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Minimally Invasive Spine Surgery: Current Aspects 229 Red c w 1). (Table

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Most low f 14 26 Simin Hepguler MD 39 Back europathi N When occurs, most common un- ponent o ponent derlying reasons should be taken into consider- ation and one should pay attention to “red flags” which imply very serious conditions. Definition Low back pain is felt in a region ranging can pain the from in- to waistline; cage of rib margin ferior be localized in lumbar region, but it may also radi- ate to the leg. Following a pain-free period of six weeks, sudden-onset pain lasting <6 weeks is re- will term the while pain, back low as acute ferred if it or chronic 6 to if 12 it weeks lasts be subacute lasts longer than 12 weeks. attacks disappear within one week and 90% of pa- tients return to work within 2 months. However, the longer pain lasts, the rate of return to work de- creases, and 50% of patients, who been have suffer- while to work, may return for ing 6 pain months, the chance is very low if the patient has been suf- fering the pain for 2 years. month study period, it was estimated that direct re- month study period, it was CLBP with patients for $ million 96 was cost source for accounted CLBP of component neuropathic and for higher 160% is care of Cost cost. total the of 96% patient than NP with associated CLBP with patients NP with CLBP NP. with associated not CLBP with popula- component is found in 4% of German adult 67% is pain back low neuropathic of cost Care tion. higher than care cost of nociceptive pain. Of the to- for 16% is of cost tal pain, reserved care low back neuropathic component. m Co 26 In a U.S. Study, Study, a U.S. In 29 14 found the NP component in 90.4% 90.4% in component NP the found 29 et al.

Although underlying cause is not cause known underlying Although ow back pain is a frequent problem of mus- is prevalence Life-long system. culo-skeletal in (12-30%) 15% is incidence the and 60-85% 26

Pathophysiology of low back pain is complex

This is the most common and most expensive 36 Mehra M of 39.425 patients with CLBP. the At end of the 12- cent in patients with chronic low back pain (CLBP), (CLBP), pain back low chronic with patients in cent depending on the study method. and the mechanisms leading to both nociceptive and and nociceptive both to leading mechanisms the and (NP) are involved. Rate of neuro- pathic component ranges between 17 and 54 per- reason of occupation-related disability in subjects cost direct The estimated <45 years. who are aged cost total the £ and billion 1.6 was condition the of was 6.6-12.3 billion £ in U.K. in 1998. Moreover, di- con- rect cost is 12.2-90.6 billion $ in USA study was pain back low subjects 30.074 with leads ducted condition the that found study the and 1998 in to 140 million lost workdays per year and the fig- ure is 101, 8 million lost workdays for occupation- related low back pain.

in most cases, compression fracture was found in and - 4% of all low back pain cases, while spondylolisthe spondylitis ankylosing metastasis, or tumor sis, and 0.3% in 0.07%, 3%, determined were infection 0.01%, respectively. It was also found that remain- spraining to mechanical secondary were ing cases of structures forming the lumbar region. L Introduction adults. 230 Minimally Invasive Spine Surgery: Current Aspects ponent. Characteristics of NP are as follows; as are NP of Characteristics ponent. com- pain neuropathic the of occurrence with result lesionA diseaseor somatosensorialof system will ogyof nervous system results with persistent pain. Pathol mechanismofpainiseliminated. underlying - ropathic component. persists althoughropathic component.Onlydiscdisordershave neu- tissue damagepotential.Ingeneral,thereisnoneu- is caused by tissue damage or a signal indicative of low back pain are as follows; as are pain back low anism is involved in spinal axis. Reasons of chronic particularly painindicate thatmore thanonemech- syndrome. Sensorial disorders, motor weaknesspain and and therefore, they are regarded as mixed ponentspain are found in combination Nociceptive understood. fully com- andneuropathic in chronic low back sideration by physicians. by sideration con- into taken be should which conditions, fective include behavior,belief,occupationalhistoryandaf- Those conditionsarereferredasyellow flags and they prolong sick period and may adverselyit since affectconsideration, prognosis.into taken be should malignancy. and tions or very important conditionsinterven - suchemergency as infectionrequiring conditions involve testsandfinalmaketheanddiagnosis, sincethey flags require physicians order further examinations Simin HepgulerMD 4. 3. 2. 1. Acute low back pain is usually nociceptive and it 3. 2. 1. Neuropathiccomponent chronicofnot painis In addition, psychosocial state of the patient patient the of state psychosocial addition, In ceptive pain, and pain mechanisms. pain and pain, ceptive noci- as referred is which pain, of type other Presence of neuropathic pain does not rule grades) (variousout dysfunction autonomic and Otherneurological findings including motor grades various at ) poaesthesia, Presence ofsensorialneurologicalfindings(hy- process recovery normal following Pain and abnormal sensorial symptoms persist Inflammatory effect resulting from chemokin pain) neuropathic (local disc Lesionofnociceptive sprouts indegenerated pain) root neuropathic ical Mechanical nerve compression(mechan- root root pain). root neuropathic (inflammatory disc generated de- from released are which cytokines and 20 16 14

