 as well as other noxious substances.28-32 Many of these are similar to pathogens encountered in peri­ odontal inflammatory disease. In certain cases, pulp­ al disease will stimulate epithelial growth that affects Fig 16-3 Micrograph of a maxillary lateral incisor with a necrotic pulp associ­ ated with a lateral inflammatory process in the periodontal ligament. (a) Main the integrity of the periradicular tissues.33·34 canal, accessory canal, and the resultant inflammatory response in the periodon­ The effect of periodontal inflammation on the pulp tal ligament are evident (Masson trichrome stain; original magnification x 100). is controversial, and conflicting studies abound.17•35-42 (b) Higher magnification of the area shows chronic inflammation with proliferat­ ing epithelium (Masson trichrome stain; original magnification x 200). It has been suggested that periodontal disease has no effect on the pulp at least until it involves the apex.37 On the other hand, results of several studies Seltzer et al17 reported that pulpal inflammation have suggested that the effect of periodontal disease may cause an inflammatory reaction in the interra­ on the pulp is degenerative, including an increase in dicular periodontal tissues. The presence of these calcifications, fibrosis, and collagen resorption as well patent smaller canals is a potential pathway for as a direct inflammatory effect.43·44 It appears that the the spread of microorganisms and their toxic by­ pulp is usually not severely affected by periodontal products from the pulp to the periodontal ligament disease until recession has opened an accessory canal and vice versa, resulting in an inflammatory process to the oral environment. At this stage, pathogens in the involved tissues (Fig 16-3). leaking from the oral cavity through the accessory canal into the pulp may cause a chronic inflamma­ tory reaction followed by pulpal necrosis. However, as Apical foramen long as the accessory canals are protected by sound cementum, necrosis usually does not occur. Addi­ The apical foramen is the principal route of commu­ tionally, if the microvasculature of the apical foramen nication between the pulp and periodontium. Micro­ remains intact, the pulp will maintain its vitality.43 bial and inflammatory by-products may exit readily The effect of periodontal treatment on the pulp through the apical foramen to cause periradicular is similar during scaling, curettage, or periodon­ pathosis. The apex is also a potential portal of entry tal surgery if accessory canals are severed and/or of inflammatory by-products from deep periodontal opened to the oral environment. In such cases, pockets to the pulp. Pulpal inflammation or pulpal pathogenic invasion and secondary inflammation necrosis extends to the periradicular tissues, causing and necrosis of the pulp can occur. a local inflammatory response often associated with bone and root resorptions.17 Endodontic treatment aims to eliminate the intraradicular etiologic factors, Etiology thereby leading to healing of the affected perira­ dicular tissues. Live pathogens and infectious biofilms Among the live pathogens encountered in a diseased pulp and periradicular tissues are bacteria, fungi, and viruses (Figs 16-4 to 16-6). These pathogens and their I Disease Relationships by-products may affect the periodontium in a variety of ways and must be eliminated during root canal treatment. When the pulp becomes inflamed, it elicits an inflam­ matory response in the periodontal ligament at the

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Fig 16-4 Periapical Actinomyces infection. This case demonstrates the growth of bacteria past the apical foramen and its invasion of apical cementum and periapi­ cal tissues. (a) Radiograph of a maxillary central incisor with a necrotic pulp showing a large periapical lesion. (b) Radiograph after nonsurgical endodontic therapy. Symptoms persisted after treatment, so apical surgery was performed subsequently. (c) Photomicrograph showing part of the root with the attached lesion (hematoxylin­ eosin [H&E] stain; original magnification x 20). (d) Colonies of Actinomyces in the lumen of the lesion (H&E stain; original magnification x 100). (e) A large colony of Actinomyces (H&E stain; original magnification x 100). (f) Foamy macrophages attacking the bacteria (H&E stain; original magnification X400). (g) Edge of the bacterial megacolony, revealing the absence of inflammatory cells, which are unable to penetrate the colony (H&E stain; original magnification x 200). (h) Detail of the bacterial colony (H&E stain; original magnification x 200). (i) Center of the colony, devoid of inflammatory cells (H&E stain; original magnification x 200). OJ Viable bacteria within the apical cementum (H&E stain; original magnification X40).

Fig 16-5 Fungi in a persistent periapical lesion. (a) Radiograph of a maxillary lateral incisor with a necrotic pulp and a periapical radiolucency. (b) Radiograph taken immediately after nonsurgical treatment. (c) Radiograph taken at the 3-month recall. The patient is still symptomatic, and the periapical radiolucency is larger. (d) Transmission electron micrograph revealing the growing hyphae of a fungus (original magnification X2,000). (e) Higher magnifica­ tion of the hyphae, showing the cell wall (original magnification X4,000). (f) Reproductive fungal spores (original magnification X4,000).

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Fig 16-6 Transmission elec­ finding indicative of the association between infect­ tron micrograph of the nucleus ed pulp tissue and periodontal pathoses. of a macrophage in a periapical lesion, suggesting a possible viral Jansson et al54 assessed the effect of endodontic infection (original magnification pathogens on marginal periodontal wound healing XS,000). of denuded dentin surfaces surrounded by healthy periodontal ligament. Their results showed that, in infected teeth, the defects were covered by 20% more epithelium, while the uninfected teeth showed only 10% more connective tissue coverage. The authors concluded that pathogens in necrotic root canals may stimulate epithelial downgrowth along denuded dentin surfaces with marginal communica­ tion and thus augment periodontal disease. Jansson et al,55 in a retrospective 3-year study, evaluated radiographs of 175 endodontically treated single-rooted teeth from 133 patients. Patients who Bacteria were more prone to periodontitis and exhibited Bacteria play a crucial role in the formation and evidence of endodontic treatment failures showed progression of both endodontic and periodontal approximately three times greater marginal bone diseases.26·45-52 The periradicular tissues become loss than did patients without endodontic infection. involved when bacteria invade the pulp, causing Additionally, the effect of endodontic infection on either partial or total necrosis. In a classic study, periodontal probing depth and the presence of fur­ Kakehashi et al45 demonstrated the relationship cation involvement in mandibular molars was inves­ between the presence of bacteria in the pulp and tigated.56 Endodontic infection in mandibular molars periradicular diseases. In this study, pulps of normal was associated with more attachment loss in the fur­ rats were exposed and left open to the oral envi­ cal area. It was therefore suggested that endodontic ronment. Consequently, pulpal necrosis ensued, infection in molars associated with periodontal dis­ followed by periradicular inflammation and lesion ease might enhance the progression of periodontitis formation. However, when the same procedure was by spreading pathogens through accessory canals performed on germ-free rats, not only did the pulps and dentinal tubules.56 However, when the endodon­ remain vital and relatively uninflamed but the expo­ tic infection was treated successfully, the furcal lesion sure sites showed evidence of dentin repair. healed, indicating that there was only one infective Moller et al46 confirmed these findings in monkeys vector present. and reported that uninfected necrotic pulp tissue Proteolytic bacteria predominate in the root did not induce periradicular lesions or inflamma­ canal flora, which changes over time to a more tory reactions. Nonetheless, once the pulp became anaerobic microbiota.57·58 Rupf et al59 studied the infected, periradicular lesions and inflammation in profiles of periodontal pathogens in pulpal and peri­ the apical tissues occurred. Korzen et al47 reported odontal diseases associated with the same tooth. similar results and suggested that pulpal infections Specific polymerase chain reaction methods were were usually mixed infections. Collectively, these used to detect Actinobacillus actinomycetemcomi­ studies provided early key evidence regarding the tans, Bacteroides forsythus, Eikenella corrodens, role of microorganisms in pulpal and periradicular Fusobacterium nucleatum, Porphyromonas gingiva­ diseases. lis, Prevotella intermedia, and Treponema denticola. Blomlof et al53 created defects on the root sur­ These pathogens were found in all endodontic sam­ faces of intentionally extracted monkey teeth with ples, and the same pathogens were found in teeth either open or mature apices. The canals were with chronic apical periodontitis and chronic adult either infected or filled with calcium hydroxide and periodontitis. Therefore, it appears that periodontal reimplanted back in their sockets. After 20 weeks, pathogens accompany endodontic infections and marginal epithelial downgrowth was found on the that endodontic-periodontal interrelationships are a denuded dentin surfaces of the infected teeth, a critical pathway for both diseases.

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Spirochetes are another class of microorganism original pathogenic bacterial form and may then be associated with both endodontic and periodontal responsible for acute exacerbation of chronic perira­ diseases. Spirochetes are usually found more fre­ dicular lesions.71 quently in subgingival plaque than in root canals. Several studies have shown a large diversity of Fungi (yeasts) oral treponemes present in subgingival biofilms The presence and prevalence of fungi associat­ of periodontal pockets.60-62 It has been previous­ ed with endodontic disease are well document­ ly proposed that the presence or absence of oral ed.27 Yeast colonization associated with radicular spirochetes can be used to differentiate between pathosis has been demonstrated in untreated root endodontic and periodontal abscesses.2° Currently, caries,73.74 dentinal tubules,75-77 failing root canal however, the presence of spirochetes in the root treatments,78-81 apices of teeth with asymptomatic canal system is well documented and has been apical periodontitis,82 and periradicular tissues.83 demonstrated by different identification techniques, Most studies have reported that the prevalence of including darkfield microscopy, electron microscopy, fungi in cultured root canal systems varies and may and biochemical identification.23·24·63--07 reach up to 26% in untreated root canals73·84-87 and The differences in the reported incidences of spi­ 33% in previously treated canals.73.79.3o.33.33 A few rochetes associated with endodontic infection may studies, however, have demonstrated an even higher be attributed to the different detection methods incidence of up to 55%.77·89 used. It has been demonstrated that the spirochete The predominant fungi recovered were Candida species most frequently found in root canals are T a/bicans.88·90 C albicans has been detected in 21 % of dentico/a65·67 and Treponema maltophilum.66 The infected root canals using 18S rRNA-directed species­ main virulence factor of T denticola includes surface­ specific primers87 and also has shown an ability to expressed proteins with cytotoxic activities, such colonize canal walls and invade dentinal tubules.77 as the major surface protein and the chymotrypsin­ Other species of fungi, such as Candida glabrata, like protease complex, extracellular or membrane­ Candida guilliermondii, Candida incospicua,88 and associated proteolytic and hydrolytic enzymes, and Rhodotorula mucilaginosa,25 were also detected. metabolites.68 This microorganism possesses an Factors affecting the colonization of the root array of virulence factors associated with periodontal canal by fungi are not completely understood. It disease and may also participate in the pathogen­ appears, however, that among the predisposing esis of periradicular disease.67 factors of this process are immunocompromising The virulence factors of T maltophilum have not diseases such as cancer,76 certain intracanal medi­ yet been fully elucidated. It has been proposed that caments,73 local and systemic antibiotics,74·91 and · the motility of T maltophilum, caused by the rota­ previous unsuccessful endodontic therapy.80·92 93 tion of its periplasmic flagella, might contribute to Reduction of specific strains of bacteria in the root its pathogenicity.69 This microorganism was also fre­ canal during endodontic treatment may allow fungi quently isolated from patients with rapidly progres­ overgrowth in the remaining low-nutrient environ­ sive periodontitis.70 However, the exact role of this ment.80·93 Another possibility is that fungi may gain microorganism in combined endodontic-periodontal access to the root canal from the oral cavity as a diseases requires further investigation. result of poor asepsis during endodontic treatment L-form bacteria (ie, bacteria without cell walls) or post-preparation procedures. It has been report­ also have been suggested to have a role in perira­ ed that approximately 20% of patients with adult dicular disease.71 Some bacterial strains can undergo periodontitis also harbor subgingival fungi,94·95 and morphologic transition to their L-form after expo­ C albicans was the most common species isolated.96 sure to certain agents, particularly penicillin.72 The In addition, it has been demonstrated that the pres­ L-form and the bacterium may appear individually ence of fungi in root canals is directly associated or together and may transform from one variant to with their presence in saliva.25 These findings further another with numerous intermediate L-form transi­ confirm the importance of using aseptic endodontic tional stages. This may occur either spontaneously and periodontal techniques, maintaining the integ­ or by induction in a cyclic manner. Under certain rity of dental hard tissues, and covering the tooth conditions, depending on host resistance factors crown as soon as practical with a well-sealed perma­ and bacterial virulence, the L-forms revert to their nent restoration to prevent reinfection.

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Viruses Infectious biofilms There is increasing evidence to suggest that virus­ The majority of bacteria in virtually all natural eco­ es may be associated with both endodontic and systems grow in biofilms, and their growth in affected periodontal diseases. Herpes simplex virus was fre­ tissues is characterized by matrix-enclosed commu­ quently detected in gingival crevicular fluid and gin­ nities.108·109 Biofilm microcolonies are composed of gival biopsies of periodontal lesions from patients approximately 15% cells (by volume) embedded in with periodontal disease.97·98 Human cytomegalovirus 85% matrix material.110 They are bisected by ramifying was observed in about 65% of periodontal pocket water channels that carry bulk fluid into the commu­ samples and about 85% of gingival tissue samples.97 nity by convective flow.111 The structural composition Epstein-Barr virus type I was observed in more than of biofilms indicates that these communities are regu­ 40% of periodontal pocket samples and in about lated by signals analogous to the hormones and 80% of gingival tissue samples.97 Gingival herpes­ pheromones that regulate many cellular eukaryotic viruses were found to be associated with increased communities.110 occurrence of subgingival P gingivalis, B forsythus, P Biofilm formation has a developmental sequence intermedia, Prevotella nigrescens, T denticola, and A that results in the formation of a mature commu­ actinomycetemcomitans, thus suggesting their role in nity of tower-shaped and mushroom-shaped micro­ the overgrowth of periodontal pathogenic bacteria.99 colon ies, with some variation between species. The presence of viruses in the dental pulp was The sequence of events usually is microbial surface first reported in a patient with AIDS.100 The DNA attachment, cell proliferation, matrix production, of human immunodeficiency virus (HIV) was also and detachment.112 Biofilm formation and detach­ detected in periradicular lesions.101 However, it has ment are under the control of chemical signals that not been established that HIV can directly cause regulate and guide the formation of slime-enclosed pulpal disease. Herpes simplex virus was also stud­ microcolonies and water channels.110 It has been ied in relation to endodontic disease. It seems that, stated that microbial biofilms constitute the most unlike its role in periodontal disease, herpes simplex "defensive" life strategy that can be adopted by virus does not play a significant role in endodontic prokaryotic cells.113 In very hostile environments, such disease.102,103 as extreme heat, acidity, or dryness, this stationary On the other hand, other common types of human mode of growth is inherently defensive because bac­ viruses may be involved in pulpal and periradicular dis­ terial cells are not swept into areas where they can be eases. It has been suggested that human cytomegalo­ killed.110 virus and Epstein-Barr virus play a role in the pathogen­ Infectious biofilms are difficult to detect through esis of symptomatic periradicular lesions.104·105 It seems routine diagnostic methods and confer great resis­ that active infection may give rise to production of an tance to host defenses and antibiotic therapies.112 array of cytokines and chemokines with the potential In addition, biofilms facilitate the spread of anti­ to induce immunosuppression or tissue destruction.106 biotic resistance by promoting horizontal gene Herpesvirus activation in periradicular inflammatory transfer. They are also actively adapted to environ­ cells may impair the host defense mechanisms and mental stresses, such as alteration in nutritional qual­ give rise to overgrowth of bacteria, as seen in peri­ ity, cell density, temperature, pH, and osmolarity.114 odontal lesions. Herpesvirus-mediated immune sup­ Prolonged starvation induces loss of cultivability pression may be detrimental in periradicular infections under standard conditions while the microorganism because host responses in the granulomatous tissue remains metabolically active and structurally intact.115 are already compromised.107 Alterations between pro­ This is considered the main reason for the low detec­ longed periods of herpesvirus latency interrupted by tion rate of biofilm infections by routine culture periods of activation may explain some burstlike symp­ methods. To date, however, the exact role of bio­ tomatic episodes of periradicular disease. Frequent films in the interrelationship between endodontic reactivation of periradicular herpesvirus may support and periodontal diseases has not been fully eluci­ rapid periradicular breakdown. The absence of herpes­ dated. virus infection or viral reactivation may be the reason that some periradicular lesions remain clinically stable for extended periods of time.104

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Fig 16-7 Foreign body particles in a periapical lesion. (a) Radiograph of a symptomatic maxillary central incisor with a large periapical lesion. En­ dodontic treatment had been performed 27 years previously. (b) Photomicrograph of apical tissue, showing foreign body particles in the presence of giant cells (H&E stain; original magnification X40). (c) Higher magnification of the foreign body particles and giant cells (H&E stain; original magnification x 200). (d) Part of the foreign body. When put under polarized light, the substance responds as vegetable matter (H&E stain; original magnification X400). The diagnosis is that part of a paper point had extended past the apical fora men.

Nonliving pathogens rial in a chronic inflammatory infiltrate. Mechanical or Nonliving pathogens can be either extrinsic or intrin- surgical removal of the foreign bodies is usually the sic, depending on their origin and nature. treatment of choice.

Extrinsic (foreign bodies) Intrinsic Foreign bodies are often found in association with Epithelium. Among the normal components of the the inflammatory process of the periradicular tis­ lateral and apical periodontal ligament are the epi­ sues (Figs 16-7 and 16-8). Although endodontic and thelial rests of Malassez. The term rests is misleading periodontal diseases are primarily associated with in that it evokes a vision of discrete islands of epithe­ the presence of microorganisms, the presence of lial cells. These rests are actually a fishnet-like, three­ certain foreign substances in situ may explain some dimensional, interconnected network of epithelial treatment failures. Substances such as dentin and cells. In many periradicular lesions, epithelium is not cementum chips,11&-118 amalgam,118·119 root canal fill­ present and therefore is presumed to have been ing materials,11 6•11a-120 cellulose fibers from absorbent destroyed.126 If the rests remain, they may respond paper points,119•121•122 gingival retraction cords,123 to stimuli by proliferating in an attempt to wall off leguminous foods,124 and calculus-like deposits125 the irritants coming through the apical foramen. Epi­ have all been reported to trigger periradicular thelium can be surrounded by chronic inflammatory inflammatory reactions. tissue. This type of lesion is termed an epitheliated A foreign body response may occur to any of granuloma, and, if not treated, the epithelium will these substances; clinically, such conditions may be continue to proliferate in an attempt to wall off the either symptomatic or asymptomatic. Microscopical­ source of irritation communicating from the apical ly, these lesions demonstrate the presence of multi­ foramen. nucleated giant cells surrounding the foreign mate-

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Fig 16-8 Multiple etiologic factors past the apical foramen associated with failing treatment. (a) Radiograph showing treatment failure in a maxillary second premolar. The tooth had been treated by intentional reimplantation, during which the apical lesion was removed. (b) Photomicrograph of the lesion, revealing presence of foreign material (H&E stain; original magnification x 20). (c) Higher magnification showing unidentified purple foreign material and necrotic muscle tissue (H&E stain; original magnification x 100). (d) Different area of the lesion, showing necrotic muscle with viable bacterial colonies (H&E stain; original magnification x 100). (e) Necrotic muscle tissue infected by bacteria and the presence of lentil beans (pulse granuloma) (H&E stain; original magnification x 100). m One-year follow-up radiograph. The tooth is asymptomatic and nonmobile, and bony healing is evident.

Fig 16-10 (right) Photomicrograph of a true inflammatory cyst. It is a three­ dimensional epithelial-lined lesion with no connection to the root canal system and apical foramen (Masson trichrome stain; original magnification x 20).

Fig 16-9 (far right) Photomicrograph of a bay cyst associated with a root canal that opens directly into the lumen of the lesion (H&E stain; original magnification x 20).

The term bay cyst has been introduced for the There has been some confusion regarding the microscopic representation of this situation.34 This is diagnosis when lesions are studied only on curetted a chronic inflammatory lesion in which an epithelial biopsy material. Because the tooth is not attached lining surrounds the lumen but the lumen has a direct to the lesion, the orientation to the apex is lost. communication with the root canal system through Therefore, the criterion used for diagnosis of a cyst the apical foramen (Fig 16-9). On the other hand, a is a strip of epithelium that appears to be lining a true cyst is the completion of the epithelial prolifera­ cavity. Thus, curettage of a bay cyst and a true cyst tive lesion. It is a three-dimensional, epithelium-lined could lead to the same microscopic diagnosis. A cavity with no communication between the lumen and bay cyst could be sectioned in such a way that it the canal system (Fig 16-10). When periapical lesions could resemble or give the appearance of a true are studied in relation to the root canal, a clear distinc­ cyst. This distinction between a bay cyst and a true tion should be made between these two entities.33-34 cyst is important from the standpoint of healing.

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Fig 16-11 Cholesterol clefts in a periapical lesion. (a) Photomicrograph of a cyst with a thick fibrous wall. Embedded in the wall is a large col­ lection of cholesterol clefts (Masson trichrome stain; original magnification x 20). (b) Higher magnification showing empty clefts where cho­ lesterol has been dissolved during the histologic preparation (Masson trichrome stain; original mag­ nification x 100).

Fig 16-12 (a) Photomicrograph of a periapical lesion showing the presence of Russell bodies (H&E stain; original magnification x 200). (b) Transmission electron micrograph demonstrating the round, amorphous shape of these structures (H&E stain; original magnification xSOO).

Tr ue cysts must be surgically removed, but bay cysts plasma cells, and macrophages that die in great that communicated with the root canal may heal numbers and disintegrate in chronic periradicular with nonsurgical root canal treatment. Because root lesions131; or by the circulating plasma lipids.128 It canal treatment can directly affect the lumen of the is possible, however, that all of these factors may bay cyst, the environmental change may bring about contribute to the accumulation, concentration, and resolution of the lesion. The true cyst is independent crystallization of cholesterol in a periradicular lesion of the root canal system, so conventional root canal (Fig 16-11). treatment may not have an effect on this entity. It has been suggested that accumulation of cho­ The formation of a cyst and its progression from a lesterol crystals in inflamed periradicular tissues in bay cyst to a true cyst occurs over time. Valderhaug, 127 some cases might cause failure of endodontic treat­ in a study performed in monkeys, found no cyst for­ ment.30·132 The macrophages and the multinucleated mation until at least 6 months after the canal contents giant cells that congregate around cholesterol crystals became necrotic. Thus, the longer a lesion was pres­ are not efficient enough to destroy the crystals com­ ent, the greater the probability that it would become pletely. In addition, the accumulation of macrophages a true cyst. However, the incidence of true cysts is and giant cells around the cholesterol clefts in the probably less than 10%.34 This may explain the rela­ absence of other inflammatory cells, such as neutro­ tively high success rate of nonsurgical root canal treat­ phils, lymphocytes, and plasma cells, suggests that ment in teeth associated with periradicular lesions. the cholesterol crystals induce a typical foreign body reaction.30 Cholesterol_ The presence of cholesterol crystals in apical periodontitis is a common histopathologic Russell bodies. Russell bodies can be found in most finding.128-132 With time, the cholesterol crystals are inflamed tissues throughout the body, including the dissolved and washed away, leaving behind spac­ periradicular tissues (Fig 16-12). These are small, es as clefts. The reported incidence of cholesterol spherical accumulations of an eosinophilic substance clefts in periradicular disease varies from 18% to found within or near plasma cells and other lym­ 44%.128·130.131 It has been suggested that the crystals phoid cells. The presence and occurrence of Russell could be formed from cholesterol released by dis­ bodies in oral tissues and periradicular lesions is well integrating erythrocytes of stagnant blood vessels documented.133·134 within the periradicular lesion130; by lymphocytes,

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Fig 16-13 (a) Photomicrograph showing Rushton hyaline bodies in the epithelial lining of a periapical cyst (H&E stain; original magnification x 20). (band c) Higher­ magnification photomicrographs demonstrating the pleomorphism of these bodies (H&E stain; original magnification x 100).

Studies have indicated the presence of Russell Charcot-Leyden crystals_ Charcot-Leyden crystals bodies in about 80% of periradicular lesions. Recent­ are naturally occurring hexagonal bipyramidal crys­ ly, large intracellular and extracellular Russell bodies tals derived from the intracellular granules of eosino­ were also found in inflammatory pulp tissue of carious phils and basophils.140-142 Their presence is most primary teeth.31 It is hypothesized that Russell bod­ often associated with increased numbers of periph­ ies are caused by synthesis of excessive amounts eral blood or tissue eosinophils in parasitic, allergic, of normal secretory protein in certain plasma cells neoplastic, and inflammatory diseases.140·141·143 Acti­ engaged in active synthesis of immunoglobulins. vated macrophages are reported to have an impor­ The endoplasmic reticulum becomes greatly dis­ tant role in the formation of Charcot-Leyden crystals tended, thus producing large homogenous eosino­ in several disease processes.144 Charcot-Leyden crys­ philic inclusions.135 However, the incidence of Russell tals and damaged eosinophils, along with their gran­ bodies, their production mechanism, and their exact ules, have been observed within macrophages.143-145 role in pulpal inflammation has not yet been fully It has been proposed that, after the degranula­ elucidated. tion of eosinophils, Charcot-Leyden crystal protein could be phagocytized into acidified membrane­ Rushton hyaline bodies_ The presence of Rushton bound lysosomes.143 At some point, Charcot-Leyden hyaline bodies is a feature unique to some odon­ crystal protein would begin to crystallize, forming togenic cysts. Their frequency varies from 2.6% to discrete particles that increase in volume and den­ 9.5%.136 Rushton hyaline bodies usually appear within sity over time. Ultimately, these crystals would be the epithelial lining or the cyst lumen (Fig 16-13). They released via phagosomal exocytosis or by piercing have a variety of morphologic forms, including linear through the membrane of the phagosome and mac­ (straight or curved), irregular, rounded, and polycyclic rophage cytoplasm, becoming free in the stromal structures, or they may appear granular.29•136 tissue. The exact nature of Rushton hyaline bodies is not Recent findings support the theory that acti­ fully understood. It has been suggested that they are vated macrophages have a role in the formation keratinous,128 of hematogenous origin,137 a special­ of Charcot-Leyden crystals.32 In addition, the pres­ ized secretory product of odontogenic epithelium,138 ence of Charcot-Leyden crystals can be detected or degenerated red blood cells.29 Some authors within a periradicular lesion that failed to resolve have suggested that Rushton hyaline bodies are after conventional endodontic treatment (Fig 16-14). material left behind at the time of a previous surgical Although the biologic and pathologic roles of operation.139 It is not clear yet why the Rushton hya­ Charcot-Leyden crystals in endodontic and peri­ line bodies form mostly within the epithelium. odontal disease are still unknown, some cases of treatment failure may be attributed to them.

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Fig 16-14 Charcot-Leyden crystals in a periapical lesion. (a) Maxillary lateral inci­ sor with necrotic pulp and a periapical lesion. (b) Radiograph taken 9 months after endodontic treatment. The tooth is still symptomatic, and the lesion is larger. (c) Pho­ tomicrograph of the lesion reveals only acute and chronic inflammatory infiltrate (H&E stain; original magnification X40). (d to f) May-GrUnwald-Giemsa staining reveals the presence of Charcot-Leyden crystals (original magnification x 100). (g and h) Polarized light demonstrates refraction of the Charcot-Leyden crystals (original magnification x 200 and X400, respectively).

f

Contributing factors nosed and corrected.150 In recent years, retreatment techniques have improved dramatically because of Poor endodontic treatment the use of the operating microscope and develop­ Correct endodontic procedures and techniques are ment of a new armamentarium. key factors for treatment success. Assessments of the retention rate of endodontically treated teeth Poor restoration have found that nonsurgical endodontic treatment Coronal leakage is an important cause of endodontic is a predictable procedure with excellent long-term treatment failure. Root canals may become recon­ prognosis.14&-148 It is imperative that the canal sys­ taminated by microorganisms if there is a delay in tem be completely cleaned and shaped and well placement of a coronal restoration or fracture of obturated to enhance successful outcomes. Poor the coronal restoration and/or the tooth.151 Madison endodontic treatment allows reinfection of the canal, and Wilcox152 found that exposure of root canals to which may often lead to treatment failure.149 the oral environment allowed coronal leakage to Endodontic failures can be treated either by occur, in some cases along the entire length of the orthograde or retrograde retreatment with good root canal. Ray and Trope153 reported that teeth with success rates. The success rate for retreatment is defective restorations and adequate root canal fill­ similar to that of initial conventional endodontic ings had a higher incidence of failure than did teeth treatment if the cause of failure is properly diag- with inadequate root canal fillings and adequate res-

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torations. Te eth in which both the root canal fillings classified as enamel fracture, crown fracture with­ and restorations were adequate had only 9% failure, out pulpal involvement, crown fracture with pulpal whereas teeth in which both root canal fillings and involvement, crown-root fracture, root fracture, luxa­ restorations were defective had a failure rate of about tion, and avulsion.160 Treatment of traumatic dental 82%.153 injuries varies depending on the type of injury, and it Saunders and Saunders154 showed that coronal will determine pulpal and periodontal ligament heal­ leakage was a significant clinical problem in endo­ ing prognosis.161 dontically treated molars. In an in vitro study, they found that packing excess gutta-percha and sealer Enamel fracture over the floor of the pulp chamber after completion This type of injury involves the enamel only and of root canal filling did not provide a better seal of includes enamel chipping and incomplete fractures the root canals. It is therefore recommended that or enamel cracks. Treatment usually includes grind­ excess gutta-percha restorative material be removed ing and smoothing of the rough edges or restora­ to the level of the canal orifices and that the floor of tion of the missing enamel structure. When only the pulp chamber be protected with a well-sealed the enamel is involved, the pulp usually maintains restorative material.154 its vitality and the prognosis for both pulp and peri­ Coronal restoration is the primary barrier against odontium is good. coronal leakage and bacterial contamination of the root canal. Therefore, lack of coronal coverage fol­ Crown fracture without pulpal involvement lowing endodontic treatment can significantly com­ This is an uncomplicated fracture that involves enam­ promise the prognosis of the tooth.147 For this rea­ el and dentin without pulpal exposure. Treatment son, it is essential that the root canal system be may include conservative restoration with resin com­ protected by good endodontic obturation and a posite or reattachment of the separated fragments. well-sealed coronal restoration. Nevertheless, even It has been reported that reattachment of dentin­ popular permanent restorative materials may not enamel crown fragments is a conservative possibility always prevent coronal leakage.155 Cemented com­ for crown restoration.162 The pulpal and periodontal plete crowns156·157 as well as dentin-bonded crowns158 prognosis is good. have also shown leakage. A review of the literature159 examined the fac­ Crown fracture with pulpal involvement tors associated with the long-term prognosis of This is a complicated fracture involving enamel and enodontically treated teeth. These results indicat­ dentin and exposure of the pulp. The extent of the ed that (1) post space preparation and cementa­ fracture helps to determine the necessary pulpal tion should be performed with rubber dam isola­ and restorative treatments.160 A small fracture may tion; (2) the post space should be prepared with indicate the need for vital pulp therapy followed by a heated plugger; (3) a minimum of 3 mm of root placement of an acid-etched resin composite resto­ canal filling should remain in the preparation; (4) ration. A more extensive fracture may require partial the post space should be irrigated and dressed as pulpectomy or complete root canal treatment. during root canal treatment; (5) leak-proof restora­ The stage of tooth maturation is an important tions should be placed as soon as possible after factor in choosing between partial and full pulpot­ endodontic treatment; and (6) endodontic retreat­ omy.160 The amount of time elapsed since the injury ment should be considered for teeth with a coronal often affects pulpal prognosis. The sooner the tooth seal that has been compromised for longer than 3 is treated, the better the prognosis. months.159 If these recommendations are followed, many enodontic and periodontal complications can Crown-root fracture and should be prevented. This type of fracture is usually oblique and involves both crown and root. It includes enamel, dentin, and Trauma cementum and may or may not include the pulp. Trauma to teeth and alveolar bone may involve the Crown-root fractures can affect molars and premo­ pulp and the periodontal ligament. Both tissues lars as well as anterior teeth. Cusp fracture extend­ can be affected either directly or indirectly. Dental ing subgingivally is a common finding that often injuries may take many shapes but generally can be presents a diagnostic and clinical challenge.160

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Treatment depends on the severity of the fracture for minor subluxations. If mobility is severe, stabiliza­ and may vary from removal of the fractured tooth tion of the tooth is necessary. fragment and restoration to endodontic treatment In extrusive luxation, the tooth has been partially to periodontal treatment and/or surgical proce­ displaced from the socket and increased mobility is dures. Sometimes the prognosis is poor and the found. Radiographs also reveal displacement. The tooth has to be extracted. Because of the complex­ pulp usually does not respond to vitality tests, and ity of this injury, a team approach involving endo­ root canal treatment is required once irreversible dontists, periodontists, orthodontists, and pros­ pulpitis is diagnosed.160 The tooth requires repo­ thodontists is highly recommended.160 sitioning and splinting, usually for a 2- to 3-week period. Root fracture In lateral luxation, the tooth has been displaced This type of fracture typically involves cementum, away from its long axis. Percussion sensitivity may dentin, and pulp. It may be horizontal or transverse. or may not be present. A metallic sound on percus­ Clinically, root fracture may often cause mobility of sion indicates that the root has been forced into the the segment coronal to the fracture as well as pain alveolar bone.160 Tr eatment includes repositioning on biting. Often, a periodontal defect or a sinus tract and splinting. Lateral luxations that involve bony is associated with the fractured root. Radiographi­ fractures usually require up to 8 weeks of splinting. cally, a root fracture can only be visualized if the Endodontic treatment should be performed only x-ray beam passes through the fracture line. Hori­ when a definite diagnosis of irreversible pulpitis or zontal and oblique root fractures are easier to detect pulpal necrosis is established. radiographically, while the diagnosis of vertical root During intrusive luxation, the tooth is forced fractures is more challenging. Advanced imaging into the sockets in an axial direction. The tooth has technology may prove beneficial for diagnostic pur­ decreased mobility resembling ankylosis.160 Treat­ poses.163 ment depends on root maturity. If the root is not Treatment, when feasible, usually includes repo­ completely formed and presents with an open apex, sitioning of the coronal segment and stabilization it may reerupt. In such cases, root canal treatment is by splinting.160 A flexible splint using orthodontic or not necessary because the pulp may revascularize.166 nylon wire and acid-etched resin for periods of up If the tooth is fully developed, active extrusion is to 12 weeks will enhance pulpal and periodontal indicated. In such cases, root canal treatment is indi­ repair.164 Teeth with fractured roots do not necessar­ cated because pulpal necrosis develops in almost all ily require root canal treatment if healing takes place cases.166 with no evidence of pulpal disease.165 Avulsion

Luxation In avulsion, the tooth is totally displaced from its This category involves different types of tooth dis­ alveolar socket. If the tooth is reimplanted soon placement injuries. It includes concussion, sublux­ after avulsion, the periodontal ligament has a good ation, extrusive luxation, lateral luxation, and intru­ chance of healing.160 Extraalveolar time and the sive luxation. Generally, the more severe the luxation storage media used to transport the tooth are criti­ injury, the greater the damage to the periodontium cal factors for successful reimplantation. Root canal and to the dental pulp.160 treatment within 10 days of injury and the degree of In a concussion injury, the tooth is only sensitive recovery of the periodontal ligament cells will deter­ to percussion. There is no increase in mobility, and mine long-term success. no radiographic changes are found. The pulp may respond normally to vitality tests, and no immediate Perforation treatment is usually necessary.160 When root perforation occurs, communications In a subluxation injury, the tooth is sensitive to between the root canal system and either periradicular percussion and also has increased mobility. Often tissues or the oral cavity may often lead to treatment sulcular bleeding is observed, indicating damage to failure. Root perforations may result from extensive the periodontal ligament. Radiographic findings are caries lesions, resorption, or operator error during root unremarkable, and the pulp may respond normally canal instrumentation or post preparation.167·168 to vitality tests.160 No treatment is usually required

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The prognosis for a tooth with a perforated root As long as the epithelial attachment remains depends on the size and location of the perforation, intact, the periodontium remains healthy. However, time of diagnosis and treatment, degree of periodon­ once this attachment is breached and the groove tal damage, and the sealing ability and biocompat­ becomes contaminated, a self-sustaining infrabony ibility of the repair material.169 Treatment success pocket can be formed along its entire length. This depends mainly on immediate sealing of the per­ fissurelike channel provides a nidus for accumulation foration and appropriate infection control. Several of bacterial biofilm and an avenue for the progres­ materials have been recommended for sealing root sion of periodontal disease that may also affect the perforations, including mineral trioxide aggregate, pulp. Radiographically, the area of bone destruction SuperEBA (Bosworth), Cavit (3M ESPE), IRM (Caulk follows the course of the groove.180 Dentsply), glass ionomers, composite resins, and From a diagnostic standpoint, the patient may amalgam.170-174 To day, mineral trioxide aggregate is present with symptoms of a periodontal abscess the most widely used material. or a variety of asymptomatic endodontic condi­ An excellent and conservative treatment modal­ tions. If the condition is purely periodontal, it can ity for perforations, root resorptions, and certain be diagnosed by visually following the groove to root fractures is controlled root extrusion.175 The the gingival margin and by probing the depth of the procedure has a good prognosis and a low risk of pocket, which is usually tubular and localized to this relapse, and its versatility has been demonstrated in one area, as opposed to a more generalized peri­ multiple clinical situations.17&-178 It can be performed odontal problem. The tooth will respond to pulpal either immediately or over a few weeks, depend­ vitality testing. Bone destruction that follows the ing on each individual case. The goal of controlled groove vertically may be apparent radiographically. root extrusion is to modify the soft tissues and bone; If this condition is also associated with endodontic therefore, the technique is used to correct gingival disease, the patient may present clinically with any discrepancies and osseous defects at periodontally of the spectrum of endodontic symptoms. involved teeth.176 It is also used in the management The prognosis of root canal treatment in such of unrestorable teeth. cases is guarded, depending on the apical extent of The objective of forced eruption in prostheti­ the groove. The clinician must look for the groove cally compromised endodontically treated teeth is to because it may have been altered by a previous allow the restoration of a subcrestal defect by elevat­ access opening or restoration placed in the access ing the defect to a point where access is no longer cavity. The appearance of a teardrop-shaped area a problem.179 In all cases, the epithelial attachment on the radiograph should immediately arouse suspi­ remains at the level of the cementoenamel junction. cion. The developmental groove may actually be vis­ Forced eruption also presents a good alternative ible on the radiograph. If so, it will appear as a dark to crown lengthening because it Pr. events esthetic vertical line. This condition must be differentiated alterations and unnecessary reduction of bony sup­ from a vertical fracture, which may have a similar port of adjacent teeth. radiographic appearance. Tr eatment consists of flattening the groove with a Developmental malformation bur, placing bone substitutes, and surgically manag­ Te eth with developmental malformations tend to ing the soft tissues and underlying bone. A clinical fail to respond to periodontal and/or endodontic case using Emdogain (Straumann) as a treatment treatment when they are directly associated with an adjunct was recently described.180 Radicular grooves invagination or a vertical developmental radicular are self-sustaining infrabony pockets, and therefore groove. Such conditions can lead to an untreatable scaling and root planing will not suffice. Although periodontal condition. These grooves usually begin the acute nature of the problem may be alleviated in the central fossa of maxillary central and lateral initially, the source of the chronic or acute inflam­ incisors, crossing over the cingulum and continuing mation must be eradicated by a surgical approach. apically down the root for varying distances. Such a Occasionally, the tooth has to be extracted because groove is probably the result of an attempt of the of its poor prognosis. tooth germ to form another root.

