Traumatic Dysesthesia of the Trigeminal Nerve

Home , Dysesthesia, Formication, Hyperesthesia

Dermot Canavan. B Dent Sc Traumatic injury to the peripheral nerves often results in persistent Postdoctoral Resident discomfort. Substance P has been tmpUcated as a mediator of pain Department of Orofaciai Pain School of Dentislry and depletion of this neurotransmitter has been shown to reduce University of California. Los Angeles pam. Subjects suffering from traumatic dysesthesia of the trigemt- Los Angeles, California nal nerve were treated with capsaicm, a substance P depleter with significant long-term effects. This form of therapy may he used Steven B. Graff-Radford. DDS mdiridtuilly or in combination with other pharmacologie mtervefi- Assistant Research Dentist ttons in the treatment of traumatic trigeminal dysesthesia. Department of Orofacial Pain J OROFACIAL PAIN 1994;S:391-396. University of California. Los Angeles School of Dentistry and Director The Pain Center Cedars Sinai Medical Center Los Angeles, California Barton M. Gratt. DDS Professor Section of Oral Radiology School of Dentistry University of Califomia. Los Angeles raumatic injury of peripheral nerves in humans may resuit in Los Angeles, California pain, dysesthesias, paresthesias, and skeletomotor and autonomie disturbances.' These complaints are often self- Correspondence to: T limiting, but in a certain population, pain or discomfort may per- Dr Steven Grai^-Radford sist. This pain poses a significant clinical management problem. Department of Orofaciai Pain Dysesthesia is usually defined as an unpleasant abnormal sensation, School of Dentistry either elicited or spontaneous.' Paresthesia, in contrast, has been University of California. Los Angeles defined as any abnormal sensation, such as burning, prickling, or CHS 43-009 formication, that is not unpleasant.- Both of these conditions are Los Angeles, California 90024 commonly associated with in|ury to sensory pathways in either the peripheral or central nervous system. The dysesthesia that accom- panies traumatic injury to peripheral nerves has been attributed to deafferentation and hyperactivity of spinal/central pain transmis- sion neurons.' Minor tissue damage associated with pain, without obvious nerve damage, may also lead to the development of the clinical characteristics of a neuropathy.' Although large afferent fibers may show pathologic changes as a result of trauma, small unmyelinated fibers are invariably affected.' Traumatized afferent neurons may generate activity through four possible mechanisms; (Í) neuroma; (2) neurogenic inflammation; (3) trauma; and (4) sympathetically maintained pain. Abnormal sensations resulting from neural injury are therefore the "conse- quence of disorder of the central control systems that establish the normal routing and amphfication of sensory signals.'"' Neurotransmitters are required for the ongoing activation and processing of nociception. Depending on the site of injury or the mechanism producing the pain, different neurotransmitters have been implicated. Substantial evidence exists implicating the neu- ropeptide substance P as one of the transmitters in nociceptive pathways.' It has been proposed that the release of substance P from nociceptors following tissue injury contributes to the spread of neurogenically mediated hyperalgesia and vasodilatation. Substance P, in combination with compounds released irom dam-