(Table 2) 6 TRPV-1is activated by noxious hot stimulant; after sient receptorpotentialvanilloid 1(TRPV-1)] increases. [including proteins receptor several of tration make contributions.Followingnerve injury,concen- opment of ectopic activity.devel- the Potassiumto contribution channelsmake they alsoand location channelsand α-adrenoreceptors accumulate at this ceptorschemicaland mediators. Excessive ionNa re- of number increases and neuroma in cumulates antegrade axoplasmictransportation;thecontentac- is transported from nerve cell to the periphery with gravationectopicof signal formation. Cellcontent ag- with resulting site, injury at develop Neuromas sitizedandthey become permeable tolow-density sen - are high-threshold consequence, a lipo-oxygenaseof arachidonic acid metabolism. As histamineandP plasmaandcyclo-oxygenase and proteins including serotonin, , Substanceleadvasodilatationto andextravasation plasmaof morestimulation. Activation of ofinflammatorysake the cellsfor nociceptors of sensitivity creases in- cells such by secreted substances Intracellular late at damage site after peripheral nerve is injured. signal. pain of conduction in Underpathological condition, fibersβplay roleA Bothfibers end on laminate I and II of dorsal horn. myelinatedfibersCwith conductionlow velocity. elinated Aδ withhighconductionvelocity andnon- nal cord.Thoseafferentfibersarecomprisedofmy- afferentnociceptivetransmitted by tothespi- fibers changes Peripheral Mechanism PainNeuropathic dition results with heat hyperalgesia. heat with results dition con- Pathological ones. injured in decreases tration creases innon-injurednerve fibers,whiletheconcen - in- TRPV-1 of concentration occurs, lesion nerve pain. neurogenic of persistence and occurrence in ber.believedisIt thattheectopic signals playrole nerveentire fi- the along discharge ectopic causes it lis.Demyelination is secondary to and - spina ofmedulla dorsalhorn on stimulation intense allodynia. and gesia hyperal- primary ”, “peripheral nals; sig- mechanical and thermal to response creased in- with result events those All stimulations. pain α-adrenoreceptors form around dorsal root ganglions Immune cells are activated and they accumu- they and activated are cells Immune are impulses pain conditions, normal Under 42

Final events lead to to lead events Final (Figure 1) 42 5 In addition,In tran- 42