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Fig 16-15 Primary endodontic disease in a mandibular first molar with a necrotic pulp. (a) Preoperative radiograph showing a periradicular radiolucency associated with the distal root. (b) Clinically, a deep, narrow buccal periodontal defect can be probed. (c) Radiograph taken 1 year after root canal therapy. Resolution of the perira­ dicular bony radiolucency is evident. (d) Clinical appearance 1 year posttreatment. The buccal defect has healed and probing is normal.

I Differential Diagnosis essential that the clinician insert a gutta-percha cone, or another tracking instrument, in the sinus tract and take one or more radiographs to determine the origin For differential diagnostic and treatment purposes, of the lesion. When the pocket is probed, it is narrow so-called endo-perio lesions are best classified as and lacks width. A similar situation occurs when drain­ endodontic, periodontal, or combined diseases.181 age from the apex of a molar tooth extends coro­ These include primary endodontic diseases, primary nally into the furcation area. This may also occur in the periodontal diseases, and combined diseases. The presence of lateral canals extending from a necrotic combined diseases include primary endodontic dis­ pulp into the furcation area.181 ease with secondary periodontal involvement, pri­ Primary endodontic diseases usually heal follow­ mary periodontal disease with secondary endodon­ ing root canal treatment (Fig 16-15). The sinus tract tic involvement, and true combined diseases. extending to the gingival sulcus or furcation area dis­ This classification is based on the theoretic path­ appears at an early stage once the affected necrotic ways explaining how these radiographic lesions are pulp has been removed and the root canals have formed. By understanding the pathogenesis, the been well cleaned, shaped, and obturated.181 clinician can then suggest an appropriate course of treatment and assess the prognosis. Once the lesions progress to their final involvement, they pres­ Primary periodontal disease ent a similar radiographic picture and the differential diagnosis becomes more challenging. These lesions are caused primarily by periodontal pathogens. In this process, chronic marginal peri­ odontitis progresses apically along the root surface. Primary endodontic disease In most cases, pulpal vitality tests indicate a clinically normal pulpal reaction (Figs 16-16 and 16-17). There is An acute exacerbation of a chronic apical lesion frequently an accumulation of plaque and calculus, in a tooth with a necrotic pulp may drain coronally and the pockets are wider. through the periodontal ligament into the gingival The prognosis depends on the stage of periodon­ sulcus. This condition may simulate clinically the pres­ tal disease and the efficacy of periodontal treatment. ence of a periodontal abscess. In reality, it is a sinus The clinician must also be aware of the radiographic tract of pulpal origin that opens through the peri­ appearance of periodontal disease associated with odontal ligament area. For diagnostic purposes, it is developmental radicular anomalies (Fig 16-18).

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Fig 16-16 Primary periodontal disease in a mandibular second molar. The patient has been referred for endodontic therapy. (a) Preoperative radiograph revealing periradicular radiolucency. The tooth responds normally to pulpal sensitivity tests. The referring dentist, however, insisted that endodontic therapy be done. (b) Photo­ micrograph of pulp tissue removed during treatment. Note the normal appearance of the pulp (H&E stain; original magnification X40). (c) Higher-magnification photo­ micrograph showing normal cellular components as well as blood microvasculature (H&E stain; original magnification x 100). (d) Postoperative radiograph. The tooth was subsequently lost to periodontal disease.

Fig 16-17 Primary periodontal lesion simulating an endodontic lesion. (a) Radiograph of a mandibular first molar revealing a periradicular radiolucency and periapical resorption. (band c) Buccal and lingual views, respectively, of the affected tooth. Note the gingival swelling and evidence of periodontal disease. In addition, an occlusal restoration is present close to the pulp chamber. Despite the clinical and radiographic appearances, the pulp responds normally to vitality testing procedures, indicating that the radiolucency, resorption, and gingival swelling are of periodontal origin. (d) Microphotograph showing the floor of the pulp chamber and entrance to the mesial canal, which contain normal pulp tissue (H&E stain; original magnification X40).

Fig 16-18 Primary periodontal disease in a maxillary second premolar (a) Radiograph showing alveolar bone loss and a periapical lesion. Clinically, a deep, narrow pocket is present on the mesial aspect of the root. There is no evidence of caries, and the tooth responds normally to pulpal sensitivity tests. (b) Radiograph showing pocket tracking with a gutta-percha cone to the apical area. The tooth will be extracted. (c) Clinical view of the extracted tooth with the attached lesion. Note the pres­ ence of a deep mesial radicular developmental groove. (d) Photomicrograph of the apex of the tooth with the attached lesion (H&E stain; original magnification X40). (e and f) Higher-magnification photomicrographs showing the inflammatory lesion, cementum and dentin resorption, and osteoclasts (H&E stain; original magnification x 100). (g and h) Histologic sections of the pulp chamber, revealing uninflamed pulp, the odontoblastic layer, and intact predentin (H&E stain; original magnification X40 and x 200, respectively).

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Fig 16-19 Primary endodontic disease with secondary periodontal involvement in a mandibular first molar. (a) Preoperative radiograph demonstrating an interradicular defect extending to the apical region of the mesial root. (b) Radiograph taken at completion of root canal therapy. (c) One­ year follow-up radiograph showing reso­ lution of most of the periradicular lesion; a bony defect remains at the furcal area. Endodontic treatment alone has not yielded complete healing of the defect. Periodontal treatment is necessary for further healing of the furcal area and inflamed gingival tissues.

Combined disease and repair the defect with an appropriate restorative material. In deeper perforations, or in the roof of the Primary endodontic disease with secondary furcation, immediate repair of the perforation has periodontal involvement a better prognosis than management of an infect­ If suppurating primary endodontic disease remains ed one. The use of mineral trioxide aggregate in untreated, it may become secondarily involved such cases may enhance cementa! healing following with marginal periodontal breakdown (Fig 16-19). immediate perforation repair.182 Plaque forms at the gingival margin of the sinus Root fractures may also present as primary endo­ tract and leads to marginal periodontitis. The treat­ dontic lesions with secondary periodontal involve­ ment and prognosis of the tooth are different when ment. These typically occur on endodontically plaque or calculus is present compared to when treated teeth, often those with posts and crowns. the tooth exhibits only primary endodontic disease. The signs may range from a local deepening of a The tooth now requires both endodontic and perio­ periodontal pocket to more acute periodontal dontal treatments. If the endodontic treatment is abscess formation. Root fractures have also become adequate, the prognosis depends on the severity of an increasing problem with molar teeth that have the marginal periodontal damage and the efficacy of been treated by root resection.1B-186 periodontal treatment. With endodontic treatment alone, only part of the lesion will heal to the level of Primary periodontal disease with secondary the secondary periodontal lesion. In general, heal­ endodontic involvement ing of the tissues damaged by suppuration from the The apical progression of a periodontal pocket may pulp can be anticipated.181 continue until the apical tissues are involved. In this Primary endodontic lesions with secondary perio­ case, the pulp may become necrotic as a result of dontal involvement may also occur as a result of root infection entering via lateral canals or the apical fora­ perforation during root canal treatment or where men (Fig 16-20). In single-rooted teeth, the prognosis pins or posts have been misplaced during coronal is usually poor. In molar teeth, the prognosis may be restoration. Symptoms may be acute, with periodon­ better: Because not all the roots may suffer the same tal abscess formation associated with pain, swell­ loss of supporting tissues, root resection can be con­ ing, purulent exudate, pocket formation, and tooth sidered as a treatment alternative. mobility. A more chronic response may sometimes The effect of progressive periodontitis on the occur without pain; this involves the sudden appear­ vitality of the pulp is controversial.4G-41.43 If the blood ance of a pocket with bleeding on probing or puru­ supply circulating through the apex is intact, the pulp lent exudate. has good prospects for survival. It was reported that When the root perforation is situated close to pulpal changes resulting from periodontal disease the alveolar crest, it may be possible to raise a flap are more likely to occur when the apical foramen is

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Fig 16-20 Primary periodontal disease with secondary endodontic involvement in a maxillary premolar. (a) Radiograph showing bone loss in one­ third of the root and a separate periapical radiolu­ cency. The crown is intact, but pulpal sensitivity tests are negative. (b) Radiograph taken immediately after root canal therapy, showing sealer in a lateral canal that had been exposed because of bone loss.

Fig 16-21 True combined endodontic-periodontal disease in a Fig 16-22 True combined endodontic-periodontal disease. (a) Radiograph showing bone mandibular first molar. Radiograph showing separate progression loss in two-thirds of the root. Calculus and a separate periapical radiolucency are present. (b) of endodontic disease and periodontal disease. The tooth had Clinical examination revealing the coronal color change of the involved tooth and pus exuding remained untreated, and, consequently, the two lesions joined from the gingival crevice. The results of pulpal sensitivity tests were negative. together.

involved.43 In these cases, bacteria originating from True combined disease the periodontal pocket are the source of root canal True combined endodontic-periodontal disease infection. A strong correlation between the presence occurs with less frequency. It is formed when an of microorganisms in root canals and their presence endodontic disease progressing coronally joins with in periodontal pockets of advanced periodontitis has an infected periodontal pocket progressing apical­ been demonstrated.187·188 Support for this concept ly.17·189 The degree of attachment loss in this type of has come from research in which cultured samples lesion is invariably large and the prognosis guarded obtained from the pulp tissue and radicular dentin of (Fig 16-21). This is particularly true in single-rooted periodontally involved human teeth showed bacterial teeth (Fig 16-22). In molar teeth, root resection can growth in 87% of the teeth.40-41 be considered as a treatment alternative if not all The treatment of periodontal disease can also roots are severely involved. Sometimes, supplemen­ lead to secondary endodontic involvement. Lateral tary surgical procedures are necessary (Fig 16-23). canals and dentinal tubules may be opened to the In most cases, periradicular healing may be antici­ oral environment by curettage, scaling, or surgi­ pated following successful endodontic treatment. cal flap procedures. It is possible for a blood vessel The periodontal tissues, however, may not respond within a lateral canal to be severed by a curette and well to treatment, and tooth retention will depend for microorganisms to be pushed into the area dur­ on the severity of the combined disease. ing treatment, resulting in pulpal inflammation and The radiographic appearance of combined necrosis. endodontic-periodontal disease may be similar to

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Fig 16-23 True combined endodontic-periodontal disease in a mandibular first molar. (a) Preoperative radiograph showing periradicular radiolucencies. The results of pulpal sensitivity tests were negative. (b) Immediate postoperative radiograph of the molar after nonsurgical endodontic treatment. (c) Six-month follow-up radiograph, revealing no evidence of healing. A gutta-percha cone is inserted in the buccal gingival sulcus. (d) Treatment of the root surfaces and removal of the periradicular lesion. (e) One-year follow-up radiograph, demon­ strating evidence of active healing.

that of a vertically fractured tooth. A fracture that place following root canal treatment will determine has invaded the pulp space, with resultant necrosis, the retrospective classification. In the absence of may also be labeled a true combined lesion and yet adequate healing, further periodontal treatment is not be amenable to successful treatment. If a sinus indicated. tract is present, it may be necessary to raise a flap to The prognosis and treatment of each endodontic­ determine the etiology of the lesion. periodontal disease type varies. Primary endodontic disease should only be treated by endodontic treat­ ment and has a good prognosis. Primary periodontal disease should only be treated by periodontal thera­ I Prognosis py. In this case, the prognosis depends on the severity of the periodontal disease and the patient's response. Primary endodontic disease with secondary perio­ Treatment prognosis depends primarily on the diag­ dontal involvement should first be treated with en­ nosis of the specific endodontic and/or periodontal dodontic treatment. Treatment results should be disease. The main factors to consider for treatment evaluated in 2 to 3 months, and only then should planning are pulpal vitality and the type and extent periodontal treatment be considered. This sequence of the periodontal defect. Diagnoses of primary of treatment allows sufficient time for initial tissue endodontic disease and primary periodontal dis­ healing and better assessment of the periodontal ease usually present little or no clinical difficulty. In condition.15·190 It also reduces the potential risk of primary endodontic disease, the pulp is infected and introducing bacteria and their by-products during nonvital. On the other hand, in a tooth with primary the initial healing phase. In this regard, it has been periodontal disease, the pulp is vital and responsive suggested that aggressive removal of the periodon­ to testing. However, primary endodontic disease tal ligament and underlying cementum during inter­ with secondary periodontal involvement, primary im endodontic therapy can adversely affect perio­ periodontal disease with secondary endodontic dontal healing.191 Areas of the roots that are not involvement, and true combined disease are clini­ aggressively treated show unremarkable healing.191 cally and radiographically very similar. The prognosis of primary endodontic disease If a lesion is diagnosed and treated as primary with secondary periodontal involvement depends endodontic disease because of a lack of evidence primarily on the severity of periodontal involve­ of marginal periodontitis, and if there is soft tissue ment, the periodontal treatment, and the patient's healing on clinical probing and bony healing on a response. Primary periodontal disease with sec­ recall radiograph, a valid retrospective diagnosis can ondary endodontic involvement and true com­ then be made. The degree of healing that has taken bined endodontic-periodontal disease require both

392 www.shayanNemodar.com References

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The fate and the role of bacteria left in lowing crown cementation. J Periodontol 1977;48:294-297. root dentinal tubules. Int Endod J 1995;28:95-99. 124. Mincer HH, McCoy JM, Turner JE. Pulse granuloma of the alveolar ridge. 150. Bergenholtz G, Lekholm U, Milthon R, Heden G, Odesjo B, Engstrom B. Oral Surg Oral Med Oral Pathol 1979;48: 126-130. Retreatment of endodontic fillings. Scand J Dent Res 1979;87:217-224. 151. Saunders WP, Saunders EM. Coronal leakage as a cause of failure in root canal therapy: A review. Endod DentTraumatol 1994; 10:10 5-108.

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152. Madison S, Wilcox LR. An evaluation of coronal microleakage in endodonti­ 173. Dazey S, Senia ES. An in vitro comparison of the sealing ability of materials cally treated teeth. Part Ill. In vivo study. J Endod 1988;14:455 -458. placed in lateral root perforations. J Endod 1990;16: 19-23. 153. Ray HA,Trope M. Periapical status of endodontically treated teeth in relation 174. Lee SJ, Monsef M, Torabinejad M. Sealing ability of a mineral triox­ to the technical quality of the root filling and the coronal restoration. Int ide aggregate for repair of lateral root perforations. J Endod 1993; 19: Endod J 1995;28:12-18. 541-544. 154. Saunders WP, Saunders EM. Assessment of leakage in the restored 175. Simon JH. Root extrusion-rationale and techniques. Dent Clin North Am pulp chamber of endodontically treated multirooted teeth. Int Endod J 1984;28:909-921. 1990;23:28-33. 176. Stevens BH, Levine RA. Forced eruption: A multidisciplinary approach for 155. Wilcox LR, Diaz-Arnold A. Coronal leakage of permanent lingual form, function, and biologic predictability. Compend Cantin Educ Dent access restorations in endodontically treated anterior teeth. J Endod 1998;1 9:994-1010. 1989;12:584 -587. 177. Villat C, Machtou P, Naulin-lfi C. Multidisciplinary approach to the immediate 156. Goldman M, Laosonthorn P, White RR. Microleakage-Full crowns and the esthetic repair and long-term treatment of an oblique crown-root fracture. dental pulp. J Endod 1992; 18:473-475. Dent Traumatol 2004;20:56-60. 157. White SN, Yu Z, Tom JF, Sangsurasak S. In vivo microleakage of luting 178. Emerich-Poplatek K, Sawicki L, Badal M, Adamowitz-Klepalska B. Forced cements for cast crowns. J Prosthet Dent 1994;71:333-338. eruption after crown/root fracture with a simple and aesthetic method 158. Patel S, Saunders WP, Burke F J. Microleakage of dentin bonded crowns using the fractured crown. Dent Traumatol 1995;21: 165-169. placed with different luting materials. Am J Dent 1997;10:179-183. 179. Simon JH, Lythgoe JB, Torabinejad M. Clinical and histological evaluation 159. Heling I, Gorfil C, Slutzky H, Kopolovic K, Zalkind M, Slutzky-Goldberg I. of extruded endodontically treated teeth in dogs. Oral Surg Oral Med Oral Endodontic failure caused by inadequate restorative procedures: Review Pathol 1980;50:361-371. and treatment recommendations. J Prosthet Dent 2002;87:674-678. 180. Al-Hezaimi K, Naghshbandi J, Simon JH, Oglesby S, Rotstein I. Successful 160. Bakland LK, Andreasen FM, Andreasen JO. Management of traumatized treatment of a radicular groove by intentional replantation and Emdogain teeth. In: Walton RE, Torabinejad T (eds). Principles and Practice of End­ therapy. DentTraumatol 2004;20:226-228. odontics, ed 3. Philadelphia: Saunders, 2002:445-465. 181. Rotstein I, Simon JH. The endo-perio lesion: A critical appraisal of the dis­ 161. Andreasen JO, Andreasen FM, Skeie A, Hj0rting-Hansen E, Schwartz 0. ease condition. Endod Topics 2006; 13:34-56. Effect of treatment delay upon pulp and periodontal healing of traumatic 182. Pitt Ford TR, Torabinejad M, McKendry D, Hong CU, Kariyawasam SP. Use of dental injuries. Dent Traumatol 2002;18: 116-128. mineral trioxide aggregate for repair of furcal perforations. Oral Surg Oral 162. Andreasen FM, Flugge E, Daugaard-Jensen J, Munksgaard EC.Treatment of Med Oral Pathol Oral Radial Endod 1995;79:756-763. crown fractured incisors with laminate veneer restorations. An experimen­ 183. Ross IF, Thompson RH Jr. A long term study of root retention in the tal study. Endod DentTraumatol 1992;8:30-35. treatment of maxillary molars with furcation involvement. J Periodontal 163. Nair MK, Nair UDP, Grondahl HG, Webber RL, Wallace JA. Detection of arti­ 1978;49:238-244. ficially induced vertical radicular fractures using tuned aperture computed 184. Langer B, Stein SD, Wagenberg B. An evaluation of root resections: A ten­ tomography. Eur J Oral Sci 2001;109:375-379. year study. J Periodontol 1981;52:719-722. 164. Andreasen FM, Andreasen JO, Bayer T. Prognosis of root-fractured per­ 185. Carnevale G, Pontoriero R, di Febo G. Long-term effects of root-resective manent incisors: Prediction of healing modalities. Endod Dent Traumatol therapy in furcation-involved molars. A 10-year longitudinal study. J Clin 1989;5:1 l-22. Periodontol 1998;25:209-214. 165. Cvek M, Andreasen JO, Borum MK. Healing of 208 intra-alveolar root frac­ 186. Blomlof LB, Jansson L, Appelgren R, Ehnevid H, Lindskog S. Progno­ tures in patients aged 7-17 years. Dent Traumatol 2001; 17:53-62. sis and mortality of root-resected molars. Int J Periodont Restor Dent 166. Andreasen FM. Pulpal healing after luxation injuries and root fractures in 1997; 17:190 -201. the permanent dentition. Endod Dent Traumatol 1989;5:111 -131. 187. Kipioti A. Nakou M, Legakis N, Mitsis F. Microbiological finding of infected 167. Torabinejad M, Lemon RL. Procedural accidents. In: Walton RE, Torabinejad root canals and adjacent periodontal pockets in teeth with advanced peri­ M. Principles and Practice of Endodontics, ed 2. Philadelphia: Saunders, odontitis. Oral Surg Oral Med Oral Pathol 1984;58:213-220. 1996:306-323. 188. KobayashiT, Hayashi A, Yoshikawa R, Okuda K, Hara K.The microbial flora 168. Kvinnsland I, Oswald RJ, Halse A, Grnnningsaeter AG. A clinical and from root canals and periodontal pockets of nonvital teeth associated with roentgenological study of 55 cases of tooth perforation. Int Endod J advanced periodontitis. Int Endod J 1990;23: 100-106. 1989;22:75-84. 189. JOE Editorial Board. Endodontic-periodontal interrelationships: An online 169. Fuss Z, Trope M. Root perforations: Classification and treatment choices study guide. J Endod 2008:34(5 suppl):e71-e77. based on prognostic factors. Endod Dent Traumatol 1996; 12:255-264. 190. Chapple IL, Lumley PJ. The periodontal-endodontic interface. Dent Update 170. Jew RC, Weine FS, Keene JJ, Smulson MH. A histologic evaluation of peri­ 1999;26:331-334. odontal tissues adjacent to root perforations filled with Cavit. Oral Surg 191. Blomlof LB, Lindskog S, Hammarstrom L. Influence of pulpal treatments Oral Med Oral Pathol 1982;54:124 -135. on cell and tissue reactions in the marginal periodontium. J Periodontal 171. Oynick J, Oynick T. Treatment of endodontic perforations. J Endod 1988;59:577-583. 1985;11:191-192. 172. Roane JB, Benenati FW. Successful management of a perforated mandibu­ lar molar using amalgam and hydroxylapatite. J Endod 1987;13:400-404.

396 www.shayanNemodar.com Root Resorption

Linda G. Levin, DDS, PhD

Root resorption is a rare occurrence in permanent this hypothesis in that it has long been noted that teeth. Unlike bone, which undergoes resorption and osteoclasts will not adhere to unmineralized matrix.8 apposition as part of a continual remodeling pro­ Recent studies indicated that the polarity of osteo­ cess, the roots of permanent teeth are not normally clasts is regulated by their actin cytoskeleton. Non­ resorbed.1 Only resorption of primary teeth during resorbing osteoclasts form podosomes at the cell exfoliation is considered physiologic.2·3 periphery when they come into contact with unmin­ eralized substrates. Conversely, on contact with min­ eralized extracellular matrices, the actin cytoskeleton of an actively resorbing osteoclast is reorganized I Mechanisms of Resorption into a sealing zone. Formation of this sealing zone is mediated by the presence of apatite.9-11 Osteoclasts bind to extracellular proteins con­ Even under conditions that would normally result in taining the arginine-glycine-aspartic acid (RGD) bone resorption, such as alterations in oxygen ten­ sequence of amino acids12 via specific membrane sion, hormonal fluctuations, locally produced chemi­ receptors known as integrins. lntegrins are a fam­ cal mediators, or electrical currents, the root is resis­ ily of cell-surface adhesion glycoproteins containing tant to resorption on both its external and internal different a and f3 subunits (see chapter 11). It is gen­ surfaces.4 Although several hypotheses have been erally accepted that the avf33 integrin plays a cen­ proposed, the exact mechanism by which the resorp­ tral role in osteoclast polarization13 and adhesion.14 tive process is inhibited is unknown. One hypothesis Extracellular proteins containing the RGD peptide maintains that the remnants of Hertwig's epithelial sequence are bound to calcium salt crystals on min­ root sheath surround the root like a net and impart eralized surfaces and serve as osteoclast binding resistance to resorption and subsequent ankylosis.5·6 sites. In its normal state, the most external aspect While a protective role for Hertwig's epithelial root of cementum is covered by a layer of cemento­ sheath has not been established, there is evidence blasts over a zone of unmineralized cementoid and that these cells are involved in cementa! repair sub­ therefore does not present a surface satisfactory for sequent to resorption by sequential elaboration of osteoclast binding. Internally, the dentin is covered specific matrix proteins, namely osteopontin, bone by predentin matrix, a similarly organic surface (Fig morphogenetic protein 2, and ameloblastin.7 17-1). Thus, the lack of RGD proteins in both cemen­ A second hypothesis is based on the premise tum and predentin reduces osteoclast binding and that the covering of cementum and predentin on confers resistance to resorption. Numerous studies dentin is essential for the resistance of the den­ lend support to this theory.1S-1s It has also been dem­ tal root to resorption. There is some support for onstrated in cases of extensive external root resorp-

397 www.shayanNemodar.com Root Resorption

Fig 17-1 (a and b) Histologic appearance of pulp, periodontal ligament, and adjacent den­ .. tin. The precementum (PC) and predentin (PD) have antiresorptive properties. If the intermediate cementum (IC) is penetrated, any pulpal toxins that may be present will cause periodontal inflam­ mation with bone and root resorption (hematoxylin­ eosin [H&E] stain; original magnification X25).

Fig 17-2 (a and b) Histologic appearance of a molar with extensive external root resorption. Although the dentinal resorption is extensive, the odontoblast-predentin layer (arrows)is intact (H&E stain; original magnification x 50 and x 100, respectively).

tion that the circumpulpal dentin in close proximity Binding of OPG reduces RANKL concentration and to the predentin is spared, even though most of the thereby inhibits its ability to bind to receptor activa­ peripheral dentin may have been resorbed (Fig tor of nuclear factor KB (RANK) receptors on the sur­ 17-2). Conversely, damage to cementum or preden­ face of osteoclast precursors (circulating monocytes) tin increases the probability of osteoclast-induced and stimulate osteoclast production (osteoclasto­ resorption, which can occur in teeth damaged dur­ genesis).24-28 ing avulsions or other traumatic injuries. Localized Cementoblasts have been shown to constitutively replacement resorption and mild to severe external express OPG in vitro. Furthermore, co-cultures of inflammatory root resorption with pulpal involve­ cementoblasts with mononuclear precursor cells ment have been demonstrated when the cementum diminished the effects of RANKL on osteoclasto­ was damaged by inadvertent contact of root sur­ genesis.29 Human gingival fibroblasts, human peri­ faces with miniscrew implants employed for anchor­ odontal ligament cells, and human pulp cells also age during orthodontic treatment.19-21 Although this produce OPG.29-32 hypothesis has both experimental support and clini­ Finally, another hypothesis applicable to certain cal implications, other hypotheses have also been types of external root resorption involves the bar­ advanced. rier formed by the less highly calcified intermediate Another possible explanation for the relative cementum or the cementodentin junction33-35 (Fig resistance of teeth to resorption is that intrinsic fac­ 17-3). The intermediate cementum, the innermost tors found in predentin and cementum, such as layer of cementum, creates a barrier between the amelogenin or osteoprotegerin (OPG), act as inhibi­ dentinal tubules and the periodontal ligament.36-38 tors of resorptive cells.22·23 OPG, a member of the Under normal circumstances, this barrier does not tumor necrosis factor (TNF) superfamily, has the abil­ allow irritants such as bacterial by-products to pass ity to inhibit osteoclast-mediated bone loss. OPG from an infected pulp space to stimulate an inflam­ acts as a decoy receptor by binding to the recep­ matory response in the adjacent periodontal liga­ tor activator of nuclear factor KB ligand (RANKL). ment. However, if the intermediate cementum is

398 www.shayanNemodar.com Mechanisms of Resorption

Odontoclast life cycle

Fig 17-3 Histologic appearance of a localized area of root resorption (RR) that has healed with new cementum (C) and periodontal ligament (PDL). The ini­ tial damage was caused by a mild local­ ized luxation injury (H&E stain; original magnification x 100).

avf lost or damaged, then proinflammatory mediators may diffuse from an infected pulp space into the RG periodontal ligament, setting up an inflammatory response and subsequent external inflammatory Fig 17-4 Odontoclast life cycle. Shaded boxes list molecules involved in root resorption. In addition, the collagen-rich bar­ osteoclast maturation, function, and demise. Tartrate-resistant acid phospha­ rier provided by intermediate cementum could pre­ tase (TRAP), calcitonin receptors (CTRs), vitronectin receptors (VTRs), carbonic vent the attachment of osteoclasts to mineralized anhydrase II (CAii), cathepsin K (CTPK), and vacuolar H+-adenosine triphos­ phatase (V-ATPase) are molecular markers for the mature elastic phenotype. dentin even when external resorption has occurred M-CSF, macrophage colony-stimulating factor. in the peripheral, more highly mineralized cemen­ tum. When the intermediate cementum is lost or damaged, the osteoclasts may continue to induce resorption in the underlying dentin in the presence of inflammatory stimulators, resulting in the progres­ sion of external inflammatory root resorption to the radicular dentin. These different hypotheses are not tors involved in pathologic root resorption are fewer, mutually exclusive, and their relative contributions to however, and are primarily or secondarily associ­ various clinical conditions may also vary depending ated with the inflammatory response to infection. on the circumstances of each case. It is known that inflammatory mediators are potent It is now well established that a strong inter­ stimulators of osteoclast and odontoclast recruit­ play among factors involved in hematopoiesis and ment and function. TNF, interleukins 1 (IL-1), 6, (IL-6), immune function are responsible for osteoclasto­ 11 (IL-11), and 17 (IL-17), and prostaglandin E2 influ­ genesis. The myeloid and B-cell transcription factor ence stromal cells to produce pro-osteoclastogenic PU.1 is the earliest identifiable determinant of the molecules (Fig 17-4). Receptor-ligand interactions osteoclast lineage39 and is actively involved in the perpetuate the process; these include RANK and regulation of [33 integrin expression during osteo­ RANKL, previously mentioned RGD-containing clast differentiation.40 Other factors involved include extracellular matrix molecules and avl33 integrin, and the lipopolysaccharide receptor CD14 and the early macrophage colony-stimulating factor and cFms. monocytic integrins CD11 b and CD11 c. CD11 b is Receptor-ligand binding initiates a cascade of sig­ one of the recognized markers of osteoclast precur­ naling intermediates (Src, TNF receptor-associated sors in humans.41 factor 6, and P13K), cytoplasmic phosphokinases Once recruited, a variety of mediators such as (protein kinase B [Akt], c-Jun N-terminal kinases, hormones, integrins, transcription factors, and cyto­ p38, and extracellular signal-regulated kinase), tran­ kines affect osteoclast differentiation, maturation, scription factors (c-Fos, c-Jun, nuclear factor KB, and and function41-43 (see chapter 16). The primary fac- nuclear factor of activated T cells, cytoplasmic 1 ),