Journal of Orofacial Pain 391 Can a van

aged tissues, can further sensitize or activate noci- referred to The Pain Center, Cedars Sinai Medical ceptor afférents. Endogenous neuropeptides, par- Center, where a comprehensive clinical evaluation ticularly substance P,'*"" have been implicated in was carried out. The oral, stomatognathic (tem- the inflammation and pain of arthritic condi- poromandibular joint), myofascial, and cervical tions,'-" In the rat model, substance-P-induced screening examinations were noncontributory. inflammation has been shown to be suppressed by However, the neurologic screening examination capsaicin, which appears to deplete substance P revealed an area of increased sensitivity to light receptors on target tissues. This effect is considered touch bilaterally in tbe mental nerve region which to be long lasting.''' The principal source of cap- reproduced tbe complaint. The recommended ther- saicin (trans-S-methyl-N-vanillyl-6-nonenamide) is apy was a tricyclic antidepressant in combination capsicum, the common pepper plant," with a topical capsaicin (Zostrix), Desipramine Recent reports suggested that the depolarizing hydrochloride was started at 10 mg at bedtime and effect of capsaicin is selective for C-fiber poly- then gradually increased to 30 mg. It was initially modal nociceptor afférents and involves opening a suggested that the patient should apply the capsaicin cream five times a day in the affected area nonselective cation channel.'" Thus the selective for 7 days, then three times a day for an additional nature of capsaicin's influence on C-fiber activity 3 weeks. A topical anesthetic was offered in com- suggests tbat it may be useful in treating pain con- bination with the capsaicin to enhance compliance. ditions triggered by C-fiber input. The efficacy of At 1-year follow-up, the patient reported no pain capsaicin m the management of postmastectomy and continued with 10 mg of nortriptyline hydro- pain syndrome,'' postherpetic neuralgia,'^ cluster chloride and a single use of capsaicin per day. headaches,''' diabetic neuropathy,^" and phantom limb pain^' has been evaluated. Persistent dysesthesia following neural trauma has been reported as a complication of orthog- Case 2 nathic surgery, implant placement, third-molar removal, endodontic therapy, and routine dental A é2-year-old woman, a homemaker, presented procedures,--"" The present report describes the use with bilateral continuous pain in her chin and jaw. of capsaicin as an adjunctive treatment of postsur- The pain was variable in intensity, and at times she gical sensory disturbance involving the trigeminal had a tingling tightness or burning sensation in her nerve. The use of capsaicin was helpful in treating chin. The discomfort had hecn present for 2 years facial dysesthesia after trauma as in the three case following surgery for mandibular advancement reports presented. and mandibular osteotomy. No aggravating fac- tors were described. Aspirin, ice, and heat had been tried with little benefit. She was referred to Case 1 The Pain Center, Cedars Sinai Medical Center, where a comprehensive chnical evaluation was car- A 70-year-old woman, a retired school teacher, ried out. The oral, stomatognathic (temporo- presented with bilateral mandibular stiffness in the mandibular joint), myofascial, and cervical screen- mental nerve distribution. The stiffness was con- ing examinations were noncontributory. The tinuous and associated with pain of moderate neurologic screening examination of cranial nerves intensity. The pam was aggravated by changes in II to Xil was noted to be within normal limits, temperature and relieved by ibuprofen. The prob- with the exception of a decreased reaction to pin lem starred after the woman sustained a bilateral prick by approximately 20% in the V3 (mandibu- fractured mandible in the mental nerve region dur- lar) distribution of the trigeminal nerve. This ing a motor vehicle accident. Initially, a plastic sur- decreased reaction to pin prick was restricted to geon reduced the fracture. She was then referred to the mental nerve distribution bilaterally. An area a dentist who believed that a bone graft was neces- of increased reactivity to light touch was noted in sary before the placement of dentai implants. This the left mental nerve distribution and along the was done by an oral surgeon who placed a stabiliz- right border of tbe lower lip. The treatment recom- ing plate on the left side of the mandible. Later, mended was capsaicin (Zostrix) applied topically three dental implants were placed to support a on the affected site, five times a day for 1 week, complete mandihular denture. The patient's jaw and three times a day thereafter. In addition, the stiffness and pain had continued throughout this patient was placed on a low dose of desipramine time. Because of the pain, the patient was unable hydrochloride to enhance pain relief. At 6-month to masticate properly on the right side. She was follow-up, the patient had no pain and continued