Minimally Invasive Spine Surgery: Current Aspects 231 ). Discharge Discharge ). +2 ) block and Cal- +2 Α-amino-3-hidroxy- 31 ) is secreted into intracellular intracellular into ) is secreted Neuropathic Component of Low Back Pain of Low Back Component Neuropathic +2 ) enters into cell. The results include in- +2 Glutamate exerts effects on AMPA - recep 42 such as , glu- enlargement of area is referred as “wind-up”. This This “wind-up”. as referred is area of enlargement to permeability for sensitizes further event other stimulations. cium (Ca tor and Substance P exerts effects on neurokinin re- ceptor. Calcium (Ca tamate, calcitonin gene-related peptide (CGRP), (CGRP), peptide gene-related calcitonin tamate, γ-aminobutiric acid (GABA) and neurokinin A, are significant substances for dysinhibition and in- ducing central sensitization. 5-methyl-4-isoxasolepropionic acid and(AMPA) N-Methyl-D-aspartate (NMDA) activation is con- stant. space when substance P is binds to neurokinin NMDA of re- channel ion state, steady During ceptor. receptor is blocked by magnesium (Mg creased cellular excitability, oncogen induction and and induction oncogen excitability, cellular creased of NMDA receptor removes (Mg 42 Pain-free mechanical mechanical Pain-free 31 Peripheral modification of high-threshold sensitivity by various factors factors by various sensitivity nociceptor of high-threshold modification Peripheral Figure 1: stimulation activate neurons, which conduct nocice- neurons, stimulation activate and of Hyperexcitability information. ptive sponse to the stimulation is amplified and thresh- old of stimulation decreases. mitted to CNS, resulting with neuroplastic re-or- ganization and changes on dorsal horn of spinal column. Receiver area of CNS enlarges, while re- ary hyperalgesia is dependent on both peripheral and central changes. Excessive sensorial stimula- tion following the peripheral nerve injury is trans- Primary hyperalgesia develops at tissue damage site, site, damage tissue at develops hyperalgesia Primary while “secondary hyperalgesia” develop in intact tissue, which surrounds the damage site. Second- Central Central Changes and sympathetic efferent terminals of the ganglion ganglion the of terminals efferent sympathetic and innerve them. Secretion of noradrenalin from dor- - signal conver sal root ganglions triggers nociceptive sion in (CNS). 232 Minimally Invasive Spine Surgery: Current Aspects fos and c-jun,andfosmake contribution prolongedtheto c- as such products, protein addition, In long-term. inductiontiveareaandoncogens ofshort- inand recep- in changes facilitation, “wind-up’, cause tors recep- NMDA hyperalgesia. secondary and zation sensiti- central disseminate area, receptor enlarges (PG), which conducts stimulant to pholipaseneighbor C results neurons, with synthesis phos- of ofactivation prostoglandinIncreased fields. receptor other inated along presynaptic membrane and sensitizeddissem- is NO expression. gene early and synthase tionofprotein kinase C,phospholipase andCNO tains centralsensitization.Italsoresultswithactiva- in the form of allodynia. It is believed that allodyniatouch.Inneuropathic pain conditions, this sense is inaIIIand IVof dorsal column andthey sense the nervous system. nervous fectof GABA cannot suppress stimulatory ef- effect inhibitory and of glutamate, of effect stimulant its inhib- which GABA and betweenglutamate paired sensitization. Ca (NO). oxide nitric of synthesis Simin HepgulerMD sciaticalgiawilldisappear 24-30 weeks,in while a syndrome. pain myofascial and arachnoiditis and thesis, lumbar facet arthropathy, epidural adhesionlis- spondylosis, stenosis, foraminal and spinal sus, prolap- disc tears, annular are ones common Most NP. back low with resulting reasons many There Pain Back LowNeuropathic of Causes Clinical signal. pain the transmit ,ß byA whichnormallynotdo transmissionofpain stimulation tothe spinal high-velocity cord and system nervenou peripheral in CGRP,asSubstance andadenosinP triphosphate, nociceptorswill cause secration ofmediators, such damage occurs in lumba region. Chronically inflamed injury. nerve after years many even stimulation any without pain to fibers. C by fibers ß A of stimulation and fibers ß A and C between connection presynaptic cord, spinal in formation branch on dependent is occursposterioron horn.This condition maylead damagea occurs innerve root and deafferentation tion, constantly sends pain signals when Under normalconditions, A ßfibersendonlam- In substantialIn partannularof tears, findings of Nociceptors are excited when non-neural tissue 31 In chronic pain, the balance is im- is balance the pain, chronic In 51 51 +2 ion influx main- influx ion 31 In addi- In of nocturnal pain, sleep disorder and antalgic pos- antalgic and disorder sleep pain, nocturnal of otherdysaesthesia; while