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and effector molecules necessary for osteoclastic the fusion of monocytic precursors.42·58 Odontoclasts activity (matrix metalloproteinase 9 [MMP-9], vacu­ differ slightly from their bone-resorbing counterparts olar H+-adenosine triphosphatase [V-ATPase], and in that they are usually smaller, have fewer nuclei, cathepsin K). and have very small (if any) sealing zones.59 Nonethe­ Osteoclastic activity involves removal of both less, these cells are thought to represent a variant of the inorganic and organic components from the osteoclasts with morphologic differences that reflect mineralized tissue.44 Dissolution of the mineralized the nature of the resorption substrate as well as the component of bone and cementum by osteoclasts is resorption kinetics of the cells.42 largely dependent on acidification of the extracellu­ Dendritic cells, the mononuclear cells that initi­ lar resorption lacuna by V-ATPases within the ruffled ate the adaptive immune response, have previ­ border membranes of the osteoclasts.45•46 After dis­ ously been regarded as having limited phagocytic solution of the mineral phase, specific members of activity, although they share a common hematopoi­ two specific classes of proteolytic enzymes, cysteine etic lineage with the multinucleated bone-resorbing proteinases (cathepsin K) and matrix metallopro­ osteoclasts. Recent studies, however, have indi­ teinases (MMP-1, -2, and -9}, secreted by the osteo­ cated that immature dendritic cells have the poten­ clasts, contribute differentially to the degradation tial to transdifferentiate into osteoclasts, in a pro­ of the extracellular demineralized type I collagen cess regulated by innate and adaptive cytokines.60·61 matrix.47-50 Both human and murine dendritic cells have been Some of the mediators of inflammation-induced shown to be novel osteoclast precursors that are elastic function belong to the glycoprotein 130 able to generate osteoclasts more efficiently than (gp130) cytokine family that has been shown to monocytes.62 Because dendritic cells are present play a key role in bone remodeling.51 This family is in the dental pulp (see chapter 4), it is not known a pleomorphic group that shares a common signal if they may function also as precursors of elastic transducer (gp130) and includes cardiotrophin 1, cells that are responsible for internal resorption oncostatin M, ciliary neurotropic factor, IL-6, IL-11, of the canal space. On a cellular level, osteoclasts and leukemia inhibitory factor. Of these factors, IL-6 are usually large and have multiple nuclei. They and IL-11 appear to have the most profound effect possess a well-defined Golgi apparatus, numerous on hard tissue resorption, and IL-6 has been shown lysosomal vesicles, and high polarity.63 Characteris­ to stimulate osteoclastogenesis in the presence tic morphologic features of the osteoclast are the of IL-1 but not in the presence of anti-IL-1.52 This ruffled border, formed by membrane and cytoplas­ effect is dependent on the expression of the IL-6 mic undulations, and the sealing zone, consisting of receptor on osteoblastic cells and occurs in a dose­ the ventral surface of the osteoclast membrane in dependent manner.53 IL-6 also appears to reverse contact with the targeted bone or root surface. The the inhibitory effects of extracellular Ca2+ by reduc­ mature osteoclast is further defined by a series of ing the ability of osteoclasts to detect extracellular molecular markers, each representing genes integral Ca2+ concentrations and is expressed by cells of the to elastic functionM These include transcripts coding stromal/osteoblastic lineage.54 for tartrate-resistant acid phosphatases, calcitonin I L-11 is an osteoblast-derived mediator that receptors, vitronectin receptors, carbonic anhydrase induces prostaglandin synthesis and thereby triggers 11, cathepsin K, and V-ATPase.65 differentiation of elastic cells. Cells of the osteoclast Within the last few years, the dynamic interac­ phenotype have been shown to express the IL-11 tions between osteoclasts and the innate immune receptor gene, which in turn seems to be related system have increasingly been recognized, result­ sequentially to expression of the calcitonin receptor ing in a rapidly developing field of research that is gene, a recognized osteoclast differentiation mark­ known as osteoimmuno/ogy.66-71 There is increasing er.54 Furthermore, gp130 signal induction by IL-11 evidence that osteoclast precursors and osteoclasts appears to be necessary for IL-1-induced osteoclast modulate the differentiation of osteoblastic cells, formation.55-57 regulate hematopoietic stem cell movement from The singular defining feature of the mature the bone marrow to the bloodstream, and func­ osteoclast is functional, namely the ability to resorb tion as secretory cells that participate in immune calcified tissues. Morphologically, the osteoclast is responses. Osteoclasts also function as highly regu­ described as a multinucleated giant cell formed by lated innate immune cells of the bone that respond

400 www.shayanNemodar.com Role of Dental Pulp in Resorption

to stress and inflammatory changes in their micro­ and RhoA-dependent pathway) that mediates cyto­ environment. Their interactions with the immune skeletal rearrangement, ruffled border formation, system are mediated not only by the release of and substrate adhesion.75 Once the ruffled border cytokines and chemokines but also by direct cell-cell has been formed, the odontoclast secretes an acidic contact. solution containing proteolytic enzymes, specifically An understanding of the complex interactions carbonic anhydrase and V-ATPase, into the extra­ between osteoclasts and the immune system will cellular resorbing compartment to effect decalcifica­ 3 provide a scientific basis for future therapeutic tion.6 approaches to diseases related to both the bone During root resorption, organic matrix proteins and immune systems. In the context of root resorp­ and cytokines from the surrounding bone and den­ tion, elucidating the interaction of osteoclasts with tin are released locally into the gingival crevicular the immune system may, for example, improve the fluid. The concentrations of dentin phosphophoryn understanding of the pathogenesis and may provide and dentin sialoprotein were found to be higher in solutions to the treatment of patients with idiopathic the gingival crevicular fluid in human subjects with multiple subepithelial inflammatory root resorp­ severe root resorption. These two dentin-specific tion lesions. These were purported to be caused organic matrix proteins have been suggested as by transmission of feline viral infections from cats to biologic markers for monitoring root resorption dur­ humans.72.73 ing orthodontic treatment.76 Osteopontin, OPG, and A model for the process of root resorption can RANKL could also be detected in the gingival crevic­ be depicted based on what is known about odonto­ ular fluid derived from teeth with severe root resorp­ clasts combined with data extrapolated from studies tion. An increased RANKL-OPG ratio was found to of osteoclasts (see Fig 17-4). As previously men­ be correlated with an increase in bone resorption tioned, initiation of root resorption has two require­ activity during orthodontic tooth movement.77 ments: (1) removal of the protective layer (preden­ tin internally and precementum externally) of the root and (2) the presence of a noxious stimulus that results in an inflammatory response adjacent to the I Role of Dental Pulp in Resorption damaged external root surface. Given these condi­ tions, the first step in root resorption is binding of the odontoclast to its substrate. Because the focus of this book is the dental pulp Various RGD peptide-containing proteins (eg, and its interaction with other tissues, those types of osteopontin, bone sialoprotein, fibronectin, and vit­ resorption in which the pulp plays a major role are ronectin) have been shown to be involved in osteo­ discussed in detail. However, it is important to dis­ clast binding. Most notably, osteopontin has been cuss briefly additional common dental root resorp­ shown to play an important role in regulating osteo­ tions because this knowledge allows the practitioner clast recruitment and activation by binding to the to accurately differentiate these resorption phenom­ osteoclast integrin receptor avf33.13·14 Osteopontin ena and support correct diagnosis before treatment deficiency resulted in osteoclast suppression and is rendered. reduction in tooth resorption in a murine model.74 The pulp plays an essential role in two types of Osteopontin serves as a linker molecule so that one resorption. The first type of resorption is external domain is bound to apatite crystallites in exposed inflammatory root resorption. In external inflam­ dentin and another domain is bound to the integ­ matory root resorption, the necrotic infected pulp rin protein (avf33) extending from the osteoclast's provides the stimulus for periodontal inflamma­ plasma membrane. tion. If the cementum has been damaged and the

The binding of osteopontin to avl33 integ­ intermediate cementum is penetrated, as when the rin facilitates elastic cell adhesion and subse­ tooth undergoes a traumatic injury, the inflammatory quent establishment of the clear zone or extra­ stimuli in the pulp space are able to diffuse through cellular resorbing compartment. Osteopontin-avl33 the dentinal tubules and induce an inflammatory interaction with odontoclasts stimulates a second response over large areas of the periodontal liga­ messenger pathway (ie, gelsolin association with ment. Without cementa! protection, this will result in phosphatidylinositol-3-hydroxyl kinase via a pp60src- resorption of both tooth and bone.

401 www.shayanNemodar.com Root Resorption

The second type of resorption in which pulp tissue plays an important role is internal inflamma­ tory root resorption. In internal inflammatory root resorption, the inflamed pulp is the tissue involved in resorption of the root structure. The pathogenesis of internal root resorption is not completely under­ stood. One theory maintains that coronal necrotic infected pulp provides a stimulus for inflammation in the more apical parts of the pulp. An alternative the­ ory is based on the knowledge that apoptotic osteo­ cytes induce the secretion of osteoclastogenic cyto­ kines that enhance bone resorption.78.79 It is known that odontoblasts undergo apoptosis both in tooth

development as well as in response to certain types Fig 17-5 Active transient external inflammatory root resorption. Note the of trauma.8D-

402 www.shayanNemodar.com ExternalRoot Resorption

Fig 17-6 Histologic appearance of active osseous replacement (OR). Without Fig 17-7 Radiographic appearance an intermediate periodontal ligament, bone attaches directly to the root. Areas of osseous replacement. The bone that of active root resorption (RR) are seen in the bone and root (H&E stain; original is replacing root has a mottled appear­ magnification x 100). ance. Radiolucencies are not apparent in the adjacent bone.

from the socket wall and populate the damaged thorough review of these current areas of therapy root (Fig 17-6). The result is that bone comes in and research; the interested reader is encouraged to direct contact with the root, without the intermedi­ seek reviews on this aspect of care.86·87 ate cementum to serve as an attachment apparatus. This phenomenon is termed dentoalveolar anky/o­ sis84 (Fig 17-7). External root resorption caused by an Bone resorbs and forms physiologically through­ injury to the external root surface with out life. Once in direct contact with bone, dentin becomes part of the bone-remodeling process. an inflammatory component Osteoclasts resorb root structure, and the resorp­ tive lacunae are repopulated by osteoblasts, not There are four general types of inflammatory stimu­ odontoblasts or cementoblasts.85 The osteoblasts lus that cause external root resorption: (1) pressure­ then synthesize and deposit bone matrix directly on induced damage to the root surface, (2) microbial the denuded dentin, and mineralization ensues. The infection of the root canal system or periodontal sul­ resultant hard tissue is bone, not dentin or cemen­ cus, (3) sulcular infection, and (4) chemical damage tum. This process can continue until the entire root is secondary to bleaching.8B-90 replaced by bone. Treatment strategies for osseous replacement Pressure resorption are directed at avoiding or minimizing the Pressure both damages the cementum and pro­ initial inflammatory response. Five specific strategies vides a continuous stimulus for the resorbing cells. should be considered: (1) Prevention of the initial The most common example of this type of pres­ injury should be emphasized by counseling or advo­ sure resorption is root resorption caused by exces­ cating use of mouthguards for athletic endeavors; (2) sive forces of orthodontic tooth movement. Other treatment should minimize additional damage after examples are resorption caused by impacted teeth the initial injury; (3) pharmacologic interventions that and tumors. inhibit the initial inflammatory response should be Pressure resorption has been assumed to be exter­ considered; (4) the possibility of stimulating cemen­ nal, but this is not necessarily true. In orthodontics, for ta! (rather than osseous) healing should be con­ example, the process takes place at the apex of the sidered; and (5) interventions that reduce the rate tooth near the cementodentin junction. Because the of osseous replacement, when inevitable, should force affects the apical root, either the cementum or be considered. Space limitations preclude a more predentin may be damaged. Because the predentin

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weeks after the cessation of orthodontic treatment, although the use of light forces produced less root resorption and better repair than the use of heavy forces.102,103 The distance of movement also has an impact; movement over greater distances increases the prob­ ability of OIRR.104 Intrusive movements and lingual root torque tend to be associated with higher levels of root resorption because they concentrate forces at the apex.105·106 Bodily tooth m9vement, extrusion, and lingual tipping movement, by contrast, result in a lower incidence, presumably because the stress is evenly distributed over a larger area of the root dur­ Fig 17-8 Root resorption during active orthodontic tooth movement. Man­ ing these movements.96 dibular central incisors show apical external and internal resorption. In addition to factors relating to the mechanics of tooth movement, there are specific patient-related risk factors for OIRR. Patients who have short roots prior to orthodontic treatment or who show signs of root resorption before treatment are at higher risk for OIRR.97 In addition, there is mounting evi­ dence for a genetic predisposition to OIRR.101-110 may be affected also, it is not unusual to see radio­ A link has been made between a polymorphism in graphic evidence of internal apical resorption in the the IL-1 gene (IL1B allele 1) and the occurrence of active stage of the process (Fig 17-8). OIRR. Patients who are homozygous for /U B allele 1 In 1997, Bender and colleagues91 labeled this have a 5.6-fold greater risk for OIRR.111 The TNFRS­ type of resorption periapical replacement resorption F11A gene that encodes for a TNF receptor that is and offered a hypothetical explanation for it, sug­ involved in osteoclastogenesis represents another gesting that pulp neuropeptides may be involved candidate gene for OIRR.112 in periapical replacement resorption in both vital If OIRR is detected during active orthodontic and endodontically treated incisors. Their review treatment, it is recommended that treatment be indicated that apical resorption is significantly less halted for 2 to 3 months with passive archwires and frequent and less severe in endodontically treat­ bite. Severe OIRR may require cessation of ortho­ ed incisors than in untreated teeth. These findings dontic treatment indefinitely.113 are consistent with other studies that found endo­ dontically treated teeth were less likely to undergo Pulp space infection resorption during orthodontic therapy.92·93 The use of Pulp space infection represents the second general a calcium hydroxide interappointment dressing has type of inflammatory stimuli that can cause external recently been shown in a canine model to produce a root resorption. Pulp space infection can lead to favorable outcome on the repair of orthodontic root external root resorption in either the apical or lateral resorption in endodontically treated teeth.94 regions of the root. The classic example of pulp space Orthodontically induced inflammatory root resorp­ infection causing apical external root resorption is tion (OIRR) has been attributed to both treatment­ apical periodontitis with apical root resorption. and patient-related factors.92·95-98 Treatment-related The etiology for this form of apical external root factors include the duration of treatment, the resorption is infection of the root canal system. The magnitude of force exerted, the direction of tooth pulp of the tooth may become necrotic for many movement, and the method of movement.99 Pro­ reasons, but the predominant cause is a bacte­ longed orthodontic treatment may result in an rial challenge through caries (see chapters 10 and increased incidence and severity of apical root 14). When the pulp defenses are overcome, the resorption.100 The use of intermittent forces was pulp becomes necrotic and infected, and subse­ found to produce less OIRR than the use of con­ quently there is diffusion of microbes and their by­ tinuous forces.101 Root resorption continued for 4 products into the surrounding periodontium. In most

404 www.shayanNemodar.com External Root Resorption

Fig 17-9 Histologic appearance of apical resorption caused by an infected Fig 17-10 Tooth with external apical resorption caused by apical periodonti­ root canal. Chronic inflammation is present apically. Resorption of the external tis. The pulp is necrotic and infected. and internal aspects of the root can be seen (H&E stain; original magnification X100).

routine cases, the root surface is protected by its se. The radiographic appearance, as mentioned intact cementum, and communication will be primar­ earlier, is not detectable in most cases; however, ily through apical foramina or occasionally through when apparent, the radiolucencies are evident at accessory canals. the root tip and adjacent bone. Irregular shortening, Invariably, the periodontal inflammation is stumping, or thinning of the root tip is sometimes accompanied by slight resorption of the root at the observed (Fig 17-10). cementodentin junction. This resorption is usually The histologic appearance of a periapical lesion not apparent radiographically but is routinely visible may be either granulomatous or cystic.114•115 On upon histologic evaluation (Fig 17-9). It is not obvi­ the root surface, resorption of the cementum and ous why the apex of the root is not as well protected dentin results in a scalloped appearance of the root from the resorbing factors produced during the end (see Fig 17-9). Attempts at repair are often evi­ inflammatory response as are the other areas of the denced by the presence of the resorption lacunae, root. A simple explanation might be that inflamma­ resulting in resorptive and mineralization processes tion is confined to a small area at the apex of the observed adjacent to each other.4 root so that the concentration of resorbing factors The treatment protocol for external root resorp­ is so high that the resistance of the root to resorp­ tion with apical periodontitis should be directed tion is overcome. Another speculation is that the at removing the stimulus for the underlying inflam­ cementodentin junction at the apical foramen pro­ matory process, the microbes in the root canal vides an extremely thin protective layer compared system.116•117 If a thorough disinfection protocol is with the other areas of the root. It is also possible followed, an extremely high success rate can be that the cementum and dentin could fail to meet expected.118•119 At present, the treatment proto­ in a certain percentage of the cases, as with the col of choice is complete debridement of the root cementoenamel junction. Thus, the mineralized tis­ canal systems with sodium hypochlorite irrigation sue would be exposed, permitting attachment of the at the first visit. A creamy mix of calcium hydroxide elastic resorbing cells via the av�3 integrins to RGD­ is then introduced with a lentulo instrument. After containing peptides such as osteopontin. the intracanal medicament has been in place for at There are no clinical manifestations because api­ least 7 days, the root canal system is sealed. Recent cal root resorption is asymptomatic. Symptoms that research indicates that the canal may be obturated might lead to its diagnosis are associated with peri­ after the first visit if larger than currently accepted apical inflammation and not root resorption per instrumentation is used.120•121 When extensive resorp-

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Fig 17-12 Histologic appearance of inflammatory resorption revealing chronically inflamed tissue in relation to the resorbed root surface. Multinucle­ ated giant cells (asterisk) are present in the areas of active resorption on the root surface (H&E stain; original magnification x 100).

Fig 17-11 Radiographic appearance of external inflammatory resorption caused by pulpal infection. Note the radiolucencies in the root (R) and adjacent bone (B).

tion is present apically, the clinician should account colony-forming units and more than 80 strains124 (see for canal-altering pathologic processes when estab­ chapter 10). lishing a working length for canal debridement. Because a serious injury is required for pulpal Attempts should be made to instrument the full necrosis, the protective cementa! covering of the length of the remaining canal while a dentin shelf is root is usually damaged or lost as well. As described created to serve as a stop for the gutta-percha obtu­ in chapter 3, studies have shown that the loss of the ration. Apical closure techniques with long-term cal­ cementa! layer leads to a large increase in permeabil­ cium hydroxide treatment or short-term barriers (eg, ity. Bacterial toxins are free to pass through the den­ mineral trioxide aggregate and collagen plugs) may tinal tubules and stimulate an inflammatory response also be used to ensure a better prognosis for non­ in the corresponding periodontal ligament.125 The surgical endodontic therapy122·123 (see Fig 17-10). If result is resorption of the root and bone. nonsurgical therapy has been unsuccessful in arrest­ The periodontal infiltrate consists of granulation ing the resorption, apical surgery should be attempt­ tissue with lymphocytes, plasma cells, and polymor­ ed, provided that a sufficient crown-root ratio will be phonuclear leukocytes. Multinucleated giant cells present after the surgery. may bind to exposed RGD peptides and resorb The second type of external root resorption the denuded root surface. This process continues caused by pulp space infection is lateral external until the stimulus (microbes within the pulp space) is inflammatory resorption. Lateral periodontitis with removed (Fig 17-12). Radiographically, the resorption external root resorption may result when the root is observed as progressive radiolucent areas of the loses its cementa I protection (Fig 17-11 ). For pulp root and adjacent bone (see Fig 17-11 ). space infection to develop, the pulp must first The treatment protocol for external root resorp­ become necrotic. Necrosis occurs after a serious tion caused by pulp space infection is to first rec­ injury in which displacement of the tooth results in ognize the attachment damage resulting from severing or compression of the apical blood vessels. the traumatic injury and minimize the subsequent In mature teeth, the dental pulp has little regen­ inflammation. The clinician should ideally evaluate eration potential, and the necrotic pulp will usually pulp space infection 7 to 10 days after the injury.86·87 become infected within 3 weeks. The microbial profile Disinfection of the root canal systems removes the of a traumatized necrotic pulp should resemble that stimulus to the periradicular inflammation, and the of a primary endodontic infection with upward of 107 resorption will stop. In most cases, a new attachment

406 www.shayanNemodar.com ExternalRoot Resorption

will form; however, if a large area of root is affected, osseous replacement may result by the mechanism already described. The two major treatment principles are prevention of pulp space infection and elimination of any bacte­ ria present in the pulp space. An effective way to pre­ vent pulp space infection is, of course, to maintain the vitality of the pulp. If the pulp remains vital, the canal will be free of bacteria, and thus this type of external inflammatory root resorption will not occur. Fig 17-13 Cross section of a root filled with calcium hydroxide. The pH After severe injuries where vitality has been lost, indicator shows that the canal and surrounding dentin are basic, while the sur­ rounding tissue is slightly acidic. it is possible under some circumstances to promote revascularization of the pulp. Such revascularization is possible in young teeth with incompletely formed apices if the teeth are replaced in their original posi­ tion within 60 minutes of the injury.126 If the tooth has been avulsed, soaking it in doxycycline for 5 minutes so soon after a serious traumatic injury; therefore, before reimplantation has been shown to double the it is beneficial to start the endodontic treatment revascularization rate. However, even under the best with chemomechanical preparation, after which an conditions, revascularization will occur only about intracanal dressing of creamy calcium hydroxide is 50% of the time, which poses a diagnostic dilemma. placed.129 The practitioner can then obturate the If the pulp revascularizes, external root resorption will canal when periodontal healing of the injury is com­ not occur and the root will continue to develop and plete, approximately 1 month after the instrumenta­ strengthen. However, if the pulp becomes necrotic tion visit. There appears to be no need for long-term and infected, the subsequent external inflammatory calcium hydroxide treatment in cases where endo­ root resorption that develops could result in the loss dontic treatment is started within 10 days of the of the tooth in a very short time. injury. However, calcium hydroxide can be applied At present, the diagnostic tools available cannot in a compliant patient for up to 6 months to ensure detect a vital pulp in this situation until approximate­ periodontal health prior to root canal filling with ly 6 months following successful revascularization. gutta-percha. This period of time is unacceptable because by that When root canal treatment is initiated later than time the teeth that have not revascularized would be 10 days after the accident or when active extern a I lost to the resorptive process. Recently, however, the inflammatory resorption is observed, the preferred laser Doppler flowmeter has been shown to be an antibacterial protocol consists of chemomechan­ excellent diagnostic tool for the detection of revas­ ical preparation followed by long-term dressing cularization in immature teeth. This device appears with densely packed calcium hydroxide. The latter to accurately detect the presence of vital tissue creates an alkaline pH in the surrounding dentinal in the pulp space by 4 weeks after the traumatic tubules (Fig 17-13), kills bacteria, and neutralizes injury.121 endotoxin, a potent inflammatory stimulator.130 The second major treatment principle is the elim­ The patient's first visit consists of thorough che­ ination of any microbes present in the pulp space. momechanical instrumentation of the root canal Revascularization cannot occur in teeth with closed systems and placement of a creamy mix of calcium apices. These teeth must be endodontically treat­ hydroxide and an intracanal antibacterial agent with ed before the ischemically necrotic pulp becomes a lentulo instrument. The patient is then seen in infected, that is, within 7 to 10 days of the injury.128 approximately 1 month, at which time the canal sys­ From a theoretic point of view, timely treatment tems are filled with a dense mix of calcium hydrox­ of these teeth may be considered equivalent to the ide. Once filled, the canals appear radiographically treatment of teeth with vital pulp. Therefore, endo­ to be calcified because the radiodensity of calcium dontic treatment may be completed in one visit. hydroxide in the canal is usually similar to that of the However, efficient treatment is extremely difficult surrounding dentin.

407 www.shayanNemodar.com Root Resorption

origin occurs immediately below the epithelial attach­ ment of the tooth, usually (but not exclusively) at the cervical area of the tooth. Because of this location, it has been referred to as subepithelial inflammatory root resorption. Although this process is often called cervical root resorption, the perio-dontal attachment of teeth is not always at the cervical margin; the same process can occur more apically on the root surface. In fact, the anatomical connotation of "cervical" root resorption has led to confusion and misdiagnosis of this condition, inspiring attempts to rename this type of external resorption.89·131-133 The pathogenesis of subepithelial inflammatory Fig 17-14 Tooth treated for external inflammatory resorption with long-term root resorption is not fully understood.89 However, calcium hydroxide medication. (a) At the start of treatment, radiolucencies are present in the root and adjacent bone, indicating active resorption. (b) At the because its histologic appearance and progressive 9-month follow-up, the radiolucencies have disappeared on the adjacent bone, nature are identical to other forms of progressive and a lamina dura has re-formed, indicating that the process has stopped. (c) inflammatory root resorption, it seems logical that The canal is obturated with gutta-percha and sealer. the pathogenesis would be the same (ie, an unpro­ tected or altered root surface that attracts resorbing cells and an inflammatory response maintained by infection). Other theories propose that the process could be a type of benign proliferative fibrovascular or fibro-osseous disorder in which bacteria are only involved secondarily. Additional radiographs are taken at 3-month Although an exact etiology has not been identi­ intervals. At each visit, the tooth is tested for symp­ fied, several predisposing factors have been associ­ toms of periodontitis. In addition to tracking the ated with subepithelial inflammatory root resorption. resorptive process, the clinician should assess the These include trauma, orthodontics, intracoronal presence or absence of the calcium hydroxide (ie, bleaching, dentoalveolar surgery, and periodontal calcium hydroxide washout). Because the root sur­ disease or treatment. The dental pulp does not face is so radiodense as to make the assessment appear to play a direct role and is usually normal in of healing difficult, healing of the adjacent bone these cases, unless exposure results from the resorp­ is also assessed. If the adjacent bone has healed, tive process.132 Because the source of stimulation the resorptive process can be presumed to have (infection) is not the pulp, it has been postulated stopped in the root as well, and the canal systems that bacteria in the sulcus of the tooth stimulate and may be obturated with gutta-percha (Fig 17-14). sustain an inflammatory response in the periodon­ If the practitioner believes that additional healing tium at the attachment level of the root.134 before obturation would be beneficial, the condi­ Subepithelial inflammatory root resorption is tion of the calcium hydroxide in the canal should be asymptomatic and is usually detected only through assessed. If the canal still appears radiographically routine radiographs. Occasionally, symptoms of pul­ to be calcified, there is no need to replace the cal­ pitis will develop if the resorption is extensive. When cium hydroxide. If, on the other hand, the canal has the resorption is long-standing, granulation tissue regained its radiolucent appearance, then the cal­ may undermine the enamel of the crown of the tooth, cium hydroxide should be repacked and reassessed resulting in a pinkish appearance. This "pink spot" in another 3 months.86,87 has traditionally been used to describe the pathog­ nomonic clinical picture of internal root resorption, Sulcular infection leading to the misdiagnosis and treatment of many Sulcular infection represents another inflammatory cases of subepithelial inflammatory root resorption as stimulus that can cause external root resorption. This internal root resorption (Fig 17-15). progressive external root resorption of inflammatory

408 www.shayanNemodar.com External Root Resorption

Fig 17-15 (a) Pink spot of external inflammatory resorption. The granulomatous tissue has spread coronally Fig 17-16 Radiographic appearance of exter­ and undermined the enamel, causing the pink color in the crown. (b) Careful removal of the granulomatous tis­ nal subepithelial root resorption. The resorptive sue shows the canal to be almost entirely encircled but not penetrated by the resorptive defect. (Courtesy of Dr defect on the mesial side of the molar shows Henry Rankow, Harrisburg, PA.) a small opening into the root. The apical and coronal expansion reaches but does not pen­ etrate the pulp canal. Note the adjacent bone resorption.

Fig 17-17 (a) Radiographic appearance of a maxillary incisor with external root resorption extending coronally. Note the outline of the root canal through the resorptive radiolucency. (b) The clinical appearance shows a pink spot close to the gingival margin on the labial surface of the tooth.

The radiographic appearance of subepithelial utilized to allow better judgment of the location and 7 inflammatory root resorption can be quite variable. extent of invasive cervical root resorption.13>-13 If the resorptive process occurs mesially or distally A useful classification scheme has been pro­ on the root surface, small radiolucent openings into posed for the evaluation of and treatment plan­ the root are common. The radiolucency expands ning for subepithelial inflammatory root resorption coronally and apically in the dentin and reaches, but lesionsB9 (Fig 17-18). It is based on the extent of inva­ usually does not perforate, the root canal (Fig 17-16). sion and has been correlated with outcomes in one If the resorptive process is buccal or palatolingual, clinical study.BB the radiographic picture is dependent on the extent Treatment modalities rely on the removal of the to which the resorptive process has spread in the resorptive tissue and restoration of the defect with a dentin. It is seen as a radiolucency at the attachment suitable material. The outcome of treatment appears level or as mottled if it has spread coronally or api­ to be directly related to the extent of the resorptive cally to any considerable degree. Because the pulp is process at the time of intervention. Therefore, early not involved, its outline can usually be distinguished intervention improves the prognosis. Space limita­ through the resorptive defect (Fig 17-17). Cone beam tions preclude a complete review of the treatment computed tomographic (CBCD technology has been strategies for subepithelial inflammatory root resorp-

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Fig 17-18 Clinical classification of invasive cervical resorption. Class 1: small, invasive resorptive lesion near the cervical area with shallow penetration into dentin. Class 2: well-defined, invasive resorptive lesion that has penetrated close to the coronal pulp chamber but with little or no extension into the root dentin. Class 3: deeper invasion of the root dentin by resorbing tissues that extend into the coronal third of the root. Class 4: large, invasive resorptive process that has extended beyond the coronal third of the root. (Reprinted from Heithersay138 with permission.)

Class 1 Class 2 Class 3 Class 4

tion. Recent reviews discuss strategies for treating invasive cervical resorption (subepithelial inflamma­ 9 this form of external root resorption.133·13 tory root resorption, discussed previously) was attrib­ uted to intracoronal bleaching.88 Bleaching To date, the exact mechanism for the sporadic lntracoronal bleaching of discolored endodonti­ occurrence of cervical root resorption after intracor­ cally treated teeth (ie, the walking bleaching tech­ onal bleaching of endodontically treated teeth has nique) has been cited as a cause of external resorp­ not been fully elucidated. It appears that a history tion.140-143 Case reports published between 1979 of traumatic injury, the application of heat, and the and 1991 indicated that cervical resorption of endo­ acidity of the external root environment adjacent to dontically treated teeth was mostly associated with the application of the bleaching agent all contribute trauma and the use of hydrogen peroxide as the to the resorption phenomenon. Resorption does not sole intracoronal bleaching agent or with the use of occur immediately but appears a few years after the sodium perborate as an adjunctive bleaching agent. bleaching procedure. Thus, follow-up of intracoro­ Root resorption was considerably more severe when nally bleached teeth is mandatory. Manifestations the oxidizing effect of hydrogen peroxide was cata­ of cervical resorption could be caused by bacte­ lyzed by the use of a heat source. rial penetration into dentinal tubules after traumatic Four major follow-up studies between 1988 damage to the cementum. Also, increased dentin and 1998 examined the occurrence of cervical root permeability associated with the use of hydrogen resorption in endodontically treated teeth that had peroxide has been surmised as a predisposing factor undergone intracoronal bleaching from 1 to 15 in the initiation of such a resorptive process. years. Of the 58 teeth that were bleached using 30% A patient who requests tooth whitening of endo­ hydrogen peroxide and heat, approximately 7% (ie, dontically treated teeth should be duly informed four patients) exhibited evidence of cervical root of the potential consequence of cervical resorption resorption after 1 to 8 years.144 Another follow-up before such a procedure is administered. In view study that involved the recall of 95 teeth that had of the potential complications associated with the histories of traumatic injury over a period of 3 years use of hydrogen peroxide and occasionally sodium did not reveal any evidence of cervical root resorp­ perborate as intracoronal bleaching agents, 10% tion with the use of sodium perborate in water.145 to 37% carbamide peroxide has been suggested Similarly, two other follow-up studies, in which as an alternative intracoronal bleaching agent.148-150 the walking bleaching technique had been used Although carbamide peroxide has been shown to be to bleach nontraumatically involved, tetracycline­ as effective as sodium perborate for lightening tooth stained, endodontically treated teeth with sodium color under in vitro conditions, there are no clinical perborate and oxygen-water146 or sodium perborate data available on its efficacy in bleaching discolored with 30% hydrogen peroxide147 did not reveal any endodontically treated teeth. sign of cervical resorption. Approximately 4% of

410 www.shayanNemodar.com Internal InflammatoryRoot Resorption

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... ,

Fig 17-19 Histologic sections of internal root. (a) Bacteria are seen in the den­ tinal tubules communicating between the necrotic coronal segment and the apical granulation tissue and resorbing cells. (b) Apical dentin is resorbed (Brown & Brenn a b stain; original magnification x 100). (Courtesy of Dr Leif Tronstad, Oslo, Norway.)