392 Volume 8, Number 4, 1994 Cansvan

to use 10 mg of desipramine hydroch!oride and region. The pretreatment AT values (area tempera- capsaicin daily. ture differences from side ro side) ranged from +0.7''C to +l.rG. Posttreatment thermograms, which were also obtained from all three patients, Case 3 demonstrated decreased heat emission foiiowing cessation ofthe pain. In the affected regions ofthe A retired man, aged 67 years, presented with a face, AT values ranged from .*- 0.2°C to +0.4°C. All bilateral continuous dull aching pain in the preau- three patients had been instructed not ro use cap- ricular region. This pain e?itended to the inferior saicin for 24 hours prior to their thermography half of each ear. The patient also complained of examinations. Figure 1 is an example of a pretreat- continuous tenderness behind the upper half of the menr lateral facial thermogram demonstrating a right ear. The condition had a sudden onset fol- "hot" area (3 cm x 3 cm, yellow area with red ring) lowing face-lift surgery 18 months previously. A over the left cheek of the face. This area was mea- postoperative infection in the left preauricular area sured and found to have increased vascular heat had complicated the surgery. No treatment had emission, judged as being "hot." Figure 2 is an been provided for his continuing discomfort. example of a postrreatment lateral facial thermo- Shaving in the affected areas elicited a burning, gram demonstrating a "warm" area (1 cm x 0.7 cm, sringing sensation. Mastication or touching the yellow spot with red ring) over the same left cheek side of his face also exacerbated his discomfort. area of the face. This area was measured and The patient's sleep was disturbed because of the found to have less increased vascular hear emission resultant discomfort from the pillow touching his and was judged as being "warm." The thermo- face (hyperesthesia); nothing reportedly alleviated graphie examinations were comfortable for the the pain. At the UCLA Pain Management Genter, patient and easy to perform, and all three School of Dentistry, clinical findings revealed nor- patients en¡oyed viewing their own thermal mal inrraoral, stomatognarhic (temporomandibu- images. iar joint), myofascial, and cervical screening. Although an active trigger point was detected in the left masseter muscle, on palparion it failed to Discussion reproduce the patienr's chief complaint. The cranial nerve screening examination identified a hilar- This presentation described three cases of traumat- eral preauricular zone that was hypersensitive ro ic neuralgia rhar responded to combinations of horh light touch and pin prick. The trearment rec- antidepressants and topical capsaicin. Although ommended was to use capsaicin (Zosrrix) cream in there was no control and a combined therapy was the affected areas five times a day for 1 week and used, this combination is believed ro be more effec- then three times a day thereafter. Desipramine tive for neuropathic orofacial pain than rhe use of hydrochloride was prescribed to enhance both either of these agents independently. Although pain relief and sleep. many other therapies that may have been useful At 1-week follow-up, the burning qualiry had for rhis patient population exist, it is suggested disappeared completely, and the parient's sleep that the first line of treatment include a tricyclic had improved significantly. The maximum dose of antidepressant in combination with topical cap- desipramine hydrochloride was 30 mg. At 3- saicin. If this treatment fails, it may be useful ro consider membrane-stabilizing medicarions such as month follow-up, the patient no longer used the carbamazepine, haclofen, phenyroin, mexiletine, or capsaicin because he had developed skin irritation even cionazepam. If the pain is localized intraoral- in the region of application. In addition, the ly, topical anesthetics may be delivered via a neu- patient no longer used desipramine hydrochloride. rosensory shield (stenr) in combination with oral As part of an ongoing facial thermography study medications.'' Consideration must be given during at the UCLA Medical Center, all three patients the work-up to sympathetically maintained pain. received investigational facial thermograms using Should the pain be eliminated by sympathetic an Agema 870 Thermovision unit (Secaus, NY) hlock (stellate block), repeated blockade combined at 0.5°C and 1.0°C imaging sensitivity (0.1"C with anridepressants or membrane-stabilizing med- accuracy). All three patients displayed asymmetric ications may be useful. lateral facial thermograms. Initially, the facial temperature (due ro vascular heat emission) in the Often the question arises whether the antidepres- region of pain was increased, being asymmetric sants are effective secondary to their antidepressant from side to side and rated as "hot" in the affected properties, their effect on sleep, or rhrough anal-

Journal of Orolacial Pain 393 Cana van

Fig 1 Pretreatment thermogram of subject 1. Note Fig 2 Posttreatment thermogram of subject 1. Note elevated temperature ¡yellow area with ted ring) in mid- reduction of "hor" area (yellovJ area with red ring) iti face area. mid-face area.