itdoes nothave patterns dullachepulsation.or Thepain associatedis with stimulationaggravates it,while theinisitform of ture, and it is intermittent; movementstruc- anatomic facilitates or orsprains which mechanicalfactors, dysfunction.Thepain ismechanic, consistent with spondylolysis, listhesis and radiating . radiating and listhesis spondylolysis, iated segment. iated facil- the with muscle of points trigger active the at entrapments causes to the neurogenic inflammationNA that primer lesion of facet, disc or relatedInstitute neuralofHealth declared about the formation of myofascial pain syndrome, a recent study of National nerve. sciatic the presses com- muscle of contraction or spasm and cases all sciaticalgia. and tion irrita- chronic root, nerve spinal around adhesions low spinal surgery and meningitis and they lead to complaints. Epidural adhesion and arachnoiditis fol- ritationandischemia areunderlying causes NPof tion. Inspinalandforaminalstenosis,mechanicalir- intervenemergency requiring condition a - is which nalandsexual dysfunction andsaddle ,intesti- bladder, urinary cause will L2 of pression com- while myelopathy, to lead will cord spinal cantcentraldischerniation, directcompression of signifi- In degeneration. faster with resulting disc, intoneural foramen impairs nutrient supply to the for5-10% of disc herniations accounts prolapsus and herniation Disc NP. of with disc result will root inductionofinflammatory response around spinal mediators from damages disc to epidural space generativeand discdisease. Secretion inflammatoryof de- chronic to leads conditions those of part small ficity is 91 percent. 91 is ficity speci- while 90.9%, is definition this of Sensitivity pain. shock-like electrical and sharp strike, burn, of feeling as defined is pain The ture/movement. therapy. appropriate mining deter- and mechanisms pathophysiological tiating differen- hep variationwill vary.the of Assessment Symptom profile of patients with or without NP will Picture Clinical Nociceptive pain occurs at the site of damage or Although various reasons are claimed for NP in Sciatic nerve lies in pyriformis muscle in 10% of 41 Inaddition, NPmayalso ocucr in 49 15 6 Minimally Invasive Spine Surgery: Current Aspects 233 - 28 The results of the study study the of results The 48 50 Neuropathic Component of Low Back Pain of Low Back Component Neuropathic conducted a study with 464 pa- conducted a study with 47 in order to differentiate neuropathic neuropathic differentiate to order in 8 Sensitivity, specificity and diagnostic OR of this this of OR diagnostic and specificity Sensitivity, The periferic sensitization symptoms and re- more found investigators same study, another In Smart KM et al. They declared that excitative pain is non-me- tients suffering low back pain and/or leg pain with with pain leg and/or pain back low suffering tients found and authors sensitization, central or dominant severity the to proportional not was pain the that structure of damage or . Screening and Clinical Approach a is cases pain back low most of cause assessment Underlying clinical therefore, improve and will factor, who mechanical cases, determining on focus should In the conditions. high-risk but rare, have and late Physicians of College American of 2007 Guidelines recommended is it Society, Pain American the and sults of the same study were: dermatome and cu- taneous distribution of pain, neural injury and pa- thology or mechanic risk history is the movement/ compress of neural tissue and pain/symptom prov- neurodynamic) with its me- ocation (active/passive, chanic/movement tests. (%95 150.9 and 96% 86.3%, as estimated were group CI: 69,4-328,1), respectively. include serious painful painful serious include radiculopathy patients with attack, compression-dependent thermal pain, and mild - sponta allodynia mechanical mild pain, neous hyperalgesia. Mechanical allodynia and - hyperalge that thought was it accordingly, and mild of were sia segment proximal at located was lesion nerve the . Here, damage occurs on affer of horn on end dorsal which branches, central ent spinal cord, and peripheral branches are intact. with combined and unstable and irrational chanic, potent maladaptive physcological factors (i.e., neg- beliefs maladaptive self-efficacy, poor mood, ative and pain behaviors). They also reported that palpa- diffuse/non-anatomic with associated also was tion 91.8%, is group this of Sensitivity tender. and pain while specificity is 97.7 percent. serious pain, poorer health-related life quality, heavier heavier quality, life health-related poorer and pain, depression serious pain, back low with related disability anxiety in patients with NP. component of low back pain. are consistent with the study conducted by Freyn- hagen R et al. - - com- 28 Mahn F et al. The study due to exam- 8 