Internal Inflammatory Root tions necessary for recruitment and activation of the elastic cells that mediate resorption. Resorption There are different hypotheses on the origin of the pulpal granulation tissue involved in inter­ nal resorption. The first and most widely accepted Internal inflammatory root resorption occurs in re­ hypothesis is that infected coronal pulp tissue leads sponse to infection and in general responds favor­ to the formation of adjacent apical granulation pulp ably to conventional treatment. It is classified, based tissue (see chapter 10). A second hypothesis pro­ on location, as apical or intraradicular. Apical internal poses that the granulation tissue is of nonpulpal inflammatory root resorption has been shown to origin, possibly originating from cells circulating in be a common occurrence in teeth with periapical the vascular compartment or from cells originating pathosis.151 The majority of teeth with periapical in the periodontium. It has been shown that com­ pathosis demonstrate some degree of apical internal munication between the coronal necrotic tissue and resorption when analyzed with scanning electron the vital pulp is through appropriately oriented den­ microscopy. These lesions may not be apparent clini­ tinal tubules 152 (see Fig 17-19a). One investigation cally; nevertheless, the clinician should presuppose reported that resorption of the dentin is frequently their presence. Apical internal inflammatory resorp­ associated with deposition of hard tissue resembling tive lesions most likely contribute to the observed bone or cementum, not dentin.126 The investigators inaccuracies of electronic length determination in postulated that the resorbing tissue is not of pulpal teeth with large apical lesions. lntraradicular internal origin but is actually "metaplastic" tissue derived resorption is identified as a round or oval lesion con­ from pulpal invasion by macrophage-like cells cir­ tained within the root canal. culating in the vascular compartment. Still others Conventional endodontic therapy will stop pro­ have proposed that the pulp tissue is replaced by gression of the lesion. Early intervention can prevent periodontium-like connective tissue when internal perforation of the periodontium, which can compli­ resorption is present.153 These hypotheses are not cate clinical management. mutually exclusive, and it is possible that all contrib­ ute to the formation of granulation tissue in pulp in various clinical cases. Etiology In addition to the presence of granulation tissue in pulp, internal root resorption takes place only Internal root resorption is marked by resorption of when the odontoblastic layer and predentin are lost the internal aspect of the root via multinucleated or altered.132 Causes of predentin loss adjacent to giant cells adjacent to granulation tissue in the pulp granulation tissue are not obvious, but trauma has (Fig 17-19). Chronic inflammatory tissue is common been frequently suggested, 154 perhaps even as an in the pulp, but only rarely does it result in the condi- initiating factor in internal resorption.153 Traumatic

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Fig 17-21 Incisor with internal root Fig 17-20 Mandibular central incisor with a pink spot indicating internal resorption. Uniform enlargement of the root resorption. The pink discoloration is due to the undermining of the enamel pulp space is apparent. The outline of the by granulomatous tissue. Because the pink spot is so far from the periodontal canal is not visible in the resorptive defect. attachment level, this example is unlikely to be external in nature. Adjacent bone is intact.

episodes are divided into two types: transient and Traditionally, the pink tooth, resulting from the progressive, the latter of which requires continuous granulation tissue in the coronal dentin that under­ stimulation by infection. mines the coronal enamel, has been thought to Another possible cause of predentin loss may be be pathognomonic of internal root resorption (Fig extreme heat produced by cutting of dentin without 17-20). However, as already discussed, a pink tooth an adequate water spray (see chapters 14 and 15). can also be a feature of subepithelial external inflam­ The heat presumably destroys the predentin layer, matory root resorption, which must be ruled out predisposing the tooth to internal resorption if there before a diagnosis of internal root resorption is made. is continued inflammatory stimulation of the coronal pulp. Under these conditions, bacteria and their by­ products initiate inflammation, thereby stimulating Radiographic appearance resorbing giant cells in the vital pulp adjacent to the denuded root surface. In support of this possible The usual radiographic presentation of internal root scenario, internal root resorption has been produced resorption is a fairly uniform radiolucent enlarge­ experimentally by the application of diathermy.155 ment of the pulp canal (Fig 17-21). Because the resorption is initiated in the root canal, the resorp­ tive defect includes some part of the root canal Clinical manifestations space. Therefore, the original outline of the root canal is distorted. Only on rare occasions when the Internal root resorption is usually asymptomatic and internal resorptive defect penetrates the root and is first recognized clinically through routine radio­ impacts the periodontal ligament does the adja­ graphs. Pain may be a presenting symptom if perfo­ cent bone show radiographic changes. Angled con­ ration of the crown occurs and the granulation tissue ventional radiographs (Fig 17-22) as well as newer is exposed to oral fluids. For internal resorption to three-dimensional imaging methods can help to be active, at least part of the pulp must be vital so discriminate between internal and external resorp­ that a positive response to pulpal sensitivity testing tive processes. is possible. The coronal portion of the pulp is often necrotic, whereas the apical pulp, which includes the internal resorptive defect, may remain vital. There­ Histologic appearance fore, a negative sensitivity test result does not rule out active internal resorption. It is also possible that Like that of other inflammatory resorptive defects, the pulp will become nonvital after a period of active the histologic presentation of internal resorption is resorption, resulting in a negative sensitivity test, granulation tissue with multinucleated giant cells. An radiographic signs of internal resorption, and radio­ area of necrotic pulp is present coronal to the granu­ graphic signs of apical inflammation. lation tissue. Dentinal tubules that contain micro-

412 www.shayanNemodar.com Diagnostic Features of External and Internal Root Resorption

Fig 17-22 (a and b) Difference between appearances of external (a) and internal (b) root resorption when the radiographic angle is changed. (Courtesy of Dr Claudia External resorption Internal resorption a b Barthel, Dusseldorf, Germany.)

organisms and communicate between the necrotic Diagnostic Features of External zone and the granulation tissue are sometimes vis­ ible (see Fig 17-19a). Unlike the bone in external and Internal Root Resorption root resorption, the adjacent bone is not affected by internal root resorption. It is often very difficult to distinguish external from internal root resorption, so misdiagnosis and incor­ Treatment rect treatment can result. This section discusses typi­ cal diagnostic features of each type of resorption. Tr eatment of internal root resorption is conceptually Box 17-1 provides an overview of the key elements very easy. Because the resorptive defect is the result of these diagnostic features and may serve as a of the inflamed pulp and the blood supply to the tis­ quick reference for clinical practice. sue is through the apical foramina, endodontic treat­ ment that effectively removes the blood supply to the resorbing cells is the treatment approach. After Radiographic features adequate anesthesia is obtained, the canal apical to the internal defect is explored and a working length A change of x-ray angle should give a fairly good determined. The apical canal is thoroughly instru­ indication of whether a resorptive defect is internal mented to ensure that the blood supply to the tissue or external. A lesion of internal origin appears close resorbing the root is eliminated. to the canal whatever the angle of the x-ray (Figs When the root canal instrumentation is com­ 17-22 and 17-23). On the other hand, a defect on pleted, paper points should be able to maintain a the external aspect of the root seems to move away blood-free, dry canal. Calcium hydroxide is admin­ from the canal as the x-ray angle changes (Figs 17-22 istered to the canal to facilitate removal of the tis­ and 17-24). In addition, it is usually possible to dis­ sue in the irregular defect at a subsequent visit, tinguish whether the external root defect is buccal when the tooth and defect are sealed. Ultrasonic or palatolingual by using the buccal object rule. In instrumentation and irrigation may also be of help in internal resorption, the outline of the root canal is removing tissue in irregularities and undercuts that usually distorted, and the root canal and the radio­ conventional instrumentation cannot remove. Barrier lucent resorptive defect appear contiguous. When techniques utilizing mineral trioxide aggregate may the defect is external, the root canal outline appears be necessary in large apical resorptive defects.156 normal and can usually be seen "running through" the radiolucent defect (see Fig 17-21). Although intraoral radiography provides an acceptable level of accuracy in the diagnosis of

413 www.shayanNemodar.com Root Resorption ' ox 17_1 Typical ?iagnostic features of root B resorption Apical external inflammatory root resorption due to pulpal infection

• Negative pulpal sensitivity test, with or without a history of trauma

Lateral external inflammatory root resorption due to pulpal infection

• History of trauma • Negative pulpal sensitivity test • Lesion repositioned on angled radiographs • Root canal visible radiographically overlying the defect • Apparent bony radiolucency Fig 17-23 Internal resorption. Radiographs from two different hori­ (a and b) zontal projections depict the lesion within the confines of the root canal. Subepithelial external inflammatory root resorption due to sulcular infection

• History of trauma (often forgotten or not understood by the patient) • Positive pulpal sensitivity test • Lesion at the attachment level of the tooth • Lesion repositioned on angled radiographs • Undistorted and radiographically visible root canal outline • Crestal bony defect associated with the lesion • Pink spot possible

Internal root resorption

• History of trauma, crown preparation, or pulpotomy • Positive pulpal sensitivity test likely • Lesion at any location along the root canal (not only at attachment level) • Lesion associated with the root canal on angled radiographs a • Radiolucency contained in the root without an adjacent Fig 17-24 External resorption. Radiographs from two different bony defect (a and b) horizontal projections depict movement of the lesion to outside the confines of • Pink spot possible the root canal. root resorption, the use of CBCT enables three­ occasions, if the internal defect perforates the root, dimensional imaging of root resorption defects from the adjacent bone is resorbed and appears radiolu­ the coronal, sagittal, and axial aspects (Fig 17-25). In cent on the radiograph. addition, the associated use of volumetric construc­ tion enhances visualization of the portals of entrance in the case of external resorption and also the loca­ Vitality testing tion and extent of the resorption defect as well as the degree of osseous involvement13>-137 (Fig 17-26). External inflammatory resorption on the apical and Improvements in diagnostic accuracy with the use lateral aspects of the root involves an infected pulp of CBCT also increase the likelihood of correct man­ space, indicated by a negative response to sensitiv­ agement of resorptive lesions.157 ity tests. On the other hand, because subepithelial External inflammatory root resorption is always external root resorption does not involve the pulp accompanied by resorption of the bone in addition (the bacteria are thought to originate in the sulcus to the root (see Figs 17-11and 17-16). Therefore, of the tooth), this type of resorption is often associ­ radiolucencies are apparent in the root as well as ated with a normal response to sensitivity testing. the adjacent bone. Internal root resorption does not Internal root resorption usually occurs in teeth with involve the bone; as a rule, the radiolucency is con­ vital pulps and elicits a positive response to sensitiv­ fined to the root (see Figs 17-21and 17-3)2 . On rare ity testing. However, teeth that exhibit internal root

414 www.shayanNemodar.com Systemic Causes of Root Resorption

Fig 17-26 Proximal volu­ metric reconstruction shows the presence of root resorp­ Fig 17-25 (a) Periapical view of the mandibular tion on the facial surface right central incisor showing subepithelial external of a mandibular right cen­ resorption. (b) Axial cut from a volumetric recon­ tral incisor. (Reprinted from struction shows the location, extent, and proximity Cohenca et al135 with per­ of external resorption to the root canal. (Reprinted mission.) from Cohenca et al135 with permission.)

resorption sometimes register a negative response external resorption should be initiated. Also, upon to sensitivity testing, often in cases where the cor­ obturation in cases of internal resorption, it should onal pulp is removed or necrotic and the active be possible to fill the entire canal from within. Failure resorbing cells are located more apical in the canal. to fill the canal suggests an external lesion. Finally, if In addition, the pulp may become necrotic after the blood supply of an internal resorption defect is active resorption has taken place. removed upon pulp extirpation, any continuation of the resorptive process on recall radiographs should alert the dentist to the possibility that an external Pink spot resorptive defect was misdiagnosed.

Because the pulp is nonvital in both apical and lateral external root resorption, the granulation tis­ sue that produces a pink spot is not present in such Systemic Causes of Root cases. However, a pink spot caused by granulation tissue that undermines enamel is a possible sign of Resorption both subepithelial external root resorption (see Fig 17-15) and internal root resorption (see Fig 17-20). The roots of teeth show a remarkable resistance to detectable resorption, even with systemic diseases Common misdiagnoses that can cause significant bone resorption (see chap­ ter 20). With hyperparathyroidism osteitis deformans The majority of misdiagnoses of resorptive defects (Paget disease), for example, radiographically appar­ are made in distinguishing between subepithelial ent bone resorption is not accompanied by resorp­ external root resorption and internal root resorp­ tion of the roots.158 However, hormonal disturbances tion. A diagnosis should always be confirmed while and genetic factors have been shown sometimes to treatment is proceeding. When root canal therapy is cause resorption of the roots.96.107.159 the treatment of choice for an apparent internal root The preponderance of research on the genetic resorption that has not perforated the periodontium, propensity to develop root resorption has been con­ bleeding within the canal should cease quickly after ducted on populations of orthodontic patients. An pulp extirpation if the blood supply to the granula­ IL-1 f3 polymorphism has been positively correlated tion tissue is the apical blood vessels. However, if with an increased risk for external apical root resorp­ bleeding continues during treatment, particularly tion secondary to orthodontic tooth movement. if it is still present at the second visit, the source Individuals homozygous for the IL1B (+3953) allele 1 of the blood supply is external and treatment for have a 5.6-fold greater risk of root resorption greater

415 www.shayanNemodar.com Root Resorption

than 2 mm than do control populations.110•111 Wheth­ 20. Chen YH, Chang HH, Chen YJ, Lee D, Chiang HH, Yao CC. Root contact dur­ ing insertion of miniscrews for orthodontic anchorage increases the failure er this same genetic variation plays a role in other rate: An animal study. Clin Oral Implants Res 2008; 19:99-106. types of dental resorption is not presently known. 21. Hembree M, Buschang PH, Carrillo R, Spears R, Rossouw PE. Effects of Renal dystrophy results in an increased oxylate intentional damage of the roots and surrounding structures with miniscrew implants. Am J Orthod Dentofacial Orthop 2009; 135:280.e1-280.e9. concentration in the blood and precipitation in the 22. Hatakeyama J, Philp D, Hatakeyama Y, et al. Amelogenin-mediated regula­ hard tissues, which can cause root resorption.160•161 tion of osteoclastogenesis, and periodontal cell proliferation and migration. Genetic linkage is implicated because idiopathic J Dent Res 2006;85:144-149. 23. Yagi Y, Suda N, Yamakoshi Y, Baba 0, Moriyama K. In vivo application of external root resorption has been observed in mem­ amelogenin suppresses root resorption. J Dent Res 2009;88: 176-181. bers of the same family.107 As knowledge and test 24. Kong YY, Yoshida H, Sarosi I, et al. OPGL is a key regulator of osteoclasto­ genesis, lymphocyte development and lymph-node organogenesis. Nature procedures advance, resorption presently diagnosed 1999;397:315-323. as idiopathic will probably be increasingly found to 25. Khosla S. Minireview: The OPG/RANKL/RANK system. Endocrinology be of systemic or genetic origin. 2001; 142:5050-5055. 26. Tyrovola JB, Spyropoulos MN, Makou M, Perrea D. Root resorption and the OPG/RANKURANK system: A mini review. J Oral Sci 2008;50:367-376. 27. Boyce BF, Xing L. Functions of RANKURANK/OPG in bone modeling and remodeling. Arch Biochem Biophys 2008;473:139-146. I References 28. Wright HL, McCarthy HS, Middleton J, Marshall MJ. 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Inheritance of susceptibility to root resorption associated with imaging in dento-alveolar trauma. Part 2: Root resorption. Dent Traumatol orthodontic force in mice. Am J Orthod Dentofacial Orthop 2008; 134: 2007;23:105-113. 742-750. 136. Patel S, Dawood A. The use of cone beam computed tomography in 110. Hartsfield JK Jr. Pathways in external apical root resorption associated with the management of external cervical resorption lesions. Int Endod J orthodontia. Orthod Craniofac Res 2009;12:236-242. 2007;40:730-737. 111. Al-Qawasmi RA, Hartsfield JK Jr, Everett ET, et al. Genetic predisposi­ 137. Patel S, Dawood A, Wilson R, Horner K, Mannocci F. The detection and tion to external apical root resorption. Am J Orthod Dentofacial Orthop management of root resorption lesions using intraoral radiography and 2003;1 23:242-252. cone beam computed tomography-An in vivo investigation. Int Endod J 112. Al-Qawasmi RA, Hartsfield JK Jr, Everett ET, et al. Genetic predisposition to 2009;42:831-838. external apical root resorption in orthodontic patients: Linkage of chromo­ 138. Heithersay GS. Invasive cervical resorption: An analysis of potential predis­ some-18 marker. J Dent Res 2003;82:356-360. posing factors. Quintessence Int 1999;30:83-95. 113. Luther F, Dominguez-Gonzalez S, Fayle SA. Teamwork in orthodontics: Lim­ 139. Heithersay GS. Management of tooth resorption. Aust Dent J 2007;52:­ iting the risks of root resorption. Br Dent J 2005;198:407-41 1. S 105-S 121. 114. Bhaskar SN. Periapical lesions: Types, incidence, and clinical features. Oral 140. Cahl JE, Pallesen U. Tooth bleaching -A critical review of the biological Surg Oral Med Oral Pathol Oral Radiol Endod 1966;21:657-671. aspects. Crit Rev Oral Biol Med 2003;14:292-304. 115. Lalonde ER, Luebke RG. The frequency and distribution of periapical cysts 141. Tredwin CJ, Naik S, Lewis NJ, Scully C. Hydrogen peroxide tooth-whitening and granulomas: An evaluation of 800 specimens. Oral Surg Oral Med Oral (bleaching) products: Review of adverse effects and safety issues. Br Dent J Pathol Oral Radiol Endod 1968;25:861-868. 2006; 200:371-376. 116. Dalton C, Phillips C, Pettiette M, Trope M. Bacterial reduction with nickel 142. Plotino G, Buono L, Grande NM, Pameijer CH, Somma F. Nonvital tooth titanium rotary instruments. J Endod 1998;24:763-777. bleaching: A review of the literature and clinical procedures. J Endod 117. Shuping GB, 0rstavik D, Sigurdsson A, Trope M. Reduction of intracanal 2008;34:394-407. bacteria using nickel-titanium rotary instrumentation and various medica­ 143. Goldberg M, Grootveld M, Lynch E. Undesirable and adverse effects of ments. J Endod 2000;26:751-755. tooth-whitening products: A review. Clin Oral lnvestig 201O;14:1 -10. 118. Bystrom A, Happonen R, Sjogren U, Sundqvist G. Healing of periapical 144. Friedman S, Rotstein I, Libfeld H, Stabholz A, Heling I. Incidence of external lesions of pulpless teeth after endodontic treatment with controlled asep­ root resorption and esthetic results in 58 bleached pulpless teeth. Endod sis. Endod Dent Traumatol 1987;3:58-63. Dent Traumatol 1988;4:23-26. 119. Sjogren U, Figdor D, Persson 5, Sundqvist G. Influence of infection at the 145. Holmstrup G, Palm AM, Lambjerg-Hansen H. Bleaching of discoloured root­ time of root filling on the outcome of endodontic treatment of teeth with filled teeth. Endod Dent Traumatol 1988;4:197-201. apical periodontitis. Int Endod J 1997;30:297-306. 146. Anitua E, Zabalegui B, Gil J, Gascon F. Internal bleaching of severe tet­ 120. Card S, Trope M, Sigurdsson A. 0rstavik D. The effectiveness of increased racycline discolorations: Four-year clinical evaluation. Quintessence Int apical enlargement in reducing intracanal bacteria. J Endod 2002;28: 1990;21 :783-788. 779-783.

418 www.shayanNemodar.com References

147. Abou-Rass M. Long-term prognosis of intentional endodontics and inter­ 154. Wedenberg C, Zetterqvist L. Internal resorption in human teeth: A histo­ nal bleaching of tetracycline-stained teeth. Compend Cantin Educ Dent logical, scanning electron microscope and enzyme histo-chemical study. J 1988; 19:1 034-1044. Ended 1987; 13:255-259. 148. Vachon C, Vanek P, Friedman S. Internal bleaching with 10% carbamide 155. Gottlieb B, Orban B. Veranderungen in Periodontium nach chirurgischer peroxide in vitro. Pract Periodontics Aesthet Dent 1998; 10:1145-1152. Diathermie. Z Stomatol 1930;28: 1208-1213. 149. Lim MY, Lum SO, Poh RS, Lee GP, Lim KC. An in vitro comparison of the 156. Camilleri J, Pitt Ford TR. Mineral trioxide aggregate: A review of the con­ bleaching efficacy of 35% carbamide peroxide with established intracoro­ stituents and biological properties of the material. Int Ended J 2006;39: nal bleaching agents. Int Ended J 2004;37:483-488. 747-754. 150. Carrasco-Guerisoli LD, Schiavoni RJ, Barroso JM, Guerisoli DM, Pecora JD, 157. Cotton TP, Geisler TM, Holden DT, Schwartz SA, Schindler WG. Endodontic Fr6ner IC. Effect of different bleaching systems on the ultrastructure of applications of cone-beam volumetric tomography. J Ended 2007;33: bovine dentin. Dent Traumatol 2009;25: 176-180. 1121-1132. 151. Vier FV, Figueiredo JA, Internal apical resorption and its correlation with 158. Smith BJ, Eveson JW. Paget's disease of bone with particular reference to the type of apical lesion. Int Ended J 2004;37:730-737. dentistry. J Oral Pathol 1981;10:223-247. 152. Wedenberg C, Lindskog S. Experimental internal resorption in monkey 159. Sharawy AM, Mills PB, Gibbons RJ. Multiple ankylosis occurring in rat teeth. Ended Dent Traumatol 1985;1:221-227. teeth. Oral Surg 1968;26:856-860. 153. Stanley HR. Diseases of the dental pulp. In: Tieck RW (ed). Oral Pathology. 160. Gold SI, Hasselgren G. Peripheral inflammatory root resorption: A review of New York: McGraw-Hill, 1965:95-130. the literature with case reports. J Clin Period onto I 1992; 19:523-534. 161. Moskow BS. Periodontal manifestations of hyperoxaluria and oxalosis. Periodontol 1989;60:271-278.

419 www.shayanNemodar.com www.shayanNemodar.com Aging and the Pulp

Harold E. Goodis, DDS

Arnold Kahn, PhD

Stephane Simon, DDS, MPhil, PhD

Advances in living standards, including medical care services increases with increasing age; clinical and dental care, have contributed to increased life findings suggest that individuals 65 years old or spans and a growing proportion of elderly people in older have more caries than young children,6·7 the population. The elderly often need more medi­ although the caries attacks cervical rather than cal and dental services compared to the average occlusal surfaces. Further, the number of teeth citizen, including root canal treatment.1 Results of with carious or restored root surfaces increases the a survey1 of Diplomates of the American Board of longer a person lives; more than half the retained Endodontists indicated that Diplomates examine teeth in individuals 75 years of age or older are patients covering a wide spectrum of ages but most affected.8 The changes occurring in the dental fall into the age range of 45 to 64 years. Respon­ pulp of elderly patients may explain the increase in dents indicated that about 26% of their patients are requests for endodontic treatment.9 This chapter at least 65 years old. A substantial majority (59%) of reviews age-dependent and age-independent

respondents (n = 334) indicated that the number of processes in the dental pulp and evaluates their patients aged 65 years or older is increasing in their impact on the quality of oral health care in the practices. elderly patient. The increased need for endodontic treatment among older individuals is due partly to naturally occurring anatomical and physiologic senescent changes that are associated with the aging process I Process of Aging and partly to diseases that occur more commonly in older adults2 (see chapter 20). Oral health is important because oral diseases affect more than A discussion of aging in a particular tissue or area the mouth.3 Normal aging processes in healthy of the body is based on biologic theories of replica­ individuals often have few adverse effects in the oral tive senescence, together with the roles of oxida­ cavity, but tooth loss, caries, periodontal diseases, tive stress and telomeres on the aging process. and pulpal and periradicular diseases will have Organismal senescence is the aging of whole organ­ deleterious consequences.4 isms. The term aging has commonly been equated The increased need for dental services for with senescence such that the terms can be used older individuals is also a reflection of the greater interchangeably. The role of telomeres, structures retention of teeth into old age.5 Utilization of dental found at the ends of chromosomes in the cells of

421 www.shayanNemodar.com Aging and the Pulp eukaryotes (single-celled or multicelled organisms Theories of senescence whose nucleus is surrounded by a membrane), is an important consideration in the aging process. Cel­ The process of senescence is complex, a mani­ lular senescence is the combination of processes of festation of many different mechanisms.19•20 Aging deterioration that follow the period of the develop­ involves genetic, molecular, cellular, systemic, and ment of an organism.10 organismal processes. However, despite being an Aging is generally characterized by the declining intensely active area of research, aging remains one ability of cells or organismal systems to respond of the most poorly understood of all biologic pro­ positively to stress.11 Therefore, the ultimate con­ cesses. This lack of understanding is mostly due to sequence of aging is death. There are differences the complexity of aging and its integrated nature in maximum life span between species, which as well as the difficulty of dissociating the effects correspond to differences in the "rate of aging." The of normal aging from those manifested as a conse­ inherited rate of aging makes a mouse elderly at 3 quence of age-associated disease conditions.19 years old and a human elderly at 90 years old. These Theories of senescence generally have been genetic differences affect the efficiency of DNA repair divided between the programmed and stochas­ and oxidative enzymes as well as the rates of free tic theories of aging. Programmed theories imply radical production. that aging is regulated by biologic clocks operat­ Evidence that cultured normal human and ing throughout human lifetimes. This regulation animal cells undergo a finite number of population depends on changes in gene expression that affect doublings in vitro has provided new insights into cellular maintenance, repair, and defense responses. age-related changes at the cellular level.12 The Stochastic theories purport that environmental con­ number of mitotic event.s that cultured, normal ditions impact living organisms, causing cumulative animal cells undergo seems to be inversely related damage to DNA, tissues, and cells by free radicals to the age of the donor.13·14 Limits on cell division and oxidative stress.17.20 and function also occur in vivo when normal cells Although the aforementioned theories still lin­ are transplanted serially; as cell doublings reach ger in recent literature, most gerontologists today their limit, hundreds of variables change from the believe that aging is a process of progressive fail­ molecular level to the whole cell, and many of these ure of homeodynamics of genes that maintain and changes are identical to those seen in intact humans repair, stochastic events that cause molecular dam­ and animals as they age.1s.16 age, and change events that determine the prob­ Aging can be distinguished from disease by ability of death. The interaction of maintenance and several differences. Aging occurs as a result of repair constitutes the homeodynamic dimension of either a purposeful program or random (stochastic) a biologic system, and aging can be considered a accidental events.17 Evidence indicates that genes reduction of homeodynamic space, mainly resulting do not drive the aging process but instead seem from increased heterogeneity. to be involved in the loss of molecular form and Evolutionary theory was advanced because of the function. The molecular fidelity of all molecules smaller probability that an organism will remain alive produced either before or after reproductive at an older age. The decreasing probability is due to maturity is the determinant of longevity, which is disease and accidents (random events not depen­ governed by the genome. Distinction between the dent on age). This results in a higher reproductive aging process and age-associated diseases is based rate at a young age and a shorter life span. This on the molecular definition of age. Unlike disease, theory has not been supported by research carried age changes occur in every multicellular animal that out in cell cultures. reaches a certain size when reproductively mature. Gene regulation has been identified using model Further, age changes cross all species barriers and organisms such as budding yeast, worms, or fruit occur in all members of a species only after the flies. Studies involving these organisms have demon­ age of reproductive maturation. Aging also occurs strated the presence of at least two conserved aging in all animals removed from the wild, occurring in pathways. Although gene expression is imperfectly all animated matter and having the same universal controlled, it is possible that random fluctuations in molecular etiology-that is, thermodynamic instab­ the expression levels of many genes contribute to ility. No disease shares these distinctions.18 aging.21

422 www.shayanNemodar.com Process of Aging

While senescence is not universal, evidence sug­ The cellular senescence theory of aging empha­ gests that cellular senescence evolved in certain sizes the importance of cellular signaling responses species as a mechanism to prevent cancer. In a few to damage. Accumulation of ROS in the cell modu­ simple species, senescence cannot be detected. lates various signals, resulting in accelerated mito­ These species have no postmitotic cells; they reduce genesis and premature cellular senescence.29 the effects of damaging free radicals by cell divi­ The molecular inflammatory theory of aging, sion that results in cytoplasmic dilution of noxious proposed more recently, stresses that activation of substances. Eventually they succumb to trauma or redox-sensitive transcriptional factors by age-related disease. oxidative damage induces the upregulation of proin­ The mitochondrial respiratory system is the major flammatory gene expression. Accumulation of ROS cellular source of reactive oxygen species (ROS) during aging might be responsible for aging-related and free radicals. Age-dependent imbalances in pathologic conditions such as cancer, arthritis, and the fraction of toxic by-products that may escape neurodegenerative diseases.30 the defense mechanisms of human cells can induce a broad spectrum of oxidative damage to the mol­ ecules in the mitochondria and the cells as a whole.22 Oxidative stress Accumulation of ROS inside of cells over time and as a function of cellular activity is a major deter­ Cellular senescence occurs when normal diploid dif­ minant of aging. Cellular damage caused by ROS ferentiated cells lose the ability to divide, a phenom­ impairs physiologic functions, increases the risk of enon now known as replicative senescence or the tissue disease, and reduces life span. The role that Hayflick phenomenon.12 In response to DNA dam­ ROS play in mitochondrial DNA (mtDNA) function age, cells with shortened telomeres either senesce and apoptosis in aging was reviewed by Lee and (age) or self-destruct (apoptosis) if repair cannot Wei.23 They suggested that enhanced oxidative occur. As noted earlier, senescence is not universal, stress, accumulation of mtDNA mutations, altered and senescence is not seen in single-cell organisms expression of a few clusters of mitochondrial genes, that reproduce through cellular mitosis. In some mitochondrial dysfunction, and apoptosis are major species (sponges, coral, lobsters), highly differenti­ contributors to human aging.24 ated cells become postmitotic and can no longer This oxidative stress theory of aging issued from replicate, thus experiencing replicative senescence. Harman's free radical theory,25 which postulates that Because human cellular senescence evolved as a production and accumulation of free radicals in aer­ way to prevent the onset and spread of cancers if obic organisms is an important determinant of cellu­ cell division continued, such cells accumulate DNA lar life span. To day, the oxidative stress theory is well mutations and therefore would be in increased dan­ accepted, but the direct cause-and-effect relation­ ger of developing disease. ship between the accumulation of oxidative damage Replicative senescence and oxidative stress, as and aging remains poorly understood.19 Oxidative discussed previously, play an important role in cel­ stress is defined as an excessive accumulation of lular aging of epithelial cells and increase the risk of ROS caused by an imbalance between production aging in several systems in humans.31-34 Oxidative and destruction of ROS, the latter by antioxidant stress causes a large increase (becoming less nega­ defenses. tive) in cellular oxidation reduction potential, or a Building further on the oxidative stress theory, large decrease in the reducing capacity of cellular new theories of aging have been advanced in recent redox couples such as glutathiones.35 The effects of years.26 The mitochondrial theory of aging hypothe­ oxidative stress depend on the size of these changes sizes that mitochondria play a key role in the control because cells are able to overcome small chang­ of aging: The production of ROS by electrons leav­ es and regain an optimal redox state. However, ing the electron transport chain can damage com­ more severe oxidative stress can cause cell death ponents of the electron transport chain itself as well via apoptosis in moderate oxidation36; more intense as mtDNA, leading to a reduction of mitochondrial stresses cause cell necrosis. function.27 The evidence of increasing mtDNA dam­ A particularly destructive aspect of oxidative age with age may support this theory.28 stress is the production of ROS, which include free

423 www.shayanNemodar.com Aging and the Pulp

radicals and peroxides. Some less reactive species cells are not effectively controlled, the detrimental (superoxide) are converted by oxide-reduction reac­ effects of oxidative stress can accumulate.31·40.42 Mito­ tions or other redoxcycling compounds (quinines) chondrial dysfunction in cells leads to replicative into more aggressive species that cause extensive senescence, where the irreversible loss of division cellular damage.37 Most of these oxygen-derived potential of somatic cells occurs after a more or less species are produced at a low level by aerobic constant number of cell divisions.42 metabolism, and the cellular damage caused is con­ stantly repaired. However, under severe levels of oxidative stress that cause necrosis, the resulting Telomeres damage causes adenosine triphosphate depletion, preventing controlled apoptotic death and resulting Te lomeres have an important role in replicative in increased membrane permeability, loss of cellular senescence. Te lomeres are extensions of the linear, enzymes, and osmotic lysis.37 double-stranded DNA molecules that compose One of the most widely accepted theories of chromosomes. They are located at each end of both aging concerns the idea that oxygen-derived free chromosomal strands. Therefore, 1 chromosome radicals cause age-related impairment through oxi­ will have 4 telomeric tips, and the 46 chromosomes dation to biomolecules, and mitochondria are the found in human cells have 92 telomeric ends. In main target of this free radical attack.38 Many meta­ 1960, it was found that cells have a built-in counting bolic and physiologic processes need oxygen radi­ mechanism that limits their capacity to replicate (the cals, so an equilibrium between their production and Hayflick limit).11 The only cells capable of continued their antioxidant-linked inactivation is required to division appear to be cancer cells. This suggests that preserve health. Thus, senescence is the result of an normal cells do not have the potential to divide and imbalance between free radical production and anti­ function indefinitely. oxidant defenses. This process is evident in immune Hayflick and Moorhead11 suggested that the lim­ cells, which use free radicals in their protective func­ ited capacity of normal cells to divide is an expres­ tions, resulting in a senescent deterioration linked to sion of aging, leading to the determination of the oxygen stress.38 longevity of the organism. Therefore, cells require a The most direct test of the free radical-oxidative mechanism, located in the cell nucleus, to count the stress theory is to specifically alter the age-related number of times cellular replication occurs. A group increase in oxidative damage and determine how this of researchers at the University of California43A4 alteration affects aging. New investigations in the use found that telomeres in cultured fibroblasts shorten of genetically altered laboratory animals test the role each time a cell divides. At a certain shorter length, of oxidative damage in aging.39 In mammalian model telomeres signal a cell to stop dividing, indicating systems, evidence of oxidative stress effects indicates that cellular aging is not based on the passage of that antioxidant treatment protects against age-related time but on the telomeric measurement of rounds of dysfunction. Linkage between aging and oxidative DNA replication (Fig 18-1). stress is believed to occur because ROS generated Von Zglinicki45 showed that replicative senes­ under various conditions are able to oxidize nucleic cence is tied to organismal aging processes and acids, proteins, and lipids, and aging is associated that telomeres appear to be a major trigger. He with the accumulation of oxidized forms of cellular developed a model of telomere shortening and constituents.40 The accumulation of oxidative damage signaling by determining telomere structure, func­ is one of the most widely accepted causes of aging. tion of telomere-binding proteins, and sensitivity of Mitochondrial dysfunction, in particular damage to telomeres to oxidative damage. He later suggested mtDNA, appears to be responsible for increased that oxidative stress is an important modulator of production of ROS, thus acting as a causal factor for telomere loss, leading to telomere-driven replica­ aging.41 tive senescense.46 Additional details are available in Mitochondria are a cell's single greatest source articles on the physiology and pathophysiology of of both adenosine triphosphate and ROS. ROS are aging.18.47-so important for many life-sustaining processes of cells Others have found that shortening of telomeres and tissues, but they can also induce cell dam­ in immortal eukaryotic cells (cells with a nucleus that age and death. If their production and levels within contains the cell's chromosomes and that are larger

424 www.shayanNemodar.com Age-Related Changes in the Pulp

5' 3' I Age-Related Changes in the Pulp

Numerous changes in the dental pulp occur as a con­ sequence of the aging process. These changes have been observed in animal experiments and human studies through examination of extirpated dental pulp tissue or tissue harvested from extracted teeth, especially third molars. Age-related changes have been viewed as either functional, occurring through use (ie, "wear and tear"), or geriatric (ie, due to fac­ tors intrinsic to the normal aging process)M·65 Fig 18-1 Telomere shortening. Telomeres shorten because of the leading­ strand phenomenon that is exhibited during DNA replication in eukaryotes only. Characteristic changes with aging in fully formed Because DNA replication does not begin at either end of the DNA strand but human teeth were first described by Lacasagne in starts in the center, and because all DNA polymerases that have been discovered 1889 (cited by Johanson66) and scientifically con­ move in the 5' to 3' direction, the DNA molecule being replicated contains a firmed in 1950.67 In human teeth, aging alters the leading strand and a lagging strand. cell density of the pulp tissue and the dentinogenic activity of the surviving odontoblasts, leading to an increase in dentinal thickness and progressive reduc­ tion of space in the pulp canal and pulp chamber. In general, the number of cells in the pulp diminishes with age; proliferative activity peaks early in life. However, the capacity of cells to proliferate is prob­ ably maintained well into adulthood, if not old age. This capacity reflects a continuing ability of the pulp and more structurally and functionally complex) to provide odontoblasts for secondary dentin forma­ leads to loss of telomeres with age and hence the tion. The predominant cell in the pulp, the fibroblast, loss of the ability to grow. Others have found that shows and perhaps dictates the pattern seen in the an enzyme that elongates telomeres overcomes pulp cell population as a whole. Immune cells and age-related shortening51·52; however, this enzyme is macrophages show a varied pattern of presence and not found in normal somatic cells.52 In contrast, telo­ activity within the aging pulp. For example, immu­ meres from sperm DNA did not decrease in length noglobulin G levels seem to diminish with age (in as donor age increased, suggesting that a mecha­ animals), likely resulting from fewer lymphocytes, as nism for maintaining telomere length, such as telom­ does the number of Class II major histocompatibility erase expression, may be active in germ-line tissue.53 complex-expressing cells. Te lomeres' DNA sequences cap the ends of all Connective tissue changes are also observed in eukaryotic chromosomes and shorten during repli­ aging pulps. The amount and type of collagen pres­ cative aging of normal cells. Variations in the initial ent in the pulp change with advancing age, leading length of terminal restriction fragments account for to an overall increase in fibrosis and levels of calci­ much of the variation in fibroblast replicative capaci­ fication. This fibrosis occurs even though collagen ties, and it has been found that the existence of a synthesis appears to diminish in older teeth. This critical telomere length in senescing cells occurs in finding is consistent with a reduction in the level of aging.54 A more detailed discussion of the telomere's matrix metalloproteinases (ie, MMP-2, -8, -9) with role in replicative senescence can be found in other collagenase activity or possibly an increase in tissue publications. 5s.-<>3 inhibitors of MMPs, leading to a reduced turnover Taken together, studies of replicative senescence, of existing collagen. In addition, the fibrous sheaths oxidative stress, and telomere shortening indicate associated with blood vessels and nerves persist that cells and tissue age in a manner that appears even as the structures diminish in number with age. to be well controlled. Similar studies should be Finally, there is a relative (apparent) increase in the done using pulp tissues and processes to define the amount of fibrous connective tissue due to the changes that occur with aging of the teeth. reduction in volume of the "pulp chamber in older

425 www.shayanNemodar.com Aging and the Pulp individuals. As later described in more detail, the 10-week-old), adult (14- to 24-week-old), and aged occlusion of the canal is due principally to the accu­ (1- to 5-year-old) Wistar rats. Results indicated that mulation of secondary dentin (see also chapter 2). ED1-labeled cells were maintained throughout life, but a significant decrease of OX6-positive (Class II major histocompatibility complex-expressing) cells Histologic and histomorphologic analyses was observed. The density and composition of pulp cells expressing macrophage-associated antigens Several well-controlled animal studies have focused decreased with increasing age, most probably relat­ on age-related changes in cell proliferation and ed to changes in the immunologic defense potential collagen turnover. Early studies on the cell kinetics of the pulp against infection. of aging in rat molar pulp cells found detectable A later study used rats in two age groups. The DNA synthesis up to 400 days of age, indicative of dental pulp monocyte/macrophage system response continued cell division and cell turnover in older to cavity preparation in animals 12 and 18 months animals. The proliferative activity of the pulp was old was compared to that in younger animals 3 and greater in younger rats, while the volume of pulp 6 months old. No differences were found in the tissue was reduced by the continuing dentin appo­ monocyte/macrophage defense mechanism to injury sition in aging animals.68 Using stains and silver in either group, indicating the possibility that the impregnation for collagen and reticular fibers, his­ dental pulp retains the ability to defend itself against tologic studies found changes in connective tissue injury during the aging process.76 collagen.69 Examination of the cellular dynamics In addition to changes in cell number, there are of the incisor pulps of different-aged rats showed also age-related alterations in the levels and distri­ no consistent change in odontoblast number with butions of the cytoskeletal proteins actin, cytokera­ advancing age. However, a slight but continuing tin, and vimentin. The levels of these proteins dimin­ reduction of basal pulp cells occurred throughout ish with age, and the decreases are most striking in life.70 Thymidine-labeling studies indicate that pro­ odontoblasts.72.73 liferative activity of fibroblasts contained in the pulp There are also marked reductions in odontoblast and periodontal ligament is reduced with age.71 The processes.75 Although it is currently impossible to pattern of decreased activity seems to follow that of determine what initiates age-related changes in human pulp, with DNA synthesis showing a signifi­ odontoblasts, one explanation might be alteration in cant decrease over time. Increases in fibrosis may be the blood supply.76 Capillaries form a dense plexus due to increases in the age-related accumulation of about 10 µm beneath the predentin. As animals age, insoluble collagen that accompanies decreased cel­ odontoblasts lose their cytoplasmic processes; the lularity. In bovine studies, collagen concentrations loss of fenestrations in the capillaries coincides with increased from about 9% to 25% as pulp matured, a reduction of odontoblast function. Subsequently, and the ratio of type Ill to type I collagen also odontoblastic capillaries are lost and there is evi­ increased, suggesting a substantial increase in type dence of degenerating vessels, cells, and extracel­ Ill synthesis during aging.72.73 lular debris near the incisal edge of the tooth. Thus, Animal studies have also found age-related the changes in odontoblast function may be linked changes in the immune system in dental pulp. Exam­ to the loss of pulpal vascularity that occurs with age77 ination of immunoglobulins in bovine dental pulp (see also chapter 6). found that immunoglobulin G levels decreased as Histologic analysis on human teeth confirms that the animal aged.74 Alterations of the levels of immu­ with age comes a reduction in cell numbers and a noglobulins may indicate maturation of the animals narrowing of the pulpal space.78 Similarly, when the and may reflect physiologic changes rather than the cellularity of the outer cell-rich zone of pulp was presence of localized pathoses. This finding is con­ compared to the less cellular middle zone, it was sistent with other evidence that the overall immuno­ found that the cell number decreases in all three defense potential of the pulp decreases in older ani­ zones starting at 20 years of age; by the age of 70 mals75 (Figs 18-2 and 18-3). The distribution of pulp years, the total cell number is reduced by 50%.79 cells expressing reactivity to monoclonal antibody In addition to these quantitative studies, Murray ED1 was examined immunohistochemically in the et al9 confirmed and quantified more precisely the mandibular first molars of developing (newborn to reduction in cell density and compared the pulp

426 www.shayanNemodar.com Age-Related Changes in the Pulp

Fig 18-2 ED2-positive /...., . cells in the coronal pulp of the mandibular first molar of a 24-week-old rat. Positively stained cells are predominantly irregular or dendritic (OX6 stain; original magnification x 130). (Reprinted from Okiji et al75 with permission.)