gesic properties. It is generally accepted that the metabolism of the drug is variable and high doses effect is independent of antidepressant effects; as may render a subtherapeutic level. lower doses are required, rhe titne to onser is more Tbe initial application of capsaicin to skin rapid, and the majority of the pain patients are not causes C-fiber activation and pain; bowever, depressed. Sleep is usually considered to be dis- repeated application causes desensitization and turbed secotidary to the pain, and in itself, may hypalgesia. Despite the large amount of experi- result in lowered pain threshold. There is no con- mental work done with capsaicin, the exact mech- clusive evidence tbat one antidepressant is superior anism of pain remains uncertain. Most studies to another. Therefore, clinical experience must be have used capsaicin that was systematically used to weigh the therapeutic benefits versus the applied to nerve trunks or directly injected into tis- patient's tolerance of side effects. A cautious review sues. In the few studies that have used topically of the patient's previous and current medical his- applied capsaicin, the concentrations were many tory is required to identify conditions, such as times higher than those used clinically." Several arrhythmia and epilepsy, that contraindícate the important issues associated with the use of cap- use of tricyclics. Accommodation to some of the saicin need to be clarified. Substance P is not selec- more bothersome side effects, such as dry mouth or tively depleted by capsaicin. Marked reductions in sedation, can occur if the medication is prescribed the levels of a number of otber peptides (including initially in small incremental doses. Other side calcitomn gene-related peptide, somatostatin and effects (eg, weight gain) may be unacceptable to tbe vasoactive intestinal peptide) bave also been patient and require consideration of an alternative found.'" Rat studies have identified toxic and medication. Intolerance to side effects sbould not degenerative changes in neurons following expo- be confused with lack of efficacy of the medication, sure to capsaicin.-'-" If capsaicin does reduce sub- and under these conditions, a similar medication stance P levels by causing C-fiber degeneration, the within the same group may be tried. When efficacy long-term effect of this, in humans, needs to be is truly in doubt, a medication from a different evaluated. Capsaicin application on neurons has class of anti de pressants should be prescribed. It is diffuse effects, and its pain-relieving effects are suggested that the first choice should be drugs that unlikely to be solely because of reduction of sub- have low anticholinergic properties, such as stance P levels. Until the exact mechanism of cap- desipramine hydrochloride or nortriptyline hy- saicin is understood, chnicians sbould give careful drochloride. Blood levels of these medications are consideration to its long-term use. However, the also sometimes helpful in patients who are not significant pain reduction resulting from the topi- responding to treatment. It has been observed that cal application of capsaicin, in certain types of