.� 'I

... � ... . \ Fig 18-3 Distribution of macrophages in )J,,j 'l \' the coronal pulp of the mandibular first molar t of a 1 V2-year-old rat. Positively stained cells are ,,:;" / predominantly elongated (OX6 stain; original magnification x 130). (Reprinted from Okiji et c al75 with permission.)

in the crown with the pulp in the root. In compari­ In another histologic analysis of 100 noncarious son with younger patients aged 10 to 30 years, the molars from males and females aged 15 to 75 years, number of crown odontoblasts decreased by 15.6% Bernick and Nedelman84 found that aging was asso­ for all teeth and the density of root odontoblasts ciated with increased calcification of the extracel­ decreased by 40.6% in patients 50 to 59 years old. lular matrix, decreased numbers of blood vessels Similarly, the density of fibroblasts decreased by and nerves, increased fibrosis (collagen sheaths), 26.9% in the crown and by 41.3% in the root with increased collagen fiber thickness, changes in the aging.9 chemical properties of collagen fibers, and fusion A review of age-related changes in the human of van Korff fibers in the odontoblastic area. The pulpodentin complex divided the aging process into prominence of collagen fiber bundles was attributed four groups, distinguished by changes resulting from to the persistence of the connective tissue sheaths in physiologic aging rather than irritant-based pathol­ the narrowed pulp chamber after loss of the vascular ogy or trauma.80·81 The measured cell density of the and nerve supply and not to continued formation pulp decreases by about half as a person ages from and reorientation of collagen fibers during the aging 20 to 70 years,82 as odontoblasts decrease in num­ process. This finding is consonant with the conclu­ ber and become smaller and flattened. An apparent sions of other investigators.80 · 85 increase in the number of collagen fibers results from Clinical studies have also documented age-related a reduction in space in the pulp caused by secondary changes in collagen in dental pulp. In human third dentin formation, which gives the appearance that molar pulps from patients aged 16 to 40 years, there there are more fibers in the remaining space.83 was a substantial increase in calcium and decrease

427 www.shayanNemodar.com Aging and the Pulp

80 80 � E 70 70 ..... 6 60 • 60 �

x �0 50 50 • c: • � •• c: • ·e 40 GJ 40 • ..... • Cl .!!! 30 ..!!! 30 • • • � • . A 0 ••• • • u • c: 20 � 20 • • • GJ • • • • Cl • • • ..!!! 10 10 0 • 0 B u 16 18 20 22 24 26 28 30 32 34 36 38 40 16 18 20 22 24 26 28 30 32 34 36 38 40 Age (y) Age (y) a b

Fig 18-4 (a) Concentrations of reducible collagen cross-links in pulp from teeth removed from patients at different ages. Closed circles and line A represent dihydroxylysi­ nonorleucine (DHLNL). Open squares and line B represent hydroxylysinonorleucine (HLNL). Open circles and line C represent lysinonorleucine (LNL). Slopes for A, B, and C were calculated using best-fit regression analysis. (b) Collagen content of human dental pulp at different ages. The slope of the line, calculated using best-fit regression analysis, is not significantly different from 0. (Reprinted from Nielsen et al8' with permission.)

in levels of dihydroxylysinonorleucine (DHLNL)81 (Fig More recently, a transcriptome analysis was con­ 18-4a). This modified amino acid is a major cross­ ducted to clarify the genetic changes that underlie linker that binds collagen fibers together and can be the histologic modifications in the dental pulp with detected by the addition of reducing agents. Because aging.86 Microarray analysis of third molars of 18- to collagen maturation is characterized by the presence 20-year-old and 57- to 60-year-old patients revealed of reducible cross-links, this study demonstrated that several differentially expressed genes that were cat­ collagen synthesis in the coronal pulp decreased with egorized as encoding growth factors, transcriptional age; this change was accompanied by a decrease in regulators, apoptosis regulators, and components of collagen concentration in terms of both dry weight the extracellular matrix. In young dental pulp, high and total protein (Fig 18-4b). expression levels were detected for genes involved Another study evaluated 239 noncarious human in cell proliferation, cell and tissue differentiation, teeth in individuals from 10 to 78 years of age.82 and development, as well as in the immune, lym­ The older dental pulps were characterized by a phatic, and hematologic systems; in older dental relative compression of collagen fibers that resulted pulp, genes involved in apoptosis were more highly from accumulated dystrophic or degenerative calci­ expressed. Higher expression of genes for synthe­ fications, giving an appearance of fibrosis. Although sis products (collagenous and noncollagenous) was increased fibrosis was not actually observed in this noticeable in the younger dental pulp, whereas study, others have reported increased fibrosis and genes encoding specific markers such as dentin calcification radicularly that is more severe than that sialophosphoprotein (DSPP), ameloblastin, or osteo­ found coronally.83 nectin were highly upregulated in the older dental Clinical trials have noted distinct age-related pulp. Although proteomic experiments are needed patterns in cellular changes in dental pulp. Numer­ to confirm the differential gene expression at the ous star-shaped fibroblasts are seen in the pulp of protein level, these results are interesting because young individuals, yet they are diminished in size and they may be related to the intrapulpal calcification number in teeth from older individuals. The number and mineralization observed during aging. of odontoblasts and amount of predentin are also Other studies have evaluated whether tissue diminished as teeth age, indicating that fibrosis and matrix components change in aging dental pulp. cell depletion are a normal aspect of aging. One study compared third molar pulps of 17- to

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Fig 18-5 In the coronal and radicular Fig 18-6 In the pulp horn, two pulp, blood vessels are surrounded by layers of type VI collagen are adjacent type Ill collagen. Fibers and bundles to the odontoblasts. A thin line of very of fibers that are strongly stained intense fluorescence labeling is located extend between the blood vessels directly adjacent to the odontoblastic and the connective tissue matrix layer (large arrowheads). A second (paraffin section, immunofluorescence layer, consisting of fine fibrils (small microscopy; original magnification arrowheads), lies adjacent to this line X375). (Reprinted from Hillmann and (paraffin section, immunofluorescence Geurtsen89 with permission.) microscopy; original magnification x 100). (Reprinted from Hillmann and Geurtsen89 with permission.)

Fig 18-7 (a) Longitudinally arranged fibers of type V collagen (large Fig 18-8 Confocal laser scanning microscopy. Fibers of type VI collagen with arrowheads) are adjacent to the layer of odontoblasts (arrows). Some corkscrew pattern pass from pulp into predentin parallel to the long axis of the thin fibers extend between the odontoblasts (small arrowheads) (paraffin odontoblasts (arrowheads) of the coronal and radicular pulp (paraffin section; section, immunofluorescence microscopy; original magnification X375). original magnification x 500). (Reprinted from Hillmann and Geurtsen89 with (b) In the odontoblastic layer of the coronal pulp, immunolocalization of permission.) collagen type VI reveals corkscrew fibers passing from the pulp between the odontoblasts (arrowheads) (paraffin section, immunofluoresence microscopy; original magnification x 500). (Reprinted from Hillmann and Geurtsen89 with permission.)

25-year-olds with that of patients aged 50 years ing of types 111, V, and VI collagen is strong (Figs 18-5 or older.87 Using osteocalcin as an index of matrix to 18-8). With advancing age, fiber bundles of type production, the researchers found that osteocalcin I collagen increase in frequency and thickness while expression (presumably of odontoblast cell lineage) the fine fibrils of types Ill, V, and VI collagen disappear does not diminish relative to the explant cell popula­ or are replaced by thick fiber bundles (see Fig 18-7). tion. The authors concluded that, despite a reduc­ The connective tissue matrix appears condensed and tion in tissue volume and cell numbers, the pulps of stained homogenously in older individuals. aging teeth retain a capacity for dentin deposition. Another study evaluated matrix components in 332 human teeth in three age groups (10 to 30 years, Odontoblasts and aging 31 to 51 years, and 52 to 72 years).88 The results indi­ cated that collagen types I, II, V, and VI are present at Several studies have focused on age-related chang­ all ages. Staining of type I collagen is weak, and stain- es in odontoblasts and report a consistent reduction

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in numbers of cells in the odontoblastic layer. An linked to changes in biologic activity of the cells. early scanning electron microscopic study examined Simon et al93 showed that the phenotype also evolves cell processes in caries-free and attrition-free pre­ with time and that these modifications must be taken molars in 14- to 16-year-old patients and compared into account in the investigation on aging. In the them to those of 59- to 72-year-old patients.90 In the future, these animal experiments (on bovine teeth) younger pulps, the odontoblast processes extended should be reproduced on human cells to analyze the into the dentinal tubules, often reaching the den­ genomic evolution of the odontoblast with aging. tinoenamel junction. However, in the older pulps, This study also supported further existing similarities fewer processes were found in sclerotic dentin and between pulp cells and bone cells. DMP -1, which they never extended close to the dentinoenamel is expressed in osteocytes but not in osteoblasts, junction. is associated with the maturation of the odonto­ Dentinogenesis is a continuous process of matrix blast. Based on these results, it is tempting to con­ deposition throughout the life of a tooth (see also sider young and old odontoblasts as two different cell chapter 2). Primary dentinogenesis occurs during types, and some authors have even proposed renam­ development, leading to formation of the crown ing mature odontoblasts as odontocytes.94 and root of the tooth, whereas secondary dentin Odontoblasts may exhibit reduced function over is secreted throughout the life of the tooth and is time, even when their numbers remain stable. Odon­ responsible for the reduction in the size of the pulp toblast function, as measured by reactionary dentin chamber and root canals and the deposition of peri­ formation, was determined after dental injury (Class V tubular dentin.91 So far, no histologic difference has cavity preparations and restorations) to intact first or been described between primary and secondary second premolars of patients between 9 and 17 years dentin other than at the interface between the two of age.87 Although odontoblast cell numbers were tissues, which is delimited by a calciotraumatic line.92 maintained in this relatively young population, the The two types of dentin are secreted by the same older subjects had less reactionary dentin formation. cells, albeit at different times and rates. Odonto­ This intriguing study should be extended to evaluate blasts are actively secreting during primary dentino­ odontoblast function in the elderly, in whom greater genesis but become significantly less active during changes may be anticipated, with consequences for secondary dentinogenesis. endodontic treatment or tooth loss. The actual time of switching from the primary Odontoblast function is often considered as unal­ stage to the secondary stage is still not well defined. terable during the life of the dental pulp. Never­ The odontoblast transcriptome has recently been theless, the survival mechanisms that preserve cell investigated by microarray analysis.93 The results viability are still poorly understood. Recently, the showed that differential dentin secretion is associ­ autophagic-lysosomal system of human odonto­ ated with changes in transcriptional activity within blasts has been investigated95 to analyze the mecha­ the cell. Although the two types of dentinogenesis nisms that maintain the functional viability of these are reported to differ in their rates of matrix deposi­ secreting cells. Odontoblasts were found to develop tion, expression of dentin matrix protein 1 (DM P -1) an autophagic-lysosomal system with large autopha­ and osteocalcin genes was upregulated in the mature gic vacuoles that expressed the autophagosomal odontoblasts, while expression of type I collagen, (LC3) and lysosomal (LAMP2) markers in an age­ DSP P, transforming growth factor [31 (TGF-[31), and related pattern, indicating organization of a dynamic TGF-[31 receptor genes was downregulated. Microar­ autophagic machinery. In this study, the authors ray analysis highlighted 574 differentially regulated suggested that autophagic activity in odontoblasts genes involved in the p38 mitogen-activated protein is a fundamental mechanism to ensure turnover and kinase (MAPK) pathway, in which PTPRR, NTRKK2, degradation of subcellular components. A reduc­ MAPK13, MAP2K6, and MKK3 were strongly impli­ tion in the efficacy of this system-during aging, for cated. example-might compromise cell viability and den­ It has already been shown that the morphology tinogenic secretory activity at the "old odontoblast" of the odontoblast changes over time (cylindrical stage. in younger cells and flattened in older cells) and is

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Dentinogenesis and aging in the height of the coronal pulp cavity in 134 adult men and women 20 to 80 years of age. They report­ Aging studies related to changes in dimension of ed correlation coefficients that ranged from -0.650 the pulp chamber and root canal spaces have been to -0.799 and were statistically significant for both undertaken with the aid of radiographs, microcom­ genders in both premolars and molars. The results puted tomography (µCT) scans, and scanning elec­ also allowed for the estimation of subject age with tron microscopy (SEM). Some of these devices are an error of ±5 years. research tools and cannot be used on a regular basis A similar study used 197 panoramic radiographs clinically, although they are now appearing in legal of patients 19 to 75 years of age.103 Six teeth were cases. The focus of this work has been to describe selected for measurement: a maxillary central incisor, age-related changes in terms of apposition of den­ lateral incisor, and second premolar and a mandibu­ tin in various areas of the coronal and radicular lar lateral incisor, canine, and first premolar. Multiple pulp canal space. The use of SEM and radiographic regression analyses were used with measurements of devices demonstrates these age changes; these the relationship between chronologic age and the studies have been carried out by a disparate group two-dimensional dental pulp size. The data showed of investigators, including clinicians, anthropologists, that this approach is successful in correlating age and forensic scientists. from this type of film. SEM and radiographs were used to measure pulp chamber and root canal spaces in subjects aged 40 to 70 years and 40 to 97 years; both the pulp cham­ Biologic considerations ber and root canal spaces were found to narrow and become restricted with age.96 The changes occurred Aging induces several degenerative processes, mostly in a mesiodistal direction rather than corono­ including fibrosis, atrophy, loss of cellularity, decal­ apically. cification, and degeneration of odontoblasts.84•104 Raman spectroscopy characterized the chemi­ These phenomena depend on a dysfunctional cal composition and the stages of increased dentin homeostatic mechanism. It is also known that mes­ deposition.97 Thirty teeth were analyzed, and the enchymal cells in pulp have the potential for miner­ results led to a good age prediction. Other studies alization, based on the formation of dentin induced suggested the use of CT to determine age-related by a variety of stimuli. changes. These studies were carried out, for the Quantification of various biologic substanc­ most part, by forensic scientists using material avail­ es from dental pulp and dentin have been used able through examination of skeletal remains.98 All of to determine the age of subjects. In one study, these studies were able to estimate the ages of the small pieces of dentin were used to assess mtDNA deceased by examination of dental pulp spaces. removed from third molars of 21 individuals aged The use of µCT is a more recent development. 15 to 85 years.105 Amplification and agarose gel The devices are very expensive and generally not electrophoresis of the amount of mtDNA were semi­ available except at a few dental schools. They are quantified from the intensity of stained bands in the used primarily in orthodontic programs and are gel. The results showed that the amount of mtDNA considered research tools rather than devices for declines with age. The method could be used to diagnostic or treatment-outcome studies.99-101 Stud­ determine tooth age. ies with µCT and cone-beam CT can determine age Age can be estimated from human dental pulp changes when patients are scanned. DNA based on telomere shortening. One study Normal dental radiographic studies have also found that the terminal restriction fragment length been used to determine age-related changes but tends to shorten with aging.106 Several studies with varying results. This type of study can be done attempted to estimate chronologic age in cadavers, using radiographs of patients of record or in schools human remains, and living human beings by exam­ and private practices and are relatively routine in ining changes in certain biologic substances in the their application. Internal review boards regulate dental pulp. One study found that impaired repair radiographic studies, which are usually conducted in of pulp and dentin in aged patients is partly due to orthodontic programs. lgbigbi and Nyirenda1 02 mea­ a decrease in the proliferative ability of human pulp sured the height of the tooth crown and decreases cells from aged donors.107 The in vitro proliferative

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life span of human pulp cells from young donors was While cell behavior during aging has begun to be longer than that of cells from older donors. Growth documented, the effect of aging (microenvironment) rates and alkaline phosphatase activity decreased on cells is less investigated. In a recent study, a Chi­ with increasing donor age. nese team investigated the potential effect of aging Characterization of aging can be measured by of the extracellular matrix on cells themselves. They expression of other substances in the dental pulp. exposed aged pulp cells to juvenile-conditioned Connexin 43 is a protein for gap junctions; reverse medium and juvenile cells to adult-conditioned transcription polymerase chain reaction detected medium. Adult pulp cells cultured with juvenile­ its expression in all pulp samples.108 However, con­ conditioned medium showed enhanced proliferation nexin 43 was abundantly expressed in young adult but a reduced ability to differentiate. In contrast, dental pulps, while its expression was dramatically young cells cultured with adult-conditioned medium decreased in aged dental pulps. The same research­ changed their behavior and proliferated and differ­ ers used real-time reverse transcription polymerase entiated as adult cells.113 Such a rejuvenation pro­ chain reaction to investigate expression of osteo­ cess has already been described for stem cells in the calcin messenger RNA (mRNA) in third molar dental course of nuclear reprogramming.114 pulps from healthy 17- to 23-year-olds and sub­ While methodologies necessarily differ according jects older than 50 years.109 Osteocalcin RNA was to the biologic substance being studied, it is appar­ expressed in all samples, but expression decreased ent that many pulpal substances can serve as mark­ in aged pulp. This change may be associated with ers of age-related changes in pulp tissue. Markers loss of viability and may be a characteristic of aging. that decrease with age may impact the retention of In another study, a Japanese group highlight­ viable pulp tissue, leading to situations that increase ed differential expression of core-binding factor a1 the need for root canal treatment as a person ages. (Cbfa1), vascular endothelial growth factor (VEGF), It also seems evident that if aging has direct effects and heat shock protein (HSP-27) mRNAs in young and on cellular behavior, the cellular microenvironment, old odontoblasts in rat teeth. Cbfa1 is a transcription and extracellular matrix components, then microen­ factor required for osteoblast maturation and is also vironmental effects related to aging must also have expressed in odontoblasts when they differentiate an effect on a cell's biology. from preodontoblasts. Expression of Cbfa1 mRNA was higher in young rats than in adult rats, while Blood vessels expression of VEGF and HSP-27 mRNAs was higher in The pulpal vascular system is extensively reviewed in the adults. The authors concluded that a self-defense chapter 6. In general, the dental pulp receives blood system in odontoblasts operates differently depend­ supply via arterioles that enter the apical formina ing on the age of the tissue: It promotes calcification and branch to give rise to a capillary network or in young teeth but expresses self-defense proteins plexus, some of which is juxtaposed to the pre­ and stimulates regeneration of blood vessels in adult dentin, and odontoblastic layer. Drainage of blood dental pulp cells.110 occurs via venules that exit the tooth through the Various signaling pathways are involved in all apical and lateral foramina. There is some evidence biologic processes, and senescence is no excep­ for the existence of arteriole-to-arteriole, arteriole­ tion. For example, the Notch signaling pathway has to-vein, and vein-to-vein anastomoses, suggesting been implicated in odontoblast differentiation and that there is extensive regional control of blood flow is activated during reactionary dentinogenesis,111 but to the pulp.115 it is also known to be involved in the maintenance of The microvascular supply to the pulp is small dental stem cell plasticity by regulating odontoblast relative to the volume of tissue that is supports. The differentiation.112 Recently, it has been demonstrated number of vessels entering the tooth diminishes that the Notch signaling pathway is also involved with age and the vascular plexus becomes reduced, in the senescence process: When this pathway is sometimes appearing entirely absent. Additional blocked by experimental methods, cell prolifera­ age-related changes include intimal hyperplasia of tion was found to be decreased, and a marker of arterioles, narrowed vessel lumens, and calcifica­ senescence (SA-[3-Gal in the model used) was over­ tion of the vessel wall. In a study of 23 9 pulps from expressed.112 subjects 10 to 78 years of age, researchers observed reduced vascularity in coronal pulp with increasing

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Fig 18-9 (a) High-magnification view of the central portion of the pulp chamber of an incisor from a 30-year-old patient. The interior vascular structures are reduced in number, and the peripheral arcade is less intense (original magnification x 100). (b) High-magnification view of the pulpal structures of an incisor from the older age group (40 to 70 years). Centrally located major ( vessels are visible, although interrupted, and the subodontoblastic capillary plexus is absent (original magnification x 100). (Reprinted from Bennett et al116 with permission.)

a

age, although radicular vascularity was observed, ber of vessels, often having only one primary arterial indicating the presence of an effective, anabolically vessel entering the tooth compared to three or four active tissue. vessels in the 10- to 20-year age group (Fig 18-9). In addition to the changes within the vessels The peripheral capillary plexus was also reduced or per se, age-related diminution in the dimensions entirely absent in most pulps of the older age group. of the pulp space also occur, caused by secondary An additional study compared teeth from individ­ dentin formation (also dystrophic calcification and uals younger than 20 years and individuals aged 40 tertiary dentin formation). This process of space to 70 years and demonstrated a highly vascularized reduction also results in a marked narrowing, and tissue in the younger group; vessels of arteriole size sometimes obliteration, of the medium-sized vessels were found in the coronal portion of the tissue of and capillaries. younger teeth.117 The pulps from older patients were Odontoblast activity and viability are intimately characterized by a gradual narrowing of the circum­ linked to the vascular supply, particularly the supply ference of the pulp and vessels that became more from the capillary plexus located proximate to the prominent centrally. As secondary dentin forma­ layer of preodontoblasts and predentin. With the tion continued, the pulpal area and circumference age-related reduction (compression) of the feeder decreased, leaving only a thread of pulp tissue and arteriolar system to the pulp, there is an associated causing narrowing and elimination of medium-sized diminution of the capillary plexus, including vessel vessels and capillaries. degeneration near the incisal end of the pulp. There Another study evaluated changes in alkaline is also a loss of fenestration in the capillaries. phosphatase and adenosine triphosphatase activ­ It is highly likely that these marked age-related ity in three groups of patients (1 0 to 30 years, 31 to changes in the vascular supply to the pulp contrib­ 50 years, and 51 to 70 years). Results demonstrated ute to the diminution in the capacity of odontoblasts decreases in both enzymes with aging.118 The most to survive and produce new dentin matrix. To exam­ notable change in the expression of these phospha­ ine this question, one study of pulp vascularity col­ tases occurred in the endothelial cells of the capil­ lected single-rooted, permanent human teeth from laries. The study indicated that reduction of these individuals in three age groups: (1 0 to 20 years, 20 to substances would be accompanied by a reduction 40 years, and 40 to 70 years).116 With increasing age, in metabolic activity of the pulp with aging, which the teeth showed reduced terminal branching of certainly may indicate a finite ability of odontoblasts vascular structures and reduced numbers of vessels to form dentin. entering and exiting the apical foramen. Te eth in the A different study119 described the ultrastructural 40- to 70-year group demonstrated the fewest num- changes that occur in pulpal capillaries as a result

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of aging. Samples of dental pulps were obtained appears to parallel the age-related loss observed in from functional human teeth, and tissue from 10- to vascular supply described earlier. Indeed, the affer­ 17-year-olds and tissue from individuals more than 60 ent blood supply and the nerves constitute a neuro­ years of age was compared. The pulp tissue was pro­ vascular bundle that generally terminates together cessed using transmission electron microscopic tech­ peripherally. niques. Results demonstrated an endothelial cell layer Prior studies have demonstrated age-related characterized by the presence of numerous pinocy­ mineralization (calcification) of the endoneurium and totic vesicles and microvesicles, rough endoplasmic perineurium and ultimately the nerve proper and the reticulum, cisternae, free ribosomes, a small Golgi loss of the plexus of nerve fibers (plexus of Rasch­ complex, centrioles, microtubules, microfilaments, kow) that is located in the subodontoblastic layer. In and mitochondria. In the endothelial cell cytoplasm addition, the number of myelinated fibers diminishes of older pulpal vessels, pinocytotic vesicles, microves­ with age, and both myelinated and unmyelinated icles, and microfilaments were more numerous. Lip­ fibers show an increased threshold of response to id-like vacuoles, monogranular glycogen granules, stimulation. This increased threshold for stimulation and extensive Golgi complexes with dilated cisterns probably is due to both a loss of the total number of were also present, suggesting that capillary endothe­ fibers and a reduced terminal arborization of remain­ lium experiences morphologic changes that could be ing fibers. associated with advancing age. Detailed studies of age-related changes in pulpal Collectively, these studies of the aging dental pulp sensory neurons have been conducted in cats. In the demonstrate that vessels decrease in number and the incisor, the number of fibers (axons) increases with pulp chamber narrows with deposition of secondary age until about the third year and then diminishes dentin. Even within the context of a smaller tissue thereafter. The diameters of axons and nerve fibers volume, a diminished vasculature appears incapable become reduced in size, as does the length of the of supplying adequate nutrients to the tissue, result­ internode segments. Part of the reduction in pulpal ing in reduced metabolic activity. This combination of nerve supply may be the result of reduced numbers senescent changes probably affects the ability of the of receptors to nerve growth factor (NGF), which remaining tissue to react appropriately to an adverse serves as a trophic factor for a substantial proportion stimulus, resulting in reduced capacity of older indi­ of nociceptors. viduals to retain their teeth, even in a healthy envi­ Tw o effector substances (neuropeptides) impor­ ronment. The expectation is that elderly patients tant in mediating the inflammatory response­ may require an increasing number of restorative or calcitonin gene-related peptide (CGRP) and sub­ endodontic procedures to retain their teeth. The stance P-also diminish with age. This may weaken alternative is for these patients to lose their natural the potential for neurogenic inflammatory and heal­ teeth, diminishing the capacity to maintain a normal ing responses in aged pulp tissue (see chapters 7 diet and level of health.120 More studies are needed and 8). Collectively, these observations show a clear to investigate this clinical problem. loss of pulpal nerve supply with advancing age. These changes may result from some underlying Sensory nerves mechanism of aging that acts on neurons in a fun­ The innervation patterns of pulpal neurons and their damental manner. More likely, however, they result responses to injury are described in chapter 7. In from a combination of age-related events including general, it should be appreciated that nociceptor compression (as the pulp space becomes smaller responses to tissue injury protect the individual from due to secondary dentin formation), fibrosis and harm. When that response is diminished or absent, calcification, the loss of blood supply, and the dimi­ damage to the tissue may occur, necessitating clini­ nution in the fibroblast and odontoblast population cal intervention to prevent permanent damage and (sources of neurotrophic factors). loss of function. One study examined pulpal neurons from 150 The nerve supply to the dental pulp is a unique teeth in individuals aged 40 to 70 years.121 Calcifica­ tissue in humans in that its afferent innervation is tion occurred in 90% of all pulps. This was first seen in almost entirely nociceptors, including Ao and C isolated regions in the endoneurium and perineurium fibers. A reduction in the nerve supply to teeth of nerve fibers, although older specimens were char­ is well documented to occur with age. This loss acterized by mineralization of the entire endoneural

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Fig 18-10 (a) Thick section of the coronal portion of the pulp of a premolar Fig 18-11 (a) Electron micrograph of a cross section of axons in a premolar from a teenage individual. There is extensive branching of the pulpal nerves and from a 15-year-old subject. Unmyelinated axons form groups of varying sizes a rich subodontoblastic network. B, blood vessels; PN, pulpal nerve; N, nerve (original magnification x 6,000). (b) Electron micrograph of a cross section of fascicularis (Verhoeff's iron hematoxylin stain; original magnification x 50). (b) axons in a premolar from a 34-year-old subject. Unmyelinated axons are usually Thick section of the coronal portion of the pulp of a molar tooth from a 50-year­ in small groupings (original magnification x 6,000). (Reprinted from Johnsen et old individual. Only the pulpal nerve is demonstrable; the cuspal branches al123 with permission.) and subodontoblastic network are absent. PN, pulpal nerve; B, blood vessels (Verhoeff's iron hematoxylin stain; original magnification x 50). (Reprinted from Bernick121 with permission.)

or perineural connective tissue and often appeared electrical pulp tester than did older teeth with fewer to have a calcified ring around the nerve fibers. The fibers. younger control group had no calcifications and A study in cat incisors showed an increase in the demonstrated evidence of pulpal nerve branching number of axons in the apical region up to the third in the subodontoblastic plexus near the pulp horn year and reduced numbers of myelinated axons from region (Fig 18-1 Oa). In the sample of older pulps, 3 to 11 years of age.124 These axons were also small­ there was a decreased overall number of nerves, with er in relation to myelin sheath thickness. The infe­ few fibers seen in the subodontoblastic plexus areas rior alveolar nerve underwent retrograde changes, (Fig 18-1 Ob). The nerves that persisted in the pulps of probably due to pulpal axon degeneration, and the older teeth were often characterized by degenerative axons appeared to be of a rather transient nature. changes including fragmentation, beading, and retic­ In a comparison study, the same results were seen ulation. This decrease in nerve quality and quantity in feline primary incisors but with the added aspect may explain the reduction in pulpal sensitivity anec­ of resorption.125 One possible explanation for the dotally reported in aging individuals. pulpal axon degeneration seen in these teeth could A quantitative assessment of sensory nerve be the early disappearance of odontoblasts, as the development in human premolars was made in teeth axons are closely associated with these cells. from subjects in four age groups (11 to 15 years, 20 In another study, pulps from five healthy cats (3 to to 35 years, 35 to 50 years, and 50 to 71 years).122·123 10 years of age) displayed an age-related decrease The teeth were tested with an electrical pulp tester in the number of pulpal axons, nerve fiber diam­ prior to removal and then examined for numbers eters, and intermodal lengths.126 The decrease in of axons present in the apical third of the pulp. The intermodal lengths may be due to demyelination results showed that myelinated axons were greatest and remyelination, as aging fibers exhibited qualita­ in number in subjects 15 years of age or older, with tive changes in their myelin sheaths. Age changes a trend to fewer myelinated axons in the older age in the peripheral nervous system may be related to groups (Fig 18-11 ). In older teeth, small, unmyelinat­ neuron aging, giving rise to distal axon degenera­ ed axons predominated. Younger teeth, with larger tion, but may also be due, as noted, to age-related numbers of myelinated and unmyelinated fibers, had changes of the target tissue. a lower threshold of response when tested with an

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There is an age-related change in the ratio of exhibit appropriate neuropeptide responses to tissue myelinated to unmyelinated neurons in dental injury despite several age-related tissue changes.130 pulp. One study evaluated the variation in numbers A related study analyzed innervation of pulp in of pulpal myelinated nerves in subjects 10 to 72 young (6- to 8-week-old and 3-month-old) and older years of age and reported that the total numbers (5- to 12-month-old) mice with a null mutation in decreased with age, particularly at the expense of the p75 gene and compared the results with age­ myelinated fibers.127 The decrease in sensory A fibers matched, wild-type controls.131 The results showed may be related to reduced sensitivity to the percep­ intense CGRP immunoreactivity in pulpal nerve end­ tion of dental pain in aging patients. Another related ings of mutant mice but a gradual decrease in CGRP study measured myelinated and unmyelinated axon intensity in controls during aging. Collectively, these populations in the dental pulp and reported that the studies indicate that there is an age-related reduc­ pulps of older individuals showed a loss of small Ao tion in peripheral neurons and neuropeptide expres­ fibers and unmyelinated C fibers, with a proportion­ sion but that the aged pulp can mount an appropri­ ately greater decrease in the number of C fibers.128 ate neuronal response to tissue injury. Fried129 has reviewed these findings and reiter­ ated that aging involves both structural and neuro­ chemical regressive changes in pulpal innervation. Response to pulp testing He notes marked age-related decrease in pulp­ al CGRP- and substance P-like immunoreactivi­ Although an age-related reduction in the density of ty together with a reduction in NGF receptor-like pulpal afferent fibers may mediate reduced sensitiv­ immunoreactivity. These changes in neuropeptide ity, pulpal injury may still cause pain in the elderly. expression are not entirely due to loss of nerve fibers Indeed, the assessment of orofacial symptoms and because most aging pulps contain NGF receptor­ pain intensity was found to be the best predictor of positive fibers but lack neuropeptide expression. It is whether elderly individuals utilize dental care, sug­ important to understand that these changes appear gesting that some level of nociceptor activation may as a physiologic response to aging. still exist in the elderly and prompt the seeking of However, an important question remains: What is such care.132 the functional significance of an age-related reduc­ In contrast to the prevalence of age-related ana­ tion in peripheral neuropeptide levels? It is well rec­ tomical studies, there are relatively few studies eval­ ognized that CGRP and substance P modulate neu­ uating pulpal response to testing in the elderly. rogenic inflammation and healing (see chapters 7, 8, Anecdotal evidence indicates that dental proce­ and 11). Comparatively few studies have evaluated dures evoke less discomfort in older individuals and age-related decreases in neuropeptide response that the requirement for local anesthesia is often and modulation of inflammation caused by opera­ reduced. tive cavity preparations. One study compared pulpal Maturational status of the tooth is important from neuropeptide responses to tooth preparations in the standpoint of responsiveness to pulp testing. young (3- to 4-month-old) and old (1- to 2-year-old) Pulp testing is often ineffective in older patients, rats.130 Examination of the control pulp revealed that especially if they are extremely aged and their teeth older animals had a substantial reduction in levels of have a history of caries and restorations (ie, due the low-affinity nerve growth factor receptor (p75- to tertiary dentin formation and loss of innervated NGFR). The authors concluded that this might be a dentin).133·134 Others have replicated this finding of biochemical marker of pulpal aging. After injury, the reduced responsiveness to thermal testing in the neuropeptide levels were increased in both young elderly.13s,136 and old rats in pulp adjacent to the Class V prepara­ However, this age-related reduction in pulpal tion site. responsiveness may be modality specific; in most The older animals displayed a greater proportion­ (but not all) studies , no differences in pain threshold al neuropeptide response near the injury than did the to electrical stimulation are found between young younger animals. This enhanced response could be and elderly patients.137·138 A stimulus-dependent due to reduced pulpal volume or to lower basal lev­ difference in pulpal pain perception may be due to els. In either case, the results indicated that older rats aging-related changes in pulp anatomy. Secondary

436 www.shayanNemodar.com Age-Related Changes in the Pulp

Mental foramen

Neural activity • Preamplifier • Oscilloscope • Amplifier ._ Data recorder

Com!uter ,._____j (Multianalysis program) a b

Fig 18-12 (a) Experimental setup for microsurgery. Neural activity is recorded with an enamel-coated, needlelike tungsten microelectrode inserted precutaneously through the mental foramen into the inferior alveolar nerve. (Reprinted from Ikeda and Suda 139 with permission.) (b) Setup for pulpal testing with electrical stimulation and thermal testing (heat and cold). The stimulating electrodes were copper disks soldered to copper wires placed on the center of the labial surface of the dried tooth and cemented with silver-reinforced glass ionomer (which has impedance significantly lower than that of other materials). (Courtesy of Dr H. Ikeda and Dr H. Suda.) (c) Electrical readout of results from electrical and temperature stimulation. (Courtesy of Dr H. Ikeda and Dr H. Suda.)

dentin deposition, narrowing of the pulp chamber, mineral apposition of tubules impaired nerve activa­ and closing of tubules could decrease thermal con­ tion, especially by heat, as per the hydrodynamic ductivity, leading to a longer latency or the need for mechanisms (Fig 18-12). a greater stimulus intensity to reach a temperature Finally, the decreased vascularity and nerve content level sufficient to activate primary afferent nerves. of the pulp itself must also contribute to decreased Changes in the structure of secondary dentin that response to stimulation in older individuals. limit fluid movement in dentinal tubules may also explain why older subjects are less responsive to cold stimulation. Pulp stones Most recent studies concerning dental pulpal response to various stimuli report the use of vari­ Pulp mineralization is commonly observed on bite­ ous devices (pulse oximetery, laser Doppler flow­ wing radiographs. Several factors can induce this metry, temperature change) to detect and provide pulpal response, and aging is one of them. a response or nonresponse ending with a definitive Two types of calcified bodies in the dental pulp diagnosis. However, because limited data have been have been described140: (1) a full mass filling the gathered on the correlation between pulpal nerve pulp chamber with epithelial remnants surrounded activity and sensation from intact human teeth, a peripherally by odontoblasts and (2) several pulp study used microneurography to examine this rela­ stones, compact degenerative masses of calcified tionship to determine changes in response as a func­ tissue. Many studies confirm the influence of aging tion of age. Three groups of individuals were tested: on pulp stone formation. In a study of 519 patients 18 years, 38 years, and 64 years of age.139 Ratings of (with an age range of 18 to 54 years) and 13,474 perceived pain intensity to thermal stimulation were teeth, Gulsahi and coworkers141 confirmed that the made using a visual analog scale. Findings showed prevalence of pulp stones increases with age and is that mean conduction velocities correlated closely significantly higher in molars than in premolars and with age. With advancing age, the percentage of incisors. They could not find any significant relation­ subjects whose teeth were not sensitive to ther­ ship between pulp stones and gender, systemic mal stimulation increased. In older tooth pulps, the diseases, impacted third molars, condition of the decrease in number of fast-conducting afferents and crown, or dental anomalies. These results were con-

437 www.shayanNemodar.com Aging and the Pulp firmed in another study by observation of panoramic Various techniques have been utilized to study radiographs of 247 patients.142 Although pulp stones physiologic deposition of secondary dentin through­ can be related to aging, no relationship has been out life. One study evaluated ground sections from found between pulp calcification and renal disease 273 maxillary central incisors divided into 14 5- or carotid artery calcification.142-144 year age groups and demonstrated an age-related increase in cumulative secondary dentin forma­ tion.149 Young teeth (6 to 11 years old) demonstrated Dentinogenesis metamorphosed (transparent) tracts at the incisal and cervical areas. Te eth from teenagers (11 to 15 As noted earlier, secondary dentin formation is a years old) showed initial signs of irregular dentin major contributing factor to the volumetric loss formation (fewer tubules) (Fig 18-13a), and the (compression) of the soft tissue space of the pulp prevalence of irregular dentin increased in older in­ (see chapters 2 and 3). In secondary dentin forma­ dividuals as dentin was deposited on the lingual walls tion, odontoblasts deposit new dentin in a process of the coronal samples. The oldest teeth had suffi­ that appears to occur continuously throughout adult cient amounts of secondary dentin to virtually obliter­ life, even in the absence of dental trauma and infec­ ate the coronal space (Figs 18-13b and 18-14). Tw o tion. This distinguishes secondary dentin from ter­ types of secondary dentin apparently were formed tiary dentin, which forms only in response to injury or slowly: (1) transparent dentin increasing from the infection. periphery of the crown and root inward toward the Studies of secondary dentin formation in erupted pulp with increased age and (2) secondary dentin teeth indicate that the process begins in the coro­ increasing circumferentially in the remainder of the nal portion of the tooth and extends apically over coronal pulp space. time. In contrast, impacted but otherwise apparently Another study used light microscopy to measure healthy teeth show the reverse pattern, with most the formation of secondary dentin in 240 central inci­ of the new dentin formation occurring apically.145 sors.151 Te eth from subjects older than 30 years dem­ The constriction of the pulp space as a result of sec­ onstrated increasing deposits of secondary dentin. ondary dentin formation does not occur uniformly Several studies have attempted to use these around the interior root surface. For example, in structural features to develop a method to iden­ subjects covering an age range of 10 to 97 years, it tify the age of a tooth.152·153 Of the various indices was found that the pulp chambers and root canal assessed, the transparency of radicular dentin and spaces became constricted in the mesiodistal but the magnitude of secondary dentin formation had not the faciolingual direction.96·146 the highest direct correlation with age. Given the The effect of aging on the patency of den­ apparent steady closure of the pulp chamber with tinal tubules depends on the cumulative effect of age, others have suggested that measurements age-dependent (eg, secondary dentin) and age­ of pulp chamber or root canal dimensions can be independent (eg, tertiary dentin) processes. One study used either as a biomarker for the aging process or reported no difference in tubule diameter and tubule to establish, from a forensic perspective, the age at density between younger or older subjects (8 to 25 death of cadavers or skeletal specimens.153 However, years old versus 40 to 60 years old).147 A reduction in the reliability of this measurement has been ques­ dentinal tubules may occur in still older individuals tioned because the teeth of certain aging individuals (older than 60 years of age) or may occur in relation to show no detectable change in canal size even when deposition of tertiary dentin (see chapters 2 and 3). followed for a period of more than 10 years.146 Age is the principal determinant (risk factor) for Other investigators have focused on using the the diminution of pulp size over time. The rate of accumulation of mineralized peritubular dentin as an pulp size reduction (secondary dentin formation) index of aging. Peritubular dentin forms centripetally may become slower in the elderly and may be slow­ in dentinal tubules as an individual ages, reducing er in women than in men.148 Although a reduction tubular diameters in older people.145·154 Studies in in secondary dentin formation may be related to a human teeth indicate that the thickness of peritubular smaller or less active pool of odontoblasts, gender­ dentin, but not tubular diameter, could be used as an related differences have been attributed to endo­ indicator of age. Others have suggested that the rela- crine factors.96

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Fig 18-13 (a) Low-power photomicrograph of an unstained central section of a maxillary central incisor ground in a labiolingual direction. The appearance is typical of that of the 11- to 15-year age group. The primary dentin and the apex are completed. There is no attrition, but the earliest stage of irregular secondary dentin formation is visible, mostly on the lingual wall of the pulp chamber. The transparency of the primary dentin of the root is unusual (original magnification x 20). (b) Low-power photomicrograph of a maxillary central incisor ground in a labiolingual direction. The central incisor is from a subject in the 71-year and older age group. The irregular secondary dentin fills the entire pulp chamber of the crown and extends down to the apical third of the root canal. This figure shows the culmination of the trend toward increase of irregular secondary dentin formation and metamorphosis of primary dentin with age (original magnification x 20). a (Reprinted from Philippas and Applebaum149 with permission.)

Fig 18-14 Radiographs of the same individual at 58 years old (a) and 77 years old (b). Note the almost complete obliteration of the root canal space coronoapically. No caries, restorations, or extreme occlusal wear is present. (Reprinted from Woo'"° with permission.)

tionship between the two factors may be a parameter the rate of secondary dentin formation was not lin­ for age estimation.155 ear.160 While there were increases in the thickness of Senescent changes in teeth are not the con­ secondary dentin over time, the increases did not sequences of trauma or infection but everyday approach those seen in erupted teeth, indicating usage and appear to be unavoidable. This point was that the formation of secondary dentin may be a stressed by Ketterl104 in a comprehensive review of cumulative process occurring in functioning teeth.161 age-related changes in the mineralized and soft tis­ Several studies examined pulp cell population sues of the tooth, including the adjacent periodonti­ in rats, demonstrating reductions in odontoblasts um. For example, older pulps have increased miner­ and pulpal fibroblasts over time. Histomorphomet­ al content in teeth with both intact and worn coronal ric analysis found decreases in cell density in the dentin.156 In the pulp, the number, nature, proper­ incisors of Wistar rats.162 Irrespective of age, odon­ ties, and capabilities of the cells change over time.76 toblast and subodontoblast cell density decreased Deposition of secondary dentin causes narrowing significantly with increasing age, whereas fibroblasts of the root canal space, 157 reducing the amounts of showed small but significant increases with age. dentinal fluid and dentinal sensitivity. Ta ken togeth­ Animals can also be used to determine morpho­ er, the changes occurring in the pulp and dentin, genic changes in the size of pulp cells over time. while physiologic in nature, may increase the need Rat molars were perfused with gluteraldehyde at for clinical interventions to preserve the teeth. 19 days to 24 months, and sections were processed The rate of formation of secondary regular and for light and transmission microscopy. Odontoblasts irregular dentin may differ after dental restorative changed from a tall, columnar morphology in the procedures. In a study with monkeys, restorative coronal pulp chamber to a more cuboidal or flat­ procedures evoked a fourfold greater rate of tertiary tened shape near the apex.163 Using fluorogold to dentin formation than secondary dentin formation158; examine tooth permeability, a study was designed other studies, however, have confirmed the physi­ to test the effects of aging on vital rat teeth.164 Cavity ologic deposition of secondary dentin in relation preparations were placed in rat molars, and changes to aging.139·159 In a study of impacted third molars, in cellular content and structure were found to be

439 www.shayanNemodar.com Aging and the Pulp

age related and regulated by odontoblasts.165 Other The variation in size occurs because peritubular den­ changes found in neural activity were determined to tin increases as the distance from the pulp increases. be injury produced from cavity preparation. At the inner surface of coronal dentin, no signifi­ Lastly, analysis of the proteins and proteinases cant difference is noticeable between young and involved in dentin formation may aid in understand­ aged teeth, either in the number or the diameter of ing the mechanisms involved in aging processes. In tubules. The change in size of the tubules is directly dentin, synthesis of complex specialized extracellular related to the permeability of the dentin, which has matrices precedes mineralization (see chapters 2 and several clinical implications. 3). While dentin, unlike bone, generally is not remod­ In the root portion, a reduction in the size of eled, the unmineralized predentin is remodeled in the tubules as a function of patient age was dem­ response to a stimulus (eg, caries, trauma). MMPs onstrated by Pouezat in 197 5. 169 The average size have been implicated in the physiologic remodeling decreased from 3.75 µm in 18-year-olds to 1.50 µm of the dentin extracellular matrix. 166 A recent study in 65-year-olds. The mean increase in the volume of examined dentin proteins extracted from the per­ intertubular dentin from the younger group to the manent molars of patients aged 15 to 73 years for older group was 18%. analysis of the MMP gelatinase A. This enzyme has Another age-related process is the absence of been implicated in the mineralization of predentin the odontoblast process in the tubules 0.7 mm to form dentin.167 The data demonstrated that MMP beyond the pulp, which Osborn and Ten Cate con­ gelatinase A was present in most teeth of individuals sidered to be an essential requirement of advanced 20 years of age or younger but only in one tooth of histology.170 one patient 30 years old and in no teeth in subjects Dentin maturation is governed by increasing 40 years of age or older. The results suggest that the intertubular dentin thickness, by the formation of capacity to mineralize predentin may decrease with peritubular dentin, and by intratubular sclerosis by age, rendering the teeth of elderly individuals less apatite or whitlockite precipitation. Progressively protected from external stimuli.168 with age, the peripheral tubules are replaced by peritubular and intratubular dentin formations.91 lntratubular and intertubular dentin formation Clinical Implications of the In addition to secondary dentinogenesis and reduc­ Aging Pulpodentin Complex tion of the pulp space, a further process of dentin secretion occurs throughout tooth life. There is grad­ ua I growth of peritubular dentin along the entire Dentin is a permeable tissue, permitting the passage length of the tubules together with intratubular of fluid, molecules, and bacterial toxins in pathologic mineralization in the most pulpal part of the dentin. conditions. This permeability is extremely important lntratubular dentin formation reduces the size of to support the physiology and homeostasis of the the tubule, sometimes leading to full occlusion or pulpodentin complex because the presence of den­ total sclerosis of the dentinal tubules. The mineral tinal fluid inside the tubules maintains the vitality of deposit is composed of rhombohedral crystals of this tissue. Any change of permeability under physi­ whitlockite. This process progresses with age from ologic (such as aging) or pathologic (such as caries or the apical third toward the cervical area, obviously in infection) conditions perturbs the homeostasis and conjunction with retraction of the odontoblast pro­ can lead to pulpal disease, notably inflammation. cess. lntertubular and intratubular dentin secretion Maintaining the patency of the tubules is a key factor is under the control of odontoblasts, whereas the in maintaining the permeability, and conditions that other mechanism for occlusion of tubules is mineral modify this patency can have clinical repercussions. precipitation. As detailed earlier, tooth aging involves a gradual Differences in the peritubular organization increase in dentin mineralization and a reduction in between coronal and radicular dentin are notice­ tubule diameter. When tubule occlusion is complete, able, and these have clinical implications. The densi­ the structure is described as being transparent under ty of tubules and their diameter varies considerably. a light microscope and is associated with reduced

440 www.shayanNemodar.com Clinical Implications of the Aging Pulpodentin Complex

permeability of the tissue. The typical clinical mani­ radiographs do not reveal the actual types of dentin festation is diminution of pulpal expression in old present in calcified root canal systems, they pro­ teeth compared to newly formed ones because of vide a measure of age-related changes occurring the reduction in permeability.171 Although this diminu­ in root canal systems due to secondary or tertiary tion of permeability can be considered an advantage dentin formation. Cross-sectional radiographic sur­ in preventing the movement of bacteria and toxins veys indicate a consistent reduction in metrics used into the tubules, the reduction in size of the tubules to measure pulp chamber and root canal dimen­ is also a limiting factor for restorative considerations. sions.156-158·165·175·176 One study compared tooth types Because most bonding systems require the penetra­ to determine which type provides the most reliable tion of the resin to create tags inside the dentin thick­ data in age estimation.175 Canines showed the high­ ness, the partial sclerosis of the tissue considerably est correlation with patient age, and the radiolucen­ reduces the retention value of these products. cy of the root was the variable most clearly related to With regard to endodontic considerations, the patient's age.177 because bacteria are the cause of apical periodon­ More recent studies have demonstrated that titis, all potential niches of bacterial retention are an teeth provide several useful reference points that obstacle to bone healing. Reduction of size of the may indicate an individual's age. Secondary dentin tubules is a limiting factor in bacterial penetration to is deposited along the walls of the pulp chamber the depth of the dentin and can be considered an and roots, leading to a reduction in the size of the advantage. In a recent study of 56 teeth of two dif­ pulp chamber. The deposition of this form of dentin ferent age groups (18 to 25 years versus older than is a physiologic process, and it can be measured 60 years) with 20 days of bacterial incubation in the indirectly as a function of chamber size using various canals, the results suggested that bacterial penetra­ radiographic methods and films. tion inside the tubules occurred to a lesser extent in These studies confirm that radiographs can be the older patients.172 utilized to detect changes occurring in root canal These results are in accordance with the findings spaces in aging individuals. The importance of this of another study of teeth from four different age effort lies in the clinical application of the findings to groups (younger than 30 years, 30 to 45 years, 46 to tooth retention. It appears that treatment modalities 60 years, and older than 60 years) involving dye pen­ currently in place were developed for use in gener­ etration. After 1 and 30 days of dye penetration, sig­ ally young patient populations using approaches nificant differences were found among teeth of the that may not work for the elderly individual. Thus, different age groups, but only in the apical third. The without interventions at an earlier time, the elderly dye-penetration areas systematically decreased with may require complicated, lengthy endodontic sur­ increasing age and from coronal to apical. Although gical procedures or risk losing teeth. In addition, dye-penetration techniques are controversial, these elderly patients may have serious health problems results tend to confirm the age dependence of den­ that make such procedures risky. tin permeability.173 However, if the reduction in size of the tubules is a Effects of pulp capping procedures in limiting factor to bacterial penetration, it also appears that the penetration and efficiency of disinfectant aging tissue solutions are more limited in teeth of older patients than in teeth of younger ones and that biofilm is more The success of pulp capping procedures depends difficult to eliminate from mature teeth.174 on many factors, including the size of the exposure, extent of bacterial infection, materials and tech­ niques employed, and preparation of a clean and Radiographic signs of aging disinfected surface (see chapter 13). Most clinical investigations on pulp capping are Radiographs have been used in the diagnosis of conducted in young to early middle-aged patients; pulpal and periradicular diseases. They are equally comparatively few studies include older patients important in defining the anatomy of root canal sys­ who qualify as aging to elderly individuals. One tems and the presence of calcification that may influ­ study evaluated the success of pulp capping in 149 ence treatment options (see Fig 18-11 ). Although patients (aged 8 to 74 years) with a minimum 5-year

441 www.shayanNemodar.com Aging and the Pulp follow-up.177 The authors found an overall success I References rate of 87 .3% and reported that patient age at the time of pulp capping was not a factor in success or failure of the treatment. Another study evaluated the 1. Goodis HE, Rossall JC, Kahn AJ. Endodontic status in older U.S. adults. Report of a survey. J Am Dent Assoc 2001; 132: 1525-1530. 148 16 success of pulp capping in patients (aged to 2. Skaar DD, Hardie NA. Demographic factors associated with dental uti­ 67 years) with a 3-year follow-up.178 These authors lization among community dwelling elderly in the United States, 1997. J Public Health Dent 2006;66:67-71. found a similar rate of clinical success (88%) and 3. Shay K, Ship JA. The importance of oral health in the older patient. J Am reported that older patients also had similar suc­ Geriatr Soc 1995;43: 1414-1422. cess after pulp capping. Similar results have been 4. Shay K. The evolving impact of aging America on dental practice. J Contemp Dent Pract 2004;5:101-110. reported by most, but not all, clinical investigations 5. Manski RJ, Macek MD, Moeller JF. Private dental coverage: Who has it and evaluating the efficacy of pulp capping in a broad how does it influence dental visits and expenditures? J Am Dent Assoc range of patient age groups (10 to 70 years).179 2002;133: 1551-1559. 6. Goodman HS, Manski MC, Williams JN, Manski RJ. An analysis of preventive Thus, age as a prognostic factor does not appear dental visits by provider type, 1996. J Am Dent Assoc 2005; 136:221-228. to play a decisive role in success or failure of pulp 7. Moss KL, Beck JD, Mauriello SM, Offenbacher S, White RP Jr. Third molar periodontal pathology and caries in senior adults. J Oral Maxillofac Surg capping procedures. This is probably because pulp 2007;65: 103-188. capping procedures are only performed on teeth 8. Murray PE, Ede-Nichols D, Garcia-Godoy F. Oral health in Florida nursing with a patent, radiographically visible pulp chamber. homes. Int J Dent Hyg 2006;4:198-203. 9. Murray PE, Stanley HR, Matthews JB, Sloan AJ, Smith AJ. Age-related odont­ ometric changes of human teeth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;93:474-482. 10. Rattan SI. Theories of biological aging: Genes, proteins, and free radicals. Future Directions Free Radie Res 2006;40:1230-1238 . I 11. Hayflick L, Moorhead PS. The serial cultivation of human diploid cell strains. Exp Cell Res 1961;25:585-621. 12. Hayflick L. Current theories of biological aging. Fed Proc 1975;34:9-13. 13. Hayflick L. Intracellular determinants of cell aging. Mech Ageing Dev Dramatic demographic changes have led to a rec­ 1984;28:177-185. ognition of the importance of the aging process as 14. Hayflick L. The cell biology of aging. Clin Geriatr Med 1985;1:15-27. 15. Hayflick L. How and why we age. Exp Gerontol 1998;33:639-653. it relates to oral health. More information is essential 16. Rubelj I, Vondracek Z. Stochastic mechanism of cellular aging-Abrupt telo­ if the dental profession is to develop the strategies mere shortening as a model for stochastic nature of cellular aging. J Theor necessary to diagnose and treat an increasingly Biol 1999; 197:425-438. 17. Hayflick L. Biological aging is no longer an unsolved problem. Ann NY Acad older patient population. As humans live longer, tis­ Sci 2007;1100:1-13. sues undergo age-dependent and age-independent 18. ltahana K, Campisi J, Dimri GP. Mechanisms of cellular senescence in human changes. This necessitates an understanding of the and mouse cells. Biogerontology 2004;5:1-10. 19. Kregel KC, Zhang HJ. An integrated view of oxidative stress in aging: Basic aging process and its impact on local conditions mechanisms, functional effects, and pathological considerations. Am J (caries) and systemic conditions such as diabetes or Physiol Regul lntegr Comp Physiol 2007;292:R18-R36. 20. Ryley J, Pereira-Smith OM. Microfluidics device for single cell gene expres­ coronary artery disease (see chapter 20). sion analysis in Saccharomyces cerevisiae. Yeast 2006;23: 1065-1073. Too often we face situations that remind us of the 21. Greider CW. Telomeres and senescence: The history, the experiment, the time when teeth were removed for no better reason future. Curr Biol 1998;8:R178-R 181. 22. Wei YH, Ma YS, Lee HC, Lee CF, Lu CY. Mitochondrial theory of aging than no one knew that they could be retained. Not matures-Roles of mtDNA mutation and oxidative stress in human aging. too many years ago, the dental pulp under "stress" Zhonghua Yi Xue Za Zhi (Taipei) 2001;64:259-270. signaled the demise of the tooth, leading to its 23. Lee HC, Wei YH. Oxidative stress, mitochondrial DNA mutation, and apopto­ sis in aging. Exp Biol Med (Maywood) 2007;232:592-606. removal and replacement (or not) with a prosthetic 24. Sozou PD, Kirkwood TB. A stochastic model of cell replicative senescence appliance. More recently, improved instrumentation based on telomere shortening, oxidative stress, and somatic mutations in nuclear and mitochondrial DNA. J Theor Biol 2001;213:573-586. and clinical procedures have allowed treatment of 25. Harman D. Aging: A theory based on free radical and radiation chemistry. J such clinically compromised teeth, leading to their Gerontol 1956; 11:298 -300. retention as useful and pain-free contributors to the 26. Weinert BT, Timiras PS. Invited review: Theories of aging. J Appl Physiol 2003;95: 1706-1716. masticatory process. The continued development of 27. Wallace DC. A mitochondrial paradigm of metabolic and degenerative dis­ basic and clinical science procedures and products eases, aging, and cancer: A dawn for evolutionary medicine. Annu Rev Genet based on aging mechanisms and their impact on the 2005;39:359-407. 28. Hamilton ML, Van Remmen H, Drake JA, et al. Does oxidative damage to dental pulp are likely to lead to more effective oral DNA increase with age? Proc Natl Acad Sci USA 2001;98:10469-10474. care of the aging patient. 29. Hutter E, Unterluggauer H, Uberall F, Schramek H, Jansen-Durr P. Replicative senescence of human fibroblasts: The role of Ras-dependent signaling and oxidative stress. Exp Gerontol 2002;37: 1165-1174.

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Anat Embryol (Berl) 1986; 175:189- 198. 47. Kim S. Molecular biology of aging. Arch Surg 2003;138: 1051-1054. 78. Elfenbaum A. Aging changes in the pulps of sound teeth. Dent Dig 48. Knapowski J, Wieczorowska-Tobis K, Witowski J. Pathophysiology of ageing. 1968;47:513-516. J Physiol Pharmacol 2002;53:135-146. 79. Frohlich E. Geriatric changes in the pulp and the periodontium [in German]. 49. Loft S, Deng XS, Tua J, Wellejus A, S0rensen M, Poulsen HE. Experimental Dtsch Zahnarztl 1970;25:175-183. study of oxidative DNA damage. Free Radie Res 1998;29:525-539. 80. Stanley HR, Ranney RR. Age changes in the human dental pulp. I. The 50. Macieira-Coelho A. Biology of aging. Prag Mal Subcell Biol 2003;30: quantity of collagen. Oral Surg Oral Med Oral Pathol 1962;15: 1396-1404. Ill-VI, 1-189. 81. Nielsen CJ, Bentley JP, Marshall FJ. Age-related changes in reducible cross­ 51. Wollscheid-Lengeling E. Time and aging-Mechanisms and meanings. Sci links of human dental pulp collagen. 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Telomeres and replicative senescence: Is it only length that changes in human dental pulp. J Endod 2009;35:1211-1217. counts? Cancer Lett 2001; 168: 111-116. 87. Murray PE, About I, Lumley PJ, Franquin JC, Remusat M, Smith AJ. Human 56. Karlseder J, Smogorzewska A, de Lange T. Senescence induced by altered odontoblast cell numbers after dental injury. J Dent 2000;28:277-285. telomere state, not telomere loss. Science 2002;295(5564):2446-2449. 88. Ranly DM, Thomas HF, Chen J, MacDougall M. Osteocalcin expression 57. Marcotte R, Wang E. Replicative senescence revisited. J Gerontol A Biol Sci in young and aged dental pulps as determined by RT-PCR. J Endod Med Sci 2002;57:B257-B269. 1997;23:374-377. 58. Bekaert S, Derradji H, Baatout S. Telomere biology in mammalian germ cells 89. Hillmann G, Geurtsen W. Light-microscopical investigation of the distribu­ and during development. Dev Biol 2004;274: 15-30. tion of extracellular matrix molecules and calcifications in human dental 59. 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92. Thewlis J. The structure of teeth as shown by x-ray examination. Arch Oral 117. Bernick S. Age changes in the blood supply to human teeth. J Dent Res Biol 1940;7:195-205. 1967;46:544-550. 93. Simon S, Smith AJ, Lumley PJ, et al. Molecular characterization of young 118. Ma Q, Hu X, Yu P. Studies on aging enzyme activities of the human den­ and mature odontoblasts. Bone 2009;45:693-703. tal pulp blood vessels [in Chinese]. Zhonghua Kou Qiang Yi Xue Za Zhi 94. Larmas M. Pre-odontoblasts, odontoblasts, or "odontocytes." J Dent Res 1997;32:81-83. 2008;87:1 98. 119. Espina Al, Castellanos AV, Fereira JL. Age-related changes in blood capillary 95. Couve E, Schmachtenberg 0. Autophagic activity and aging in human endothelium of human dental pulp: An ultrastructural study. Int Endod odontoblasts. J Dent Res 2011;90:523-528. J 2003;36:395-403. 96. Schroeder HE, Krey G, Preisig E. Age-related changes of the pulpal dentin 120. Osterberg T, Era P, Gause-Nilsson I, Steen B. 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Demonstration and semi-quanti­ inflammation in rat molars analysed by quantitative immunocytochemistry. fication of mtDNA from human dentine and its relation to age. Int J Legal Arch Oral Biol 1992;37:901-912. Med 1999;112:98-100. 131. Sarram S, Lee KF, Byers MR. Dental innervation and CGRP in adult 106. Takasaki T, Tsuji A, Ikeda N, Ohishi M. Age estimation in dental pulp DNA p75-deficient mice. J Comp Neurol 1997;385:297-308. based on human telomere shortening. Int J Legal Med 2003;11 7:232-234. 132. Riley JL 3rd, Gilbert GH, Heft MW. Health care utilization by older adults in 107. Shiba H, Nakanishi K, Rashid F, et al. Proliferative ability and alkaline phos­ response to painful orofacial symptoms. Pain 1999;81 :67-75. phatase activity with in vivo cellular aging in human pulp cells. J Endod 133. Morse DR. Age-related changes of the dental pulp complex and their 2003;29:9-11. relationship to systemic aging. Oral Surg Oral Med Oral Pathol 1991;72: 108. 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445 www.shayanNemodar.com www.shayanNemodar.com Differential Diagnosis of Toothache: Odontogenic Versus Nonodontogenic Pain

Jeffrey P. Okeson, DMD

Epidemiologic studies indicate that toothache rep­ gies. Major references on this topic are available to resents the most prevalent form of orofacial pain, the interested reader.4-6 The primary purpose of this with about 12% to 14% of the population reporting a chapter is not to provide a broad overview of this history of a toothache over a 6-month period.1-3 topic but instead to focus on strategies for devel­ Although these studies indicate that dental pain oping a differential diagnosis of odontogenic and is the most commonly reported form of orofacial nonodontogenic dental pain. Other sources should pain, it should be recognized that perception of be reviewed for an extensive discussion of etiology, a toothache may not always have its origin in the diagnosis, and management of various nonodonto­ dental structures. Thus, pain management begins genic pain disorders.7-16 with an accurate differential diagnosis of the ori­ gin of the pain. This is a critical first step in pain management because effective treatment must be directed toward removing or controlling the underly­ I Referral of Pain ing cause. Understanding the basic science of pain mecha­ nisms and the therapeutics of pain management is Because dental pain is such a common cause of a major theme in pulpal biology. Accordingly, this orofacial pain, the clinician can be easily drawn to an text includes detailed reviews of common etiologic odontogenic diagnosis. This is especially true when factors (chapter 10), inflammatory responses in pulp the patient convincingly reports that the pain is felt (chapters 7, 8, and 11) and periradicular tissue (chap­ in a particular tooth. It is a frustrating experience ter 12), the neuroanatomy and neurophysiology of for both the patient and the clinician when tooth­ dental pulp (chapter 7), pain mechanisms in pulp tis­ ache continues long after sound dental treatment sue and the brain (chapter 8), and strategies for pain has been completed. It is not uncommon to hear management (chapter 9). This chapter contributes patients report a history of multiple endodontic pro­ to that foundation of knowledge by focusing on the cedures followed by an extraction, without reduction differential diagnosis of odontogenic and nonodon­ of pain. This type of experience is quite humbling togenic dental pain. to the clinician who is expected to be successful in In recent years, there has been significant inter­ managing various types of dental pain. est in pain research, leading to the development of The clinician must be aware that sometimes pain new theories, diagnostic tests, and treatment strate- felt in the teeth does not originate from the den-

447 www.shayanNemodar.com Differential Diagnosis of Toothache: Odontogenic Versus Nonodontogenic Pain

100 _..._ Referred pain c 0 _No referral "" .. 80 :; Q, 0 Q, 60 'l; 40 .., .. :; E 20 " u 0 0 2 3 4 5 6 7 8 9 10 Pain intensity

Fig 19-1 Convergence of afferent fibers from dental pulp on the same projec­ Fig 19-2 Relationship of pain referral to pain intensity in 400 patients report­ tion neuron in the trigeminal nuclear complex that receives afferent input from ing odontogenic pain (posterior teeth only). Pain intensity was measured on

the masseter muscle. (Reprinted from Hargreaves and Keiser" with permission.) a 0 to 10 integer scale (0 = no pain, 10 = extreme pain). Referred pain was determined by how patients marked areas of pain perception on a mannequin. (Modified from Falace et al" with permission.)

tal structures. In other words, the site at which the neurons, lowering their thresholds.20•21 This phenom­ patient perceives the pain (the tooth) is different from enon, known as central sensitization,22-26 is described the source of the pain. These types of pain are broad­ in further detail in chapter 8. ly called referred pains and are relatively common The hypothesis of convergence has important in the face and oral structures. When a referred pain clinical implications because it explains how the site is felt in a tooth, it is classified as a nonodontogenic of pain perception by the patient can be different toothache. Nonodontogenic toothaches can pose from the location of the source or origin of nocicep­ significant diagnostic challenges to the clinician. tor activation. In the example illustrated in Fig 19-1, the tooth is perceived as the site of pain perception but the source of nociception is actually the masse­ Theory of convergence ter muscle. It is important for the clinician to understand There are several proposed mechanisms that attempt that any source of deep pain input can lead to pain to explain the nonodontogenic toothache. The most referral; in the head and neck, this referral may be common is pain referral. Although several mecha­ felt in the teeth. It is equally important to realize nisms for referred pain have been proposed (see that pain from pulpal nociceptors can be referred to chapter 8), a widely accepted hypothesis is conver­ other craniofacial structures, such as the preauricular gence 17 (Fig 19-1 ). The convergence hypothesis pro­ region.27·28 It is not uncommon for a patient expe­ poses that certain afferent sensory neurons have riencing significant pulpal pain to report that the peripheral terminals that innervate different tissues pain is felt in a large portion of the areas innervated while their central terminals converge on the same by the mandibular and maxillary divisions of the tri­ second-order projection neuron located in the tri­ geminal nerve. geminal nuclear complex. This hypothesis is sup­ Other studies have demonstrated that, as pain ported by strong experimental data that indicate intensity increases, the incidence of pain referral to that afferent neurons from multiple peripheral tissues other regions also increases. For example, a study indeed have central terminals that converge on the of 400 patients with odontogenic pain indicated same trigeminal projection neuron, which receives that its intensity, but not its duration or quality, was sensory input from dental pulpal neurons18 (see Fig significantly associated with pain referral to other 8-17). In fact, it has been estimated that about 50% of craniofacial structures29 (Fig 19-2). In this study, about all pulpal neurons converge with other neurons on the 90% of all patients reporting moderate to severe same trigeminal projection neurons.19 odontogenic pain (5 or more on a scale of 0 to 10) These heterotopic pains are further enhanced also reported pain referred to nearby craniofacial by the fact that the constant barrage of nocicep­ regions. Thus, as pain intensity increases, there is an tive input from deep structures alters the central increased likelihood that the patient will report pain

448 www.shayanNemodar.com Referral of Pain

Rules to exclude primary Box 19-1 (odontogenic) and confirm referred (nonodontogenic) pain

1. Local stimulation of the site of pain does not increase the pain. Maxillary 2. Local stimulation of the source of pain increases the pain at both the source and the site of pain. 3. Local anesthetic blocking of the site of pain does not decrease the pain. 4. Local anesthetic blocking of the source of pain decreases the pain at both the source and the site of pain.