394 Volumes, Number4. 1994 Carta van neurogenically mediated pain conditions, warrants 14. Lam FY, Ferrell WR, Capsaicin suppresses substance P- the continued clinical study of capsaicin as an mduced joint inflammation in the rat. Neurosci Lett 1989; analgesic/pain-modulating substance. 105:155-158. 15. Virus RM, Cebhart GF, Pharmacologie actions of capsaicin: Apparent involvement of substance P and sero- tonin. Life Sei 1979;25:]273-1284, References 16. Lynn B, Capsaicin: Actions on nociceprive C-fihres and therapeutic potential. Pain 1990;41:6¡-69, 1. Casey KL, Toward a raciónale for the treatment of painful 17. Dini D, Bertellj G, Gozïa A, Forno CG. Treatment of the neuropathies. In: Dubner R, Gebhart GF, Bond MR (eds). postmastectomy pain syndrome with topical capsaicin. Proceedings of the Vth World Cungrtss on Pain, Pain 1993;54:223-226. Amscerdarn; Elsevier Science l'ublishers BV, 1988; 1 8, Bernstein JE, Korman NJ, Bickers DR, Dahl MV, Miliikan 16S-174. LE, Topical capsaicin treatment of chronic postherpetic 2. Dorland's Pocket Medical Dictionary, Philadelphia. neuralgia, J Am Acad Dermatol 1989^17:265-270 Saunders, 19, Sicuteri F, Ftisco B, Marabini S, Fanduilacci M, Capsaicin 3. Fields HL, Painful dysfunction of the nervous sysceni. In; as a potential medication for duster headache, Med Sei Fields HL (ed). Pain, New York: McGraw-Hill, Res 1988;16;1079-1080, 1987:134-137. 20, Ross DR, Varipapa RJ, Treatment of painful diabetic neu- 4. Janig W, Pathophysiology of nerve following mechanical ropathy with topical capsaicin. N EngI J Med 1989;321: injury. In: Dubner R, Gebhart GF, Bond MR (eds). Pro- 474-^75, ceedings of the Vih World Congress on Pain, Amsterdam: 21, Raynor HC, Atkins RL, Westerman RA. Relief of local Eheviei Science Publishers BV, 1988:89-108, stump pain by eapsaicin cream. Lancet 1989;2:1276-1277, 5. Dyck PJ, Lambert EH, O'Brien PC, Pain in peripheral neu- 22, Campbell RL, Parks KW, Dodds RN, Chronic facial pain ropathy related to rate and kind of fiber degeneration. associated with endodontic therapy. Oral Surg Oral Med Neurology 1976;26:466^71. Oral Pachol 1990;69:287-290, 6. Wall PD. Mechanism of acute and chronic pain. In: Kruger 23, Gregg JM, Srudies of traumatic neuralgias in the maxillo- L, Liebeskind JC ¡eds). Advances in Pain Research and facial region: Surgical pathology and neural mechanisms, J Therapy, vol 6. New York: Raven Press, 1984:95-104, Oral Maxillofac Surg 199Ü;48:228-237, 7. Wall PD. Pain and no pain. In: Coen CW (ed,). Functions 24, Meyer RA, Discussion on Gregg JM, Studies of traumaric of the Brain, O:iiford: Clarendon Press, 1985:44-66, neuralgias in the maxillofacial region: Symptom com- 8. Otsuka .VI, Konishi S, Yanagisawa M, Tsunoo A, Takagi plexes and response to microsurgery. J Oral Maxillofac H, Role of substance P as a sensory transmitter in spinal Surg 1990;4S:141, cord and sympathetic ganglia. Ciba Found Symp 1982; 25, Bashi N, Preventing and resolving complicarions with 91:13-34. OS seo integra ted implants. Dent Clin North Am 1989; 9. Lorz M, Carson DA, Vaughan JH. Substance P activation 33(41:821-868. of rheumatoid synoviocyies: Neural pathway in pachogen- 26, Graff-Radford SB, Differential diagnosis of orofaciai pain. esis of arthritis. Science 1987;235:893-89¿, In: Hardin JF (ed), Clark's Clinical Dentistry, Philadelphia: 10, Levine JD, Clark R, Devor M, et al. Intraneuronal sub- Lippincott JB, 1993il-15, stance P contributes to the severity of experimental arthri- 27, Hölzer, P, Local effector functions of capsaicin sensitive tis. Science 19 84;226:547-549, sensory nerve endings: involvement of tachykinins, calci- 11, Badalamente MA, Cherney SB, Periosteal and vascular tonin gene-related peptide and other neuropeptides, innervation of the human patella m degenerative joint dis- Neurosci ]988;24:739-768, ease, Semin Arthritis Rheum 1989; 18:61-66. 28, Jancso G, Kiraly E, Joo F, Sudi G, Nagy A. Selective 12, Levine JD, Coetzl EJ, Basbaum AL Contribution of the degeneration by capsaicin of a sub population of primary nervous system to the pathopbysiology of rheumatoid sensory neurons on the adult rat. Neurosci Lett 1985;59: arthritis and other poly arthritides. Rheum Dis Clui North 209-214, Aml987;13:369-383, 29, Marsh SJ, Stansfeld CE, Brown DA, Davey R, McCarthy D. 13, Colpaert FC. Evidence that adjuvant arthritis in tbe rat is The mechanism of artion of capsaicin on sensory C-type associated with chronic pain. Pain 1987;28:I277-1289, neurons and their axons in vitro, Neurosci 1987;23:275-289,

Journal of Orofaciai Pain 395 Canavan

Resumen Zusammenfassung

Disestesia traumática del nervio trigérnino Traumatische Dysästhesie des N. trigeminus

Las lesiones traumáticas de ios nervios periféricos a menudo Traumatische Verletzungen der peripheren Nerven resultieren traen como consecuencia una moleslia persistente. Se ha impl¡. oft Ir bleibenden Beschwerden. Substanz P ist als cado que la substancia P es un mediador del dolor, y cuando Schmerzvermitder darnit in Zusammenhang gebracht worden. este neurotrarsmisor disminuye, se produce una reducción del Die Erschöpfung dieses Neurotransmitters hat eine dolor En este estudio, personas que sufrían de disestesia Schmerzreduktion zur Folge. Personen, weiche an einer trauma, traumática del nervio trigémino fueron tratadas con capsaiclna. tischen Dysästhesie des N. trigeminus leiden, wurden mit la cual reduce la presencia de la substancia P, con efectos a Capsaicin behandeit, welches über längere Zeit zur Erschöpfurg largo plazo. Este tipo de terapia puede ser utilizada individual, der Substanz P führt. Diese Form der Therapie kann individuell mente o en combinación con otras intervenciones farmacológi- oder in Kombination mit anderen pharmai^ologischen cas en el tratamiento de ia disestesia traumática dei nervio Interventionen bei der Behandlung von traumatischer trigémino. Dysästhesie des N. trigeminus verwendet werden.

396 Volume 8, Number 4, 1994