Mandibular

Left Right

Fig 19-3 Extraoral referral patterns of pain originating from maxillary right (n

= 27), mandibular right (n = 31 ), maxillary left (n = 38), and mandibular left

(n = 47) first molars. The dark blue shading indicates the most frequent areas of pain referral; the light blue shading indicates less frequent areas of referral. Referred pain does not generally cross the midline. (Modified from Falace et al29 with permission.)

in associated structures. The most common areas of 1. Local stimulation of the site of pain does not extraoral pain referred from first molar odontogenic increase the pain pain29 are shown in Fig 19-3. In summary, it is impor­ If the toothache is the primary source of pain, then tant to realize that craniofacial pain originating from provocation of the suspected toothache should nondental structures can refer pain to teeth, and, increase the pain. Although thermal allodynia of the conversely, pain originating from pulpal nociceptors suspect tooth is a hallmark feature of pulpitis (odds can refer pain to other craniofacial structures. ratio of 9.0 versus acute periradicular periodontitis) When a patient reports to the dental office with while mechanical allodynia is a hallmark feature of a complaint of pain, it is the primary responsibility periradicular pain (odds ratio of 6.9 versus pulpitis), of the clinician to find the source of the pain and these provocative stimuli should still elicit pain when direct treatment toward eliminating it. This is the applied to the suspect tooth.32 This is not the case only way the patient's pain can be eliminated. It is with a nonodontogenic toothache. Because the per­ therefore imperative that the clinician appreciate the ceived source of the toothache is not the same as wide variety of presentations of orofacial pain. The the site of nociceptor activation, local provocation clinician must have the diagnostic skills to be able of the toothache (the site) will not change the pain. to differentiate the site of pain from the source of A lack of response to local provocation should be a pain. Patients will quickly report the location in which key that makes the clinician suspect a nonodonto­ they feel the pain but have no understanding that genic toothache. this may not be the actual source of the pain. Clearly, referred pain can pose a significant problem for the 2. Local stimulation of the source of pain increases clinician. the pain at both the source and the site of pain When a toothache is suspected to be a site of referred pain, sometimes the true source of nocicep­ Differentiation between site of pain and tive activation can be found relatively easily, such as source of pain with myofascial trigger point pain. Once a trigger point is identified, it should be stimulated and the There are four clinical rules that can help the clini­ patient asked if he or she feels the pain anywhere cian differentiate a site of pain from a source of pain else. Often the patient will report pain not only in the (Box 19-1 and Fig 19-4). The proper use of local area of palpation (the trigger point) but also radiat­ anesthesia can greatly assist in this task.7•9·29-31 ing to the site of pain, the tooth. This clinical finding

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Fig 19-4 Four important clinical rules No change in pain Increased pain at the tooth that help differentiate odontogenic tooth­ ache from nonodontogenic toothache. (a) Local provocation of the site of pain (a painful tooth) does not increase the !) pain. (b) Local provocation of the source of the pain (a myofascial trigger point in the temporalis muscle) increases the pain not only at the source but also at the site (increasing the tooth pain). (c) Local anesthesia of the site of pain (the painful tooth) does not decrease the pain. (d) a b Local anesthesia of the source of the pain No change in pain Elimination of pain (the temporalis trigger point) decreases the pain not only at the source but also at the site (tooth pain is eliminated). (Reprinted from Okeson' with permission.)

c d

helps confirm that the perceived toothache is actually is "numb." The patient's answer will not provide the due to referred pain; treatment should be directed to needed information because the patient will certain­ the myofascial pain condition and not the tooth. ly feel numb in the tissues that have been anesthe­ As discussed later in this section, some sources tized, that is, the tooth and adjacent soft tissues. The of pain that produce nonodontogenic toothache are proper question is, "I know you are numb, but does not easily located or palpated, making this rule dif­ it still hurt?" This is a different question and directed ficult to clinically demonstrate. Instead, the history to the information needed to make the diagnosis. should be used to gather information. Questioning If the patient says, "I am very numb, but there is no the patient regarding conditions that exacerbate change in my pain," then the clinician has reason­ the toothache can be very valuable in identifying the able evidence that the anesthetized tissues are not true source of pain. In addition, understanding the the structures that have to be treated to resolve the characteristics of the pain (quality, duration, onset, pain. The use of a local anesthetic is basic to differ­ etc) may also give the clinician insight as to the etiol­ entiating dental pain and should be used whenever ogy of the pain source. the source of pain is questionable. Patients with severe pain in mandibular molars 3. Local anesthetic blocking of the site of pain does may not experience complete anesthesia following not decrease the pain nerve block injection. Indeed, in one clinical trial, The injection of a local anesthetic is a very valuable an inferior alveolar nerve block produced successful diagnostic tool in identifying the source of toothache. anesthesia in only about 38% of patients with irre­ When a toothache is the primary source of pain, versible pulpitis of the mandibular molars.33 The cli­ anesthetizing the tooth will immediately reduce or nician may be misled to believe that the incomplete eliminate the pain. When this occurs, the dentist must response to anesthetic injection indicates that the identify the local cause of nociception (ie, pulpal, patient's pain is referred pain. The success rate of periradicular, periodontal, or mucosal) and provide anesthetic for irreversible pulpitis of the mandibular the appropriate dental treatment. molars improves to 88% when the inferior alveolar However, when a local anesthetic fails to elimi­ nerve block is combined with intraosseous supple­ nate the toothache, referred pain should be suspect­ mental injection.33 Thus, the combined injections in ed. The clinician has to be careful, however, as to these cases provide a reasonably good test of pain how he or she asks the patient about the pain after referral when patients continue to perceive pain anesthesia. Often the clinician will ask if the patient even while the adjacent soft tissues are numb.

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4. Local anesthetic blocking of the source of pain Common �eatures of odontogenic Box 19_2 decreases the pain at both the source and the site I dental pain of pain • Presence of etiologic factors for an odontogenic origin of When anesthetizing the tooth does not alter the pain (eg, caries, leakage of restorations, trauma, fracture) toothache, the true source of the pain has to be •Ability to reproduce chief complaint during examination • Relief of pain provided by local anesthetic injection identified. When the true source is found (as with • Unilateral pain myofascial trigger points), the source should be • Pain qualities: dull, aching, throbbing anesthetized (trigger point injection) for confirma­ • Localized pain* tion. Anesthesia of the true source will eliminate not • Sensitivity to temperature* • Sensitivity to percussion or digital pressure* only the source of pain but also the site of referred *Diagnosis specific. pain. Therefore, the toothache will be resolved imme­ diately. When this occurs, the clinician has identified the true source of the toothache, and therapy should be directed toward resolving this source. Although the use of local anesthetic with these exactly the same findings. Indeed, pain of pulpal rules can be very helpful, false-positive results are origin is often characterized by difficulty in localizing possible. Thus, the local anesthetic test must be the source of pain. In contrast, pain originating from considered in the context of the other findings in acutely inflamed periradicular tissue is generally much each case. The local anesthetic test provides only easier for the patient to localize.7 Thus, common fea­ an approximate localization because multiple teeth tures does not imply ubiquitous features, and several are anesthetized even when injections are given by of those clinical findings listed in Box 19-2 are specific intraosseous or intraligamentary routes.34•35 Similarly, to certain diagnoses. For example, discriminant analy­ if a clinician cannot reproduce the patient's chief sis of 74 patients with orofacial pain indicated that complaint (eg, lingering pain to cold stimulus in a pain caused by pulpal pathosis is significantly associ­ patient reporting thermal sensitivity}, then alterna­ ated with thermal allodynia (ie, temperature sensitiv­ tive origins of the pain should be considered, includ­ ity; odds ratio of 9.0 versus apical periodontitis; P < ing even teeth previously provided with nonsurgical .001), whereas pain caused by apical periodontitis is root canal treatment.36 significantly associated with mechanical allodynia (ie, digital or percussion sensitivity; odds ratio of 6.9 ver­ sus pulpitis; P < .01).32

Odontogenic Toothache (Pulpal and Periradicular Pain) I Nonodontogenic Toothache

Fortunately for the dentist, most patients report­ ing dental pain have symptoms that are caused by Although nonodontogenic toothache is less common dental structures (see chapters 7 and 8). Examples of than odontogenic toothache, it is certainly common odontogenic sources of toothache include reversible enough to be a clinical problem. The clinician must pulpitis, irreversible pulpitis, acute apical periodonti­ always remember that effective management of the tis, and acute apical abscess.15 However, the clinician pain can only begin once the true source of pain should always consider other potential sources of has been located. Many structures of the face and pain, especially when a local etiology is not obvious, neck can refer pain to the teeth. The clinician must to develop an accurate differential diagnosis for all understand these structures and the clinical charac­ patients.13,32,37 teristics of each because this knowledge will assist in Common clinical features of odontogenic dental making the correct diagnosis. Some of the common pain11·13-15·37 are listed in Box 19-2 and are more thor­ clinical findings for nonodontogenic toothache are oughly discussed in earlier chapters of this textbook. listed in Box 19-3. More specific clinical symptoms are Although this list provides a useful summary of char­ described for each type of nonodontogenic tooth­ acteristic features of odontogenic pain, the skilled ache in the following sections. clinician will realize that not all patients present with

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Nonodontogenic toothache of _3 Common features of 8 ox 19 I nonodontogenic dental pain myofascial origin • Absence of apparent etiologic factors for odontogenic pain (eg, no caries, leaky restorations, trauma, or fracture) • No consistent relief of pain provided by local anesthetic Etiology injection Myofascial pain is a regional myogenous pain condi­ • Bilateral pain or multiple painful teeth tion characterized by local areas of firm, hypersensi­ • Chronic pain that is not responsive to dental treatment

• Pain qualities: burning, electric shooting, stabbing, tive bands of muscle tissue known as trigger points. It dull ache* is a muscle pain disorder diagnosed in more than 50% • Pain that occurs with a headache* of the patients reporting to a university pain center.40 • Increased pain associated with palpation of trigger points or muscles* Myofascial pain was first described by Tr avell • Increased pain associated with emotional stress, physical and Rinzler41 in 1952. This pain condition arises from exercise, head position, etc* hypersensitive areas in muscles called trigger points. *Diagnosis specific. These very localized areas in muscle tissues and/ or their tendinous attachments are often felt as taut bands when palpated, which elicits pain. The exact nature of a trigger point is not known.42 It has been suggested43·44 that certain nociceptors in the muscle tissues may become sensitized by algogenic sub­ stances that create a localized zone of hypersensitiv­ There are several classification schemes for cat­ ity.45 There may be a local temperature rise at the site egorizing orofacial pain.7·16•38·39 Although these diag­ of the trigger point, suggesting an increase in meta­ nostic schemes share many similarities, they are not bolic demand and/or increase in blood flow to these identical, and they have not all been validated in tissues.46.47 A trigger point is a very circumscribed large-scale, multicenter studies. Because the goal of region in which relatively few motor units seem to be this chapter is to provide a useful overview of those contracting.48 Because a trigger point has activity in pain disorders that can contribute to nonodonto­ only a select group of motor units, no overall shorten­ genic toothache, a full classification of orofacial pain ing of the muscle results. The unique characteristic is not reviewed. Instead, information is provided of trigger points is that they are a source of constant that will help the clinician identify the orofacial pain deep pain and therefore can produce referred pain to disorder likely to be responsible for the pain referral. a variety of facial structures, including the teeth. Once the clinician understands that pain originating The etiology of myofascial pain is complex. from each orofacial structure will present with dif­ Unfortunately, we lack a complete understanding ferent clinical characteristics, differential diagnosis of this myogenous pain condition. It is therefore becomes possible. difficult to be specific concerning all etiologic fac­ The most common pain conditions to trigger tors. Simons et al47 have described certain local and nonodontogenic toothaches are reviewed in this sec­ systemic factors that seem to be associated, such as tion. They are myofascial toothache, sinus toothache, trauma, hypovitaminosis, poor physical condition­ neurovascular toothache, neuropathic toothache, ing, and fatigue. Other important factors are likely cardiac toothache, somatoform toothache, and tooth­ to be emotional stress and deep pain input. Recent ache of systemic origin. Subcategories of neurovas­ research has pointed toward polymorphisms of a cular and neuropathic toothaches are also described. gene whose protein (catechol-0-methyltransferase) Knowing the pain characteristics for each of these dis­ is involved in catecholamine metabolism,49 and it orders is an essential key to diagnosis. The etiology is possible that at least certain forms of myofascial of each of these sources of nonodontogenic tooth­ pain may have a central etiology, which is reflected ache and the clinical characteristics that will assist in by a peripheral trigger zone rather than caused by a making the diagnosis are discussed. Management peripheral trigger zone. considerations are only briefly mentioned because On the other hand, two studies have been con­ other texts provide a more thorough review of man­ ducted in twins to determine the relative contribu­ agement.4.7 tion of genetic (ie, anatomical or physiologic) versus environmental (ie, learned) factors to masticatory

452 www.shayanNemodar.com Nonodontogenic Toothache

Fig 19-5 Frequency distribution of nonodontogenic dental pain referred to teeth after palpation of selected muscles in a group of 230 patients with temporomandibular dysfunction. Firm pressure was applied for 5 seconds to selected sites, and the patients were instructed to report on palpation-induced referred pain during stimulation. Muscles were palpated by applying sustained firm pressure while sliding the fingers along the length of the muscle. The entire body of the masseter muscle was palpated. The temporal muscle was palpated superior to the zygomatic arch. The lateral pterygoid muscle was palpated by applying the fifth digit along the buccal alveolar ridge just apical to the maxil­ Molars Premolars Anteriors Molars Premolars Anteriors lary molars. The lateral pole and posterior aspect of the temporomandibular Maxillary teeth Mandibular teeth joint (TMJ) were palpated with the mouth open. (Data from Wright. 53)

muscle pain and other temporomandibular dysfunc­ effects. Therefore, when a trigger point is active, a tion symptoms.50·51 The authors reported little to no toothache is commonly felt. Because referred pain is heritability for self-report of any pain. Another study wholly dependent on its original source, palpation of reported no significant genetic influence on the an active trigger point (local stimulation) often increas­ dolorimetric measurement of pressure pain thresh­ es such pain. Although not always present, this charac­ olds in 609 female-female twins.52 Thus, the relative teristic has extremely important diagnostic value. contribution of genetic and environmental factors In the latent state, a trigger point is no longer sen­ on the development of myofascial pain remains an sitive to palpation and therefore does not produce active area of research. referred pain. When trigger points are latent, they can­ not be found by palpation, and the patient does not Clinical characteristics complain of toothache. In this case, the history is the Myofascial pain is often described as a deep, dull, only data that leads the clinician to make the diagno­ aching muscle pain that can be associated with sis of myofascial pain. In some instances, the clinician referred dental pain. Classic studies47 have demon­ should consider asking the patient to return to the strated that three masticatory muscles commonly office when the toothache is present so that the pat­ refer pain to the teeth. These are the superior belly tern of pain referral can be verified and the diagnosis of the masseter (to the maxillary posterior teeth) and confirmed. inferior belly of the masseter (to the mandibular pos­ It is thought that trigger points do not resolve terior teeth), the temporal (to the maxillary anterior without treatment. They may in fact become latent or posterior teeth), and the anterior digastric (to the or dormant, creating temporary relief of the referred mandibular anterior teeth).47 pain. Trigger points may be activated by various fac­ In a series of 230 cases of patients with a diagnosis tors,47 such as increased use of a muscle, strain on the of temporomandibular dysfunction, 85.0% demon­ muscle, emotional stress, or even an upper respira­ strated referred pain with palpation of muscles or tory infection. When trigger points are activated, the trigger points, and 11.6% of these patients had pain toothache returns. This is a common finding among referred to the teeth53 (Fig 19-5). Molars were the patients who complain of regular late afternoon teeth that most frequently received referred pain from toothache following a very trying and stressful day. muscle or trigger point palpation, and the masseter The following are the key clinical characteristics muscles were the most common source. The tempo­ of toothache of myofascial origin: ralis muscle and even the temporomandibular joint

(TMJ) itself also commonly referred pain to the teeth. • The pain is relatively constant, dull, aching, and It is therefore important that the clinician palpate nonpulsatile. these muscles for potential sources of pain referral • The pain is not altered by local stimulation of the (Figs 19-6 to 19-10). tooth.

An interesting clinical feature of a trigger point • Examination reveals the presence of localized, is that it may present in either an active or a latent firm, hypersensitive bands within the muscle tis­ state. In the active state, it produces central excitatory sues (trigger points).

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f

Fig 19-6 (a) Trigger points in the masseter muscle can refer pain to the Fig 19-7 (a) Trigger points in the temporalis muscle can refer pain to the max­ maxillary or mandibular posterior teeth. (b) Palpation of the masseter muscle to illary teeth. (b) Palpation of the temporalis muscle to assess for any pain that assess for any pain that may be referred to the posterior teeth. may be referred to the maxillary teeth.

Fig 19-8 (a) Trigger points in the anterior digastric muscle can refer pain to Fig 19-9 Palpation of the sterno­ Fig 19-10 lntraoral palpation of the mandibular anterior teeth. (b) Palpation of the anterior belly of the digastric cleidomastoid muscle to assess for the medial pterygoid muscle to assess muscle to assess for any pain that may be referred to the mandibular anterior any pain that may be referred to the for any pain that may be referred to teeth. face, TMJ, or teeth. the posterior teeth.

• Other heterotopic pains are often reported (eg, Nonodontogenic toothache of sinus tension-type headache). or nasal mucosal origin • The toothache is increased with function of the involved muscle (trigger points).

• Palpation and stimulation of the trigger points Etiology increase the toothache. Pain arising from the nasal mucosa as the result of

• Confirmed anesthesia of the tooth does not alter viral, bacterial, or allergic rhinitis may be expressed the toothache. as referred pain throughout the maxilla and maxillary

• Local anesthetic injection of the involved muscle teeth in the form of a toothache. It may also display (trigger points) reduces the toothache. autonomic signs that are mistaken for symptoms of maxillary sinusitis. The so-called sinus headache may Management considerations cause management problems because of the associ­ Several treatment modalities have been suggested ated nonodontogenic tooth pain. The nonodonto­ for these patients. A partial list includes identifica­ genic pain is likely to arise from inflammation of the tion and elimination of contributory factors, mild ostium, which compresses a significant concentra­ analgesics, spray and stretch therapy, deep massage, tion of nociceptors and often refers pain to the max­ biofeedback, deep heat, and injection of the trig­ illary teeth.ss ger points. The specific combination of treatments depends on the diagnosis, the patient's responses, Clinical characteristics and the treatment philosophy of the clinician.7·31.47•54 Unlike odontogenic pain, nonodontogenic dental pain evoked by sinusitis is often characterized by pain that is not restricted to a single tooth (ie, pain may include the malar and maxillary alveolar regions), pain that may be partially relieved by a diagnostic intraoral local anesthetic block, pain that increases

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after percussion, and occasional thermal sensitivity lanic acid or trimethoprim-sulfamethoxazole.58 Aller­ to cold.5·9·56•57 Patients may report a sense of pressure gic sinusitis is often treated with antihistamines or or fullness in the infraorbital region over the involved decongestants. sinus. A particularly distinguishing characteristic is Pain in the maxillary sinuses as well as in the max­ the presentation of multiple maxillary posterior teeth illary and mandibular teeth also can be triggered by with percussion sensitivity and a positive response reduced atmospheric pressure. Several case reports to pulpal vitality testing. Reduction of pain after the have described odontogenic and nonodontogenic intranasal application of a 4% lidocaine spray is con­ dental pain in patients during or after airplane flights sidered diagnostic.57 Alternatively, a swab soaked with or scuba diving.59-62 It has been recommended that 5% lidocaine can be placed in the middle meatus for dental treatment, including root canal obturations, 30 seconds for evaluation of pain reduction.8 be completed more than 24 hours prior to exposure Bacteria-induced sinusitis pain is characterized to reduced atmospheric pressure.60 as a severe, throbbing, stabbing pain with a sense There are several additional inflammatory con­ of pressure. More than 70% of cases are caused by ditions that may lead to a misdiagnosis. These Streptococcus pneumoniae or Haemophilus influen­ include pain referred from another tooth (see chap­ zae.58 In cases of moderate to severe sinusitis, a pos­ ter 8), impacted third molars,63 eruption sequestra of itive "head-dip" test is observed (ie, pain increases bone,64 otitis media, and foreign bodies impacted in when the patient lies down or places his or her periodontal tissues during mastication65 or retained head below the knees), and patients may report a under surgical tissue flaps.66 The correct diagnosis purulent nasal discharge. Radiographic imaging of requires careful history taking, clinical examination, the sinuses, particularly a Waters view or computed and interpretation of findings. tomographic scan, may reveal fluid accumulation. Allergy -induced sinusitis tends to be seasonal in Nonodontogenic toothache of colder climates but can occur at any time in temper­ ate climates. The pain is often characterized as a neurovascular origin chronic, dull ache in the maxillary posterior region with a positive percussion test of molars or premo­ Neurovascular pain conditions are unique pain disor­ lars. Interestingly, patients also may report an "itch­ ders only felt in the craniofacial structures. The intra­ ing" sensation in the maxillary teeth. cranial vessels of the brain are primarily innervated by The following are the key clinical characteris­ the trigeminal nerve and thus called the trigeminovas­ tics of nonodontogenic toothache of sinus or nasal cu/ar system. Several pain conditions can arise from mucosal origin: the trigeminovascular structures, two of which have been known to produce pain in the teeth. These are

• The patient reports pressure felt below the eyes. migraine and trigeminal autonomic cephalgia.

• The pain is increased when pressure is applied over the involved sinus. Migraine

• The tooth is sensitive to percussion. Etiology

• The toothache is increased when the patient's The precise etiology of migraine is still debated, head is lowered. but the present evidence suggests that there is a

• The toothache is increased when the patient steps neurologic trigger in the brainstem that initiates a hard on to the heel of the foot (eg, while walking cascade of events that result in neurogenic inflam­ down steps). mation of the cranial vessel, producing the head­

• Local anesthesia of the tooth only partially reduc­ ache.67·68 For this reason, the term neurovascu/ar es the pain or fails to reduce the pain at all. pain is used. Although the exact mechanism and

• The diagnosis is confirmed by appropriate imag­ etiology are unknown, there is certainly evidence of ing of the sinuses (Waters view or computed a genetic susceptibility. Between 50% and 60% of tomographic scan). migraine patients have parents that also experience migraines.69.7° Migraine attacks can be precipitated Management considerations by a variety of triggers, such as stress, dietary fac­ Bacterial sinusitis is often treated with f3-lactamase­ tors, altered sleep patterns, and menstruation.71 resistant antibiotics such as amoxicillin with clavu-

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Clinical characteristics • The episodes of pain may pose a temporal behav­ Migraine is characterized by throbbing, moderate to ior, appearing at similar times during the day, week, severe, often debilitating pain. Sixty percent of the or month. time the headache is unilateral, often reported in the • The toothache is accompanied by photophobia, temple or behind the eye. Migraine can be felt in phonophobia, or osmophobia. the maxillary arch; this form is referred to as midface • The pain is frequently felt in a maxillary canine or migraine. This type can be a diagnostic problem for premolar, and the patient is so convinced of the the dentist because the pain can be felt in the teeth. source of the toothache that dental treatment may The patient will often report photophobia, phono­ be undertaken without hesitation, even when only phobia, and osmophobia and will seek a dark, quiet minor or no dental cause is found. room. The pain is aggravated by routine physical • The pain may actually undergo remission follow­ activity and sometimes even simple head move­ ing dental treatment, although recurrence is char­ ments. acteristic with neurovascular pains. The pain may Nonodontogenic tooth pain evoked by migraine spread to adjacent teeth, opposing teeth, or the can be differentiated from odontogenic pain in that entire face. the former often is characterized by pain that is • The patient reveals a history of other neurovascu­ not restricted to a single tooth (ie, diffuse pain); a lar disorders (migraine). unilateral, dull, throbbing pain quality; pain that is • A trial of an abortive migraine medication (eg, unrelieved by a diagnostic intraoral local anesthetic sumatriptan) reduces the toothache. block; and pain that is not altered by intraoral ther­ mal stimuli.56•57 The diagnosis is often made based Management considerations on reports of a temporal relationship in which the Patients who experience migrainous toothache toothache subsides as the headache symptoms need to understand basic information regarding are reduced. Physical activity (eg, walking a flight their pain condition. They need to know that even of stairs) often increases pain intensity. Migraines though the pain is very severe, it is still benign and are often associated with nausea, emesis, affective not an aggressive tumor such as cancer. A very changes in mood, and sensitivity to light or sound.7·56 important management consideration is to have Migraine occurs more frequently in females, particu­ the patient identify any triggering factors that initi­ larly in those younger than 50 years.72 ate the toothache/migraine attack. Often patients In one case report, a 35-year-old woman report­ have no appreciation of the triggers. Once these ed dental pain in a mandibular canine.57 The pain factors are identified, effort is made to avoid them, persisted after extraction of the tooth. Subsequent so as to reduce the number of episodes of attacks. examination revealed that the pain was associated Factors that relate to diet can usually be quickly with nausea and sensitivity to loud sounds. The controlled. Sometimes environmental factors such as patient denied experiencing an aura during the light, weather changes, and pungent odors may be attacks. Treatment with antimigraine drugs and ces­ more difficult to avoid. Other factors such as fatigue, sation of oral contraceptives reduced the migraine sleep patterns, and stress need to be identified and episodes. addressed appropriately. Nothing is more satisfying The following are the key clinical characteristics to the patient than his or her own ability to control of nonodontogenic toothache of migraine origin: the number of toothache/migraine attacks. This, of course, can only occur with patient education.

• The pain may be spontaneous, variable, and pul­ Pharmacologic management is based on the fre­ satile, characteristics that can simulate pulpal pain. quency of the migraine attacks. Infrequent attacks are

• The pain is usually very intense. managed with abortive medications such as the trip­ • The toothache is characterized by periods of total tans and other serotoninergic agents that block the remission between episodes (like migraine head­ 5-hydroxytryptamine 1 (5HT1) or 5-hydroxytryptamine ache pain). 3 (5HT3) serotoninergic receptors,73-76 such as sumat­

• The toothache may be immediately preceded by riptan (lmitrex, GlaxoSmithKline) or rizatriptan (Maxalt, focal neurologic symptoms (an aura, that is, pho­ Merck). Ergotamine has been largely replaced by topsia, scotoma, or teichopsia). these alternatives because they have a lower inci­ dence of adverse effects. When attacks are more

456 www.shayanNemodar.com Nonodontogenic Toothache

frequent (one or more a week), prophylactic medi­ oral thermal stimuli of the tooth.7·83 Cluster head­ cations are used, such as the r3-adrenergic antago­ aches can be triggered by drugs such as alcohol nists {r3-blockers). Examples of such medications are and cocaine. The pain is generally described as hot, propranolol (lnderal, Wyeth), metoprolol (Lopressor, stabbing, and paroxysmal. The pain attacks often Novartis), timolol (Blocadren, Merck), nadolol (Cor­ occur at the same time of day (especially 4:00 AM to gard, King Pharmaceuticals), and atenolol (Tenormin, 10:00 AM) and often last 30 to 180 minutes.7·57 The AstraZeneca).67·77 Another group of medications used attacks may be associated with rhinorrhea, nasal to prevent migraine attacks are the calcium chan­ congestion, and lacrimation from the involved eye. nel blockers, such as nifedipine (Procardia, Pfizer), The pain is often distributed in the maxillary poste­ verapamil (Calan, Searle/Pfizer; lsoptin, Abbott), and rior teeth, sinus, and retro-orbital regions. nimodipine (Nimotop, Bayer).78 The tricyclic antide­ A related condition is chronic paroxysmal hemi­ pressants have also been useful, especially amitripty­ crania. This disorder has similar pain characteristics line. Clinical trials have also demonstrated efficacy for but, unlike cluster headache, is observed mostly in gabapentin and injection of botulinum toxin.79-B1 females and is completely responsive to indometha­ cin_7.s7 Trigeminal autonomic cephalgia Cluster headaches often evoke nonodontogenic Etiology dental pain. In one study, 43% of subjects with clus­ Tr igeminal autonomic cephalgia is a group of pri­ ter headache were initially treated by a dentist.84 A mary headache disorders that are generally short case report described three patients with nonodon­ in duration but severe in intensity. They are charac­ togenic dental pain resulting from cocaine-induced terized by the presence of clinical signs related to cluster headaches.85 One patient described unilat­ autonomic activity such as lacrimation, conjunctiva! eral maxillary pain in the premolar region that lasted injection, nasal stuffiness, or rhinorrhea. These signs for 30 to 120 minutes after cocaine use. Another are usually present on the same side of the pain. patient reported continued nonodontogenic dental Forehead sweating, facial flushing, and edema may pain in the maxillary molar region. The pain per­ also occur but are less common. Most trigeminal sisted after endodontic treatment and subsequent autonomic cephalgias are felt unilaterally in the extraction of the molar; only later did the patient maxilla, temple, or retro-orbital areas. On occasion, report that the pain started about 1 to 2 hours after this pain may be felt in the teeth. The most common cocaine ingestion. The third patient also reported trigeminal autonomic cephalgia is cluster headache, nonodontogenic dental pain in the maxillary premo­ which is highlighted in this section. lar region after consumption of cocaine. The etiology of cluster headache (Sluder neu­ The following are the key clinical characteristics ralgia) is unknown but has been hypothesized to of toothache of cluster headache origin: be episodic vasodilation that activates perivascular

nociceptors. The term cluster denotes the obser­ • The pain may be spontaneous, variable, and pul­ vation that the pain episodes often last about 6 satile, characteristics that can resemble pulpal to 8 weeks and then are followed by a relative­ pain. ly long pain-free period. Although less common • The pain is very intense and has a sudden onset. than migraines, cluster headaches are often con­ • The toothache is characterized by periods of total sidered to produce more intense pain.7·57·82 Cluster remission between episodes. headaches most often occur in male patients (male­ • The episodes of pain pose a temporal behavior, female ratio: 6: 1) in the age range of 30 to 50 years. appearing at similar times during the day.

• The toothache is reported to occur frequently for Clinical characteristics several weeks (cluster), then resolves without treat­ Nonodontogenic dental pain evoked by cluster ment. headache is distinct from odontogenic pain in that • The pain is frequently felt in a maxillary canine or it is often characterized by pain that is not restricted premolar. to a tooth (ie, pain includes retro-orbital and sinus • The toothache is accompanied by autonomic regions). The pain commonly awakens the patient effects, such as nasal congestion, lacrimation, and from sleep, is unrelieved by a diagnostic intraoral edema of the eyelids and face, which may be mis­ local anesthetic block, and is not altered by intra- taken for sinusitis or dental abscess.

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• The patient reveals a history of other neurovascu­ elinization of the trigeminal nerve root by vascular lar disorders (migraine). compression is a common hypothesis. This theory is supported by studies demonstrating that com­ Management considerations pression of either the sciatic or trigeminal (infraor­ As with migraine, patients who experience cluster bital) nerves in rats produces models of neuropathic headaches need to understand basic information pain.91-93 This demyelinization of the center nerve regarding their pain condition. They need to know root causes a referred pain to be felt in the periph­ that even though the pain is very severe, it is still eral distribution of the involved branch. Therefore, benign and not an aggressive disease. Probably one nonodontogenic tooth pain can be a common part of the most important aspects of education is hav­ of the patient's complaint. ing the patient identify any triggering factors that initiate the attacks.85 Often patients may have no Clinical characteristics. The clinical presentation of understanding of triggers. If the patient can identify a neuralgic toothache is a severe, shooting, electric­ a trigger, then proper avoidance can be instituted. like pain that lasts only a few seconds.5.7.10 The pain Because the attack usually occurs shortly after the is not always restricted to a tooth but often affects trigger, it may be easy for the patient to recognize a broader area. The pain is not altered by intraoral the trigger. thermal stimuli. The most common branch of the Pharmacologic management of cluster headache trigeminal nerve involved is the mandibular branch, is often difficult and not predictable. Patients with followed by the maxillary branch. The pain is often cluster headache have been treated with oxygen severe, and patients report the pain as being the therapy, sumatriptan, prednisone, gabapentin, and most intense they have ever experienced. Often the calcium channel blockers.7·BMlB Ergotamine has been patient is able to trace the pain radiating down the largely replaced by these alternatives because of the distribution of the nerve to the tooth. lower incidence of adverse effects. With trigeminal neuralgia there is often a trig­ ger zone that, when lightly stimulated, provokes the severe paroxysmal pain. Typically, this zone is the lip, Nonodontogenic toothache of chin, or even the tongue. The presence of this char­ neuropathic origin acteristic helps to establish the diagnosis. Anesthetic blocking of the trigger zone will completely elimi­ Neuropathic pain has been defined by the Interna­ nate the toothache and paroxysmal episodes during tional Association for the Study of Pain as pain "initi­ the period of anesthesia. ated or caused by a primary lesion or dysfunction in On occasion, a tooth can represent the trigger the nervous system. "89 Neuropathic pain has its etiol­ zone, posing a great diagnostic challenge for the ogy in the neural tissue itself and not in the structures clinician. Patients with trigeminal neuralgia frequent­ that it innervates.90 Some neuropathic pains present ly receive endodontic treatment for their dental as episodic pain conditions and some are more con­ pain.94·95 Additional case reports also provide exam­ tinuous. To othache of neuropathic origin can likewise ples of the opposite diagnostic problem: Patients present as either an episodic or continuous pain. with odontogenic dental pain may be diagnosed as having trigeminal neuralgia.96 In both types of mis­ Episodic neuropathic toothache diagnosis, the lack of response to treatment is a key Episodic neuropathic pain is characterized by sud­ factor in prompting reassessment of the differential den volleys of electric-like pain referred to as neu­ diagnosis. ralgia. When this type of paroxysmal pain is felt in a In some patients, trigeminal neuralgia initial­ tooth, it can pose a significant diagnostic challenge ly presents with different clinical characteristics. to the clinician. Trigeminal neuralgia is the most Instead of paroxysmal pain, the pain is an aching common episodic neuropathic pain felt in teeth. pain in the sinus region and teeth with a duration of minutes to several hours. This condition is known Nonodontogenic toothache associated with as pre-trigeminal neura/gia.10.97-99 It is thought that trigeminal neuralgia these patients will subsequently develop trigemi­ Etiology. The etiology of trigeminal neuralgia (also nal neuralgia.98·99 The clinical presentation of pre­ known as tic dou/oureux) is unclear; however, demy- trigeminal neuralgia can be a significant diagnostic

458 www.shayanNemodar.com Nonodontogenic Toothache

problem. Often the diagnosis only becomes clear cal procedures such as percutaneous rhizotomy or once the patient starts to develop the more distinct nerve decompression are considered in refractory features of trigeminal neuralgia (paroxysmal pain). cases. 5,7, 102-104 Patients with trigeminal or pre-trigeminal neural­ gia commonly report nonodontogenic dental pain. Nonodontogenic toothache associated with In one series of 41 patients with trigeminal neuralgia glossopharyngeal neuralgia and 19 patients with pre-trigeminal neuralgia, a total Etiology. The etiology of glossopharyngeal neural­ of 61% of patients reported an initial dental pain.10 In gia is unknown but may involve vascular compres­ another series of cases, 29% of 24 patients reported sion of the ninth cranial nerve.9·56 Accordingly, some dental pain as a component of their pre-trigeminal investigators have suggested that glossopharyngeal neuralgia symptoms.99 neuralgia and trigeminal neuralgia have similar eti­ The following are the key clinical characteristics ologies (vascular compression) involving different of episodic neuropathic toothache associated with cranial nerves. Glossopharyngeal neuralgia is only trigeminal neuralgia: about one-tenth as prevalent as trigeminal neural­ gia.56,82

• The pain is a severe, unilateral, lancinating, shock­ like (paroxysmal) pain felt in a tooth. Clinical characteristics. Glossopharyngeal neuralgia

• The pain episodes are brief, lasting only 5 to 10 is similar to trigeminal neuralgia in that both disor­ seconds. ders are characterized by episodic pain; however,

• No pain between episodes is reported. patients with glossopharyngeal neuralgia report less

• The pain is provoked by relatively innocuous tooth pain. The differential diagnosis between non­ peripheral stimulation of a trigger zone. The trig­ odontogenic dental pain evoked by glossopharyn­ ger zone is commonly an extraoral site such as the geal neuralgia and odontogenic pain often includes lip or chin but may be the tooth. the quality and duration of the pain (the former

• Very localized anesthesia of the tooth (interliga­ involves severe shocklike pain that lasts only a few mentous injection) will not reduce the pain unless seconds).7·9·10·100 The pain is often elicited by swallow­ it is also the trigger zone. ing; however, it may also be elicited by chewing or

• A local anesthetic injection at the trigger zone (or talking. The distribution of pain includes the poste­ a nerve block) will eliminate the episodes of par­ rior mandible, oropharynx, tonsillar fossa, and ear.9·82 oxysmal pain and toothache during the period of Other distinguishing features include pain that is anesthesia. unrelieved by a diagnostic intraoral local anesthetic block (unless the trigger point is in the field of anes­ Management considerations. About 2% of parox­ thesia) and pain that is not altered by intraoral ther­ ysmal neuralgias are caused by central pathologic mal stimuli.7·9·101 lesions. Therefore, referral for a neurologic consulta­ The following are the key clinical characteristics tion should be considered, especially if any neurolog­ of episodic neuropathic toothache associated with ic deficit is noted. Several treatment modalities have glossopharyngeal neuralgia: been recommended for patients with trigeminal neu­

ralgia. Ty pically, pharmacologic management is the • The pain is a mild to intense, unilateral, lacerating, first course of treatment. Medications include car­ shocklike (paroxysmal) pain felt in the throat, ear, bamazepine (Tegretol, Novartis), gabapentin (Neu­ jaw, and tooth region.

rontin, Pfizer), pregabalin (Lyrica, Pfizer), baclofen • The pain episodes are brief, lasting only 5 to 10 (Lioresal, Novartis), oxcarbazepine (Trileptal, Novar­ seconds.

tis), topiramate (Topamax, Ortho-McNeil), lamotrig­ • The pain is provoked by swallowing, chewing, or ine (Lamictal, GlaxoSmithKline), and valproic acid talking.

(Depakene, Abbott).7·95·100 Local anesthetic injec­ • There are pain-free periods between the episodes tion into the area of the trigger zone often relieves of pain.

pain during the period of anesthesia. In a series of • Inferior alveolar nerve block does not change the 24 cases, intraoral administration of capsaicin to pain condition. the mucosa resulted in complete or partial relief of pain in approximately 63% of patients.101 Surgi-

459 www.shayanNemodar.com DifferentialDiagnosis of Toothache: Odontogenic Versus Nonodontogenic Pain

Management considerations. Treatment for glosso­ matory process. Its temporal behavior is less dra­ pharyngeal neuralgia includes the same medications matic than that of other neuropathic pains. and protocol used for trigeminal neuralgia (previ­ The clinical symptoms of neuritis depend on ously listed). Resistant cases have been treated with which fibers are affected. Neuritis may present with surgical decompression.82 other sensory alterations, such as hyperesthesia (increased sensitivity to stimulation), hypoesthesia Continuous neuropathic toothache (diminished sensitivity to stimulation), paresthesia Continuous neuropathic pains are pain disorders (abnormal sensation), dysesthesia (an unpleasant, that have their origin in neural structures and are abnormal sensation), and anesthesia (absence of all expressed as constant, ongoing, and unremitting sensation). The key usually is to recognize accom­ pain. The pains will often vary in intensity, but there panying neurologic signs that involve other teeth or are no periods of total remission. Continuous neuro­ nearby structures served by the same nerve. If motor pathic pains can be felt in teeth. There are two types efferent fibers are present in the nerve trunk and are to be considered: neuritic and deafferentation. also affected, muscular signs become evident; these include muscular tic, weakness, or paralysis. If auto­ Nonodontogenic toothache of neuritic origin nomic fibers are present, various autonomic effects (herpes zoster) become clinically evident. When the inflammatory Etiology. Neuritic pain,105-107 sometimes referred to process occurs within a bony canal, the inflammatory as neuritic neuralgia, occurs as the result of altera­ exudate may elicit compression effects. tion of the afferent fibers in a nerve trunk. It is felt as The symptom complex therefore depends on the referred heterotopic pain in the peripheral distribu­ types of fibers affected, the degree of change, the tion of the affected nerve. It is assumed that the eti­ peripheral distribution of the affected fibers, and ology is inflammation arising from traumatic, bacteri­ the state of the inflammatory process. A knowledge­ al, viral, or toxic causes. The process alters the fibers able examiner can utilize these clinical symptoms that mediate pricking and burning pain and elevates to locate the site of inflammation. The relationship the threshold for pricking pain but lowers it for between the clinical symptoms and inflammatory burning pain.105 An example of a bacteria-induced process is strictly anatomical. The effects are directly neuritis is an acute maxillary sinusitis affecting the the result of peripheral fiber involvement and do not superior dental plexus just below the sinus floor. represent central mechanisms. This results in nonodontogenic pain in the maxillary The following are the key clinical characteristics anterior tooth. A similar toothache in the mandibular of toothache of neuritic origin: teeth may occur as an expression of neuritis of the inferior alveolar nerve from direct trauma or dental • The pain is a persistent, nonpulsatile, often burn­ sepsis. ing pain felt in a tooth.

A herpes zoster infection is an example of a viral • The toothache is accompanied by other neuro­ neuritis. Herpes zoster has been reported to pro­ logic symptoms (eg, paresthesia, dysesthesia, or duce nonodontogenic dental pain preceding the anesthesia). eruption of vesicles. These case reports are mixed, • The patient may report that other teeth feel with some reporting pulpalgia-like symptoms and "dead" or "strange." others reporting necrosis with the presence of peri­ • The associated gingival tissue may be affected. radicular lesions.100-111 • The onset of the toothache followed an infection or trauma (eg, sinusitis, viral infection, or trauma). Clinical characteristics. Neuritic toothache is char­ acterized by a burning quality that may be accom­ Management considerations. The management of panied by other symptoms of neuropathic pain, neuritic toothache begins with understanding the such as an intense, stimulating, precisely localizable etiology of the inflammation. When a bacterial source pain that is accurately related in location to the site is suspected, antibiotics are indicated. Other treat­ of inflammation and/or projecting to the peripheral ments needed to eliminate the infection should be distribution of the affected nerve. Although variable undertaken. When a viral infection is suspected, anti­ in degree, neuritic pain has a strange constancy that viral medications such as acyclovir, valacyclovir, or relates to the incidence and resolution of the inflam- famciclovir can be helpful.112·113 When no obvious

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infection exists, administration of steroids should be In many of these cases, the lack of response to treat­ considered.114·115 Steroids can reduce swelling of the ment was a key factor in prompting reassessment nerve tissue, which may be extremely important when of the differential diagnosis.54 In one case report, neuritis affects a nerve that exits a cranial foramen. the lack of an effect of a local anesthetic injection in reducing the intensity of pain was a significant find­ Nonodontogenic toothache of deafferentation origin ing that prompted consideration of nonodontogenic {atypical odontalgia) dental pain.133 Etiology. Deafferentation is a loss of normal afferent The following characteristics of deafferentation input to the central nervous system. Deafferentation toothache can be used to differentiate it from odon­ can result from physical, chemical, or thermal trauma togen ic pain: diffuse pain; pain that is not always to the nerve. Deafferentation symptoms in the oro­ restricted to a tooth (eg, the area may be edentu­ facial region are commonplace. Only a few of these lous); pain that is almost always continuous; a pain conditions, however, elicit pain. The most frequent quality that is often described as a dull, aching, complaints are anesthesia and paresthesia following throbbing, or burning sensation; pain that may or injury of the mandibular nerve that is incidental to may not be relieved by a diagnostic intraoral local the removal of teeth. However, in some instances, anesthetic block; pain that often lasts more than 4 deafferentation can result in pain. When this type months; and pain that is not altered by intraoral ther­ of pain is felt in the region of a tooth, it is often mal stimuli_?,9,56,121,126,131,134 referred to as atypical odontalgia116·117 or sometimes The following are the key clinical characteristics phantom toothache.118·119 of toothache of deafferentation origin: The origin of deafferentation pain appears to be associated with central plasticity in the trigemi­ • The toothache is a continuous pain but often var­ nal nuclear complex of the brainstem.120 In some ies in intensity. There are no periods of remission. instances, there may be a sympathetic component • The most common locations for pain are the max­ to the pain.121 Although no large-scale clinical tri­ illary molar and premolar areas. als have been conducted, atypical odontalgia has • The pain location may change over time but usu­ been estimated to be 10 times more prevalent than ally remains in the same nerve distribution. trigeminal neuralgia and may include up to 3% of • The patient is usually a middle-aged woman with patients receiving pulpal extirpation procedures.54·122 a history of trauma to the painful region.

The possibility of a psychosocial etiology has • The pain is not changed by local provocation. been supported in some studies123 but not oth­ • The effect of local anesthesia is unpredictable. , , 4- ers.116 121 12 126 • The toothache is nonresponsive to dental therapies.

Clinical characteristics. Patients with deafferentation Management considerations. Like many continuous toothache often report a history of trauma or ineffec­ neuropathic pains, deafferentation toothache can tive dental treatment in the area.127 In a study of 42 be difficult to manage. Most of the success comes patients with atypical odontalgia, 86% of the patient from addressing the central mechanisms that seem population was female, and 78% reported maxil­ to dominate the condition. There is some evidence lary pain; of 119 reported areas of pain, the most that tricyclic antidepressants may be of some ben­ common were the molar (59%), premolar (27%), and efit.126·133-135 It is likely that the beneficial effect of canine (4%) regions.124·126 The pain may change in these drugs is not related to the management of location over time; some studies have reported pain depression but instead to the analgesic effects of shifting in up to 82% of the subjects.121·128 Thermog­ relatively low dosages of the tricyclic antidepres­ raphy has been proposed as a diagnostic test, and, sants. These medications inhibit the reuptake of although the differences in facial thermal asymmetry serotonin and norepinephrine, thus increasing the between control subjects and patients with atypical effectiveness of the descending inhibitory system. odontalgia are statistically significant, they are not Dosages ranging from 10 to 100 mg seem to be large in magnitude (18%).129 adequate for pain relief; however, total pain elimina­ It is not unusual for patients with atypical odon­ tion is rare. talgia to have received multiple endodontic proce­ Another drug that that may be helpful is gabapen­ dures or extractions for their dental pain.124-128-130-133 tin (Neurontin).136 Gabapentin may be slowly titrated

461 www.shayanNemodar.com DifferentialDia gnosis of Toothache:Odonto genic Versus Nonodontogenic Pain

Nonodontogenic toothache of cardiac origin

Etiology It has been known for years that cardiac ischemia can refer pain to the arm, neck, face, and even the teeth.97·150-153 The exact mechanism is unknown but is likely related to convergence of nociceptive input originating from the myocardial ischemia carried by

Fig 19-11 Thin acrylic resin stent placed over the teeth and gingival tissue to the vagus and thoracic nerves as they enter the cen­ hold the topical medication over the site of pain. tral nervous system and ascend to the cortex. This phenomenon, accompanied by central sensitization, creates a pattern of pain referral to the face, neck, and arm. It is important that the clinician understand this until pain is reduced or a maximum dosage of 3,600 pattern of pain referral because immediate diagnosis mg is reached.137 The greatest side effect is drowsi­ and referral to the appropriate health care profes­ ness, and that is why the medication is slowly titrated sional is critical. The difficulty in correctly diagnosing to a therapeutic dose. Pregabalin (Lyrica) is a medica­ an acute myocardial infarction is demonstrated in the tion that is similar to gabapentin and has also been frequency of missed diagnoses found in emergency shown to be useful with neuropathic pain.138-140 Prega­ rooms, which ranges between 2% and 27%.154-156 balin can be slowly titrated up to 300 mg/day or until One-fourth of missed diagnoses were found to result adequate pain relief is achieved. in death or potentially lethal complications for the The topical application of capsaicin to the site patient.154 Patients with atypical cardiac symptoms of the painful tooth may also be of benefit.141 Earlier were more likely to be discharged from emergency data suggested that capsaicin applied to the painful departments than patients with typical symptoms.155 tissue appeared to deplete the C fiber of substance An absence of chest pain and a lack of ST elevation P, thus reducing its ability to further stimulate the in electrocardiograms were found to be the main pre­ second-order neuron,1 42·143 although this does not disposing factors for a missed diagnosis.156 In line with appear to be the mechanism for capsaicin analgesia. this, patients with suspected myocardial infarction More recently, it has been found that capsaicin is a but who never experienced chest pain were found to transient receptor potential vanilloid 1 (TRPV1) ago­ run a three times higher risk of death than patients nist that profoundly desensitizes this pain receptor, presenting with chest pain during emergency room reducing nociceptive transmission.144-146 Capsaicin evaluation. These same individuals who never devel­ ointment should be applied to the painful area 4 oped chest pain had an eight times greater risk of

. times a day for 3 to 4 weeks.142•147·148 If this treatment death than patients whose chest pain resolved before is too painful, the capsaicin ointment can be mixed receiving hospital care.157·158 with a topical anesthetic. Other medications, such as amitriptyline, carba­ Clinical characteristics mazepine, and even ketamine,149 have been sug­ Dentists should be particularly aware of the inci­ gested in topical forms to reduce pain. Although dence of jaw and tooth pain that occurs as a sec­ documentation is lacking, this is a relatively con­ ondary manifestation of cardiac pain.153•159 Although servative approach and may be considered. If pain other clinical evidence of cardiac distress (such as relief is achieved but the topical medication is substernal chest discomfort and left arm and neck washed away quickly, a thin acrylic resin stent can pain) is usually present, sometimes the dental symp­ be fabricated to retain the medication on the painful toms may be the only ones reported by the patient. site (Fig 19-11 ). Patients with only dental complaints will certainly come to the dentist with the anticipation that dental therapy will solve the problem.150 Great care should be exercised in such situations.

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In a recent study,160 craniofacial pain was reported Nonodontogenic toothache of psychogenic in approximately 40% of patients who experienced a cardiac ischemic event and was the sole symptom in origin (somatoform toothache) 6% of patients. The data suggest that 1 in every 15 patients experiencing a myocardial ischemic event Etiology or a myocardial infarct will report pain only in the A complete classification of orofacial pain condi­ area of the jaw. The areas most frequently affected tions consists of two broad categories, or axes.7 Axis were the upper part of the throat (82%), the left man­ I includes pain conditions that have their origins in dible (45%), the right mandible (41 %), and the left the somatic (body) structures. For many clinicians, TMJ and ear region (18%). Nonodontogenic tooth­ this represents most pain disorders because their ache was reported in three patients (4%), affecting training has been directed to appreciating how tis­ mandibular teeth bilaterally in two patients and the sue injury, inflammation, and dysfunction can lead maxillary left teeth in one patient. to painful conditions. When no obvious physical The quality of the pain may help the clinician dif­ evidence of disease is present, the clinician may ferentiate this type of nonodontogenic toothache. often describe the tooth pain as an idiopathic tooth­ Although dull, diffuse pain is common, the patients ache.57 Unfortunately, this term is of no benefit to the will often complain of pressure. This symptom is patient because a pain of unknown origin cannot be common with cardiac pain but very infrequently effectively treated. reported with odontogenic toothache.29 Every clinician must understand that a tooth can As with other nonodontogenic toothaches, a lack be painful in the absence of any dental pathosis. In of adequate dental cause for the pain complaint fact, this chapter is dedicated to these conditions. should always be an alerting sign. Failure to arrest However, up to this point, each nonodontogenic the pain with effective local anesthetic blocking of toothache that has been discussed has had a physi­ the tooth confirms that the primary source of pain is cal condition (Axis I) that explained the nociceptive not the tooth.7•153 process that leads to the referred pain experience in The following are the key clinical characteristics the tooth. In each instance, the management of the of toothache of cardiac origin: pain has been directed toward resolving that physi­ cal condition.

• The pain is a deep, diffuse toothache that may There are instances, however, when pain is a sometimes pulsate. significant complaint in the absence of any tissue

• The toothache has pressure and burning qualities. injury or disease. These conditions fall into Axis 11,

• The toothache has a temporal behavior that which represents the psychologic conditions that increases with physical exertion or exercise. may ether be the origin of or a significant contribut­

• The toothache is associated with chest pain, ante­ ing factor to pain disorders. Acknowledgment of the rior neck pain, throat pain, and/or shoulder pain. existence of both Axis I and Axis II factors is basic

• The patient has a prior history of cardiovascular to the effective understanding and management of disease. orofacial pain conditions.7

• The toothache is decreased with the administra­ Psychosocial, behavioral, cultural, and environ­ tion of nitroglycerin tablets (already prescribed by mental factors can impact pain.7·161·162 These factors the patient's physician). can influence a patient's interpretation and report of pain. For example, one study reporting on cultural Management considerations differences in pain language found that 82% of Man­ A complete health history is essential when this type darin-speaking Chinese reported tooth preparations of nonodontogenic toothache is evaluated. The as producing a sourish sensation, whereas only 8% patient may not share his or her entire medical histo­ of English-speaking Americans used this term.163 In ry because he or she is in the dental office for tooth another example, environmental factors were found pain and not having any typical cardiac symptoms. to influence pain reports. In this study, fema l e sub­ When a cardiac toothache is suspected, an immedi­ jects reported significantly greater anxiety and lower ate referral to the appropriate medical personnel is thresholds for electrical pulpal stimulation when mandatory. tested in a dental operatory than they did when test­ ed in a research laboratory setting.164 These studies

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illustrate the fact that the skilled clinician must inter­ • The patient presents with chronic pain behavior pret the patient's pain report with due consideration (eg, frequent use of the health care system, unusu­ given to psychosocial and cultural factors. Moreover, al dependence on others, reclusive nonfunctional clinicians should appreciate the fact that their own lifestyle, or significant use of medications). psychosocial and cultural backgrounds may influ­ • There is no identifiable source of pain, and the ence how they interpret a patient's pain report. clinical characteristics do not fit any other pain There are a few psychologic (Axis II) conditions condition. that are strongly associated with pain complaints. The term somatoform pain disorder is used to Management considerations describe a cognitive perception of pain that has Somatoform pain disorders are mental disorders and no demonstrable physical basis.165-168 Somatoform are best treated by a qualified psychologist or psy­ pain disorders can certainly pose a significant diag­ chiatrist. If the clinician suspects that the patient has nostic problem for the clinician evaluating orofacial this condition, a referral to the appropriate health pain complaints. The clinician might suspect this care professional is indicated. Irreversible dental condition if the patient's pain is not associated with procedures should be avoided because they are any evidence of local somatic tissue changes. This very likely to lead to an unsatisfactory outcome. assumption may be unjustified, however, considering the many pain disorders that have been described in Nonodontogenic toothache of this chapter that are not associated with any obvious source of local tooth pathosis. The clinician must systemic origin therefore always be mindful of somatoform pain dis­ orders so that an improper diagnosis does not lead Certain systemic conditions can result in tooth pain, to mistreatment. including malignant neoplasia, diabetes, sickle cell anemia, and developmental disorders. For example, Clinical characteristics patients with sickle cell anemia may report dental Although it is not always easy to diagnose a somato­ pain that signals an impending sickling crisis rather form nonodontogenic toothache, there are certain than an indication of a local, dental pathosis.170·171 clinical characteristics that will help the clinician. In In a 12-month study, 68% of 51 patients with sickle general, patients will report their toothache as hav­ cell anemia reported dental pain with no evident ing abnormal, unconventional clinical presentations. dental pathosis, yet in other studies, no differences Patients may report pain from multiple teeth that were observed in patients with the sickle cell trait often changes in location and character. The pain compared to controls.172·173 Yet there is also some may even cross anatomical distributions of peripher­ evidence that sickle cell anemia may lead to pulpal al nerves. The pain is often reported as being pres­ necrosis174 (see chapter 20). ent for a long duration (chronic pain) and having not Several studies have reported on various neo­ been responsive to previous appropriate treatment. plastic diseases associated with nonodontogen­ The toothache has no identifiable etiology.7·57·169 ic dental pain. Although the incidences are rare, The following are the key clinical characteristics these reports describe dental pain as an initial or of toothache of somatoform (psychologic) origin: severe symptom in patients with glioblastoma mul­ tiforme 175; metastases from breast, lungs, or pros­

• The pain is reported in many teeth and/or other tate176-178; osteoblastoma179; carcinoma180-182; sar­ sites. coma181; non-Hodgkin lymphoma183·184; and Burkitt

• The pain jumps from tooth to tooth or to other lymphoma.185 Key findings that prompted consid­ locations. eration of a nonodontogenic origin of the dental

• There is a general departure from normal or physi­ pain included subsequent altered sensation (eg, ologic patterns of pain. paresthesia or anesthesia), positive responses to

• There is a lack of response to reasonable dental pulpal testing when a periradicular radiolucency was treatment. present, failure of dental treatment, the diffuse or

• There is an unusual and unexpected response to spreading nature of pain, unusual-appearing radio­ treatment. graphic lesions (eg, diffuse borders involving mul­

• The toothache is chronic and often unchanging. tiple teeth or a moth-eaten trabecular pattern), and

464 www.shayanNemodar.com Conclusions

lack of etiologic factors.175•176•179•180•183•184 In one series • There is inadequate local dental cause for the of 763 patients with nonspecific jaw pain, 1.2% of the pain. population had pain that was caused by metastases • Effective injection of a local anesthetic for the located in the mandible.177 offending tooth does not reduce or eliminate the Patients with multiple sclerosis may present with pain. nonodontogenic dental pain.186 Initially, this may • The toothache has a stimulating, burning, or non­ be the only symptom related to multiple sclerosis, pulsatile quality. which places a difficult diagnostic burden on the • The toothache is constant, unremitting, and non­ clinician. Later, the emergence of electric shock-like variable. pain, as well as the lack of evidence of dental patho­ • The toothache is persistent or recurrent. ses, contributes to expansion of the differential diag­ • The toothache fails to respond to reasonable den­ nosis and prompts evaluation for multiple sclerosis. tal therapy. Multiple sclerosis is typically diagnosed in young women. Hargreaves189 has recommended that clinicians Pulpal pain correlated with the menstrual cycle who treat pain patients remember the classic tale has been reported by some authors.187 Evidence of the blind men describing the elephant. In this suggests that pulp tissue may contain both estrogen tale, each blind man described the elephant as a and progesterone receptors.188 Additional studies completely different animal, depending on whether are required to determine the prevalence, mecha­ he was touching the trunk, ears, or legs. Similarly, nisms, and differential diagnostic evaluation of this clinicians tend to interpret the symptoms and results form of odontalgia. of the clinical examination based on their own focus In some instances, the systemic condition may or training. Clinicians should consider the "whole actually interact with pulp or periradicular tissue, animal" when assessing patients' reports of dental leading to dental pathoses. When this occurs, there pain. Many painful disorders can result in nonodon­ may be a true odontogenic toothache caused by a togenic dental pain. Accordingly, before focusing on systemic condition. Endodontic treatment should be the planned dental treatment, clinicians should care­ performed on the nonvital tooth, but the systemic fully consider the clinical findings and the differential disorder also has to be appropriately addressed. diagnosis. Management may be referral to the proper health To ensure appropriate diagnosis of patients care provider. reporting dental pain, clinicians should follow these The effects of systemic disorders on tooth pain, guidelines: as well as clinical characteristics and management, are reviewed in more detail in chapter 20. • Be diligent in establishing a differential diagnosis.

• Reproduce the patient's chief complaint.

• Determine the etiology of the dental pain. Is the pain of dental origin?

Conclusions • I Consider all local anesthetic injections as diagnos­ tic. Evaluate the patient's response.

• Monitor the treatment outcome.

Toothaches of nondental origin require accurate • Know other area health care professionals who diagnostic identification of the true source of the diagnose and treat pain (eg, orofacial pain den­ patient's pain. The most important step toward tists, neurologists, psychologists, radiologists, and proper management is for the clinician to be suspi­ otolaryngologists) and consult with them when cious that the pain is not of dental origin. The cardi­ necessary. nal warning symptoms of a nonodontogenic tooth­ ache are as follows: Effective pain control is a hallmark of clinical excellence, and this starts with active consideration

• The patient reports spontaneous toothaches involv­ of the differential diagnosis of odontogenic and ing multiple teeth. nonodontogenic dental pain.

465 www.shayanNemodar.com DifferentialDiagnosis of Toothache: Odontogenic Versus Nonodontogenic Pain

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166. First M, Frances A, Pincus H. DSM-IV-TR Handbook of Differential Diagno­ 179. Ribera MJ. Osteoblastoma in the anterior maxilla mimicking periapical sis. Washington, DC: American Psychiatric Association, 2002. pathosis of odontogenic origin. J Endod 1996;22:142-146. 167. van der Bijl P. Psychogenic pain in dentistry. Compend Cantin Educ Dent 180. Miyaguchi M, Sakai S. Spontaneous pain in patients with maxillary sinus 1995;1 6:46,48,50-43. carcinoma in relation to T-classification and direction of tumour spread. J 168. Dworkin SF, Burgess JA. Orofacial pain of psychogenic origin: Current con­ Laryngol Otol 1992; 106:804-806. cepts and classification. J Am Dent Assoc 1987;115:5 65-571. 181. Saxby PJ, Soutar DS. Intra-oral tumours presenting after dental extraction. 169. Ide M. The differential diagnosis of sensitive teeth. Dent Update Br Dent J 1989;166:337 -338. 1998;25:462-466. 182. Sivapathasundharam B, Sivakumar G. Primary de novo intraosseous carci­ 170. Cox GM. A study of oral pain experience in sickle cell patients. Oral Surg noma of the mandible-Report of a case and review of literature. Indian J Oral Med Oral Pathol 1984;58:39-41. Dent Res 2004; 15: 103-106. 171. May OA Jr. Dental management of sickle cell anemia patients. Gen Dent 183. Savitz JB, Patterson DW, Sorensen S. Non-Hodgkin's lymphoma disguised 1991;39:182-183. as odontogenic pain. J Am Dent Assoc 1992; 123:99-100. 172. O'Rourke C, Mitropoulos C. Orofacial pain in patients with sickle cell dis­ 184. Kant KS. Pain referred to teeth as the sole discomfort in undiagnosed ease. Br Dent J 1990; 169: 130-132. mediastinal lymphoma: Report of case. J Am Dent Assoc 1989; 118: 173. O'Rourke CA, Hawley GM. Sickle cell disorder and orofacial pain in Jamai­ 587-588. can patients. Br Dent J 1998;185:90-92. 185. Alaluusua S, Donner U, Rapola J. Nonendemic Burkitt's lymphoma with jaw 174. Demirbas Kaya A, Aktener BO, Unsal C. Pulpal necrosis with sickle cell involvement: Case report. Pediatr Dent 1987;9: 158-162. anaemia. Int Endod J 2004;37:602-606. 186. Currier RD, Martin EA, Woosley PC. Prior events in multiple sclerosis. Neu­ 175. Cohen S, Baumgartner JC, Carpenter WM, Parisi JE, Knuut AL. Oral prodro­ rology 1974;24:748-754. mal signs of a central nervous system malignant neoplasm-Glioblastoma 187. Seltzer S, Toglia J. Nondental conditions that cause head and neck pain. In: multiforme: Report of case. J Am Dent Assoc 1986;1 12:643-645. Seltzer S (ed). Pain Control in Dentistry: Diagnosis and Management. Phila­ 176. Glaser C, Lang S, Pruckmayer M, et al. Clinical manifestations and diag­ delphia: Lippincott, 1978:78-104. nostic approach to metastatic cancer of the mandible. Int J Oral Maxillofac 188. Whitaker SB, Singh BB, Weller RN, Bath KR, Loushine RJ. Sex hormone Surg 1997;26:365-368. receptor status of the dental pulp and lesions of pulpal origin. Oral Surg 177. Pruckmayer M, Glaser C, Marosi C, Leitha T. Mandibular pain as the lead­ Oral Med Oral Pathol Oral Radial Endod 1999;87:233-237. ing clinical symptom for metastatic disease: Nine cases and review of the 189. Hargreaves KM. The elephant. J Orofac Pain 1999;13:77. literature. Ann Oneal 1998;9:559-564. 178. Selden HS, Manhoff DT, Hatges NA, Michel RC. Metastatic carcino­ ma to the mandible that mimicked pulpal/periodontal disease. J Endod 1998;24:267-270.

469 www.shayanNemodar.com www.shayanNemodar.com Interrelationship of Pulp and Systemic Disease

Michaeli A. Huber, DDS

It is conceivable that for any given systemic disease, and 19). Because most of the topics presented in the dental pulp may become involved. This involve­ this chapter represent extensive subjects of study in ment is often a two-way street, as evidenced by the and of themselves, only a succinct overview is pos­ example of diabetes mellitus. It is well established sible. The reader is encouraged to seek additional that poorly controlled diabetes mellitus increases the detailed information as necessary.1-5 patient's risk of suffering an oral infection, including pulpitis. Conversely, poorly controlled oral infection can adversely impact diabetes control. Unfortunately, few studies have purposely assessed the relationship I infectious Diseases between systemic disease and the dental pulp, leav­ ing much of the profession's current understanding to be derived from empiricism and sporadic case Human immunodeficiency virus reports. The clinician must always consider two questions AIDS represents the predominant clinical manifesta­ when managing a patient who presents for care. tion of advanced infection with the human immu­ First, does a systemic condition underlie or contrib­ nodeficiency virus (HIV).6 As of December 2009, the ute to the patient's chief complaint? Second, does World Health Organization estimated that 31.4 to the health status of the patient affect the delivery 35.3 million individuals (14.8 to 17.2 million women, of dental care? To illustrate the first question, con­ 14.4 to 15.4 million men, and 1.6 to 3.4 million chil­ sider the decision points the clinician must address dren younger than 15 years of age) worldwide were to appropriately manage the patient suffering from infected with HIV; of these, 2.3 to 2.8 million became acute sinusitis who presents with odontalgia. To newly infected in 2009.7 illustrate the second question, consider the delibera­ The available scientific evidence clearly reveals tive processing required in determining whether or a dynamic process in which the initial and ongoing not to perform apical surgery on a tooth previously immunologic response to HIV infection is not only exposed to therapeutic irradiation to treat head and unsuccessful in clearing HIV but paradoxically paral­ neck cancer. In both cases, the clinician must inter­ leled by a progressive reduction in immunocompe­ pret the local dental findings in the context of the tence.8 While a cure remains elusive, the introduc­ patient's overall health to develop an effective treat­ tion of antiretroviral therapy (ART) has essentially ment plan. turned this once almost universally fatal infection into The purpose of this chapter is to briefly review a manageable chronic illness. For most HIV-infected selected conditions that may, directly or indirectly, patients, ART effectively stabilizes and normalizes the affect the dental pulp and the delivery of treatment immune system. for various pulpal diseases (see also chapters 2, 17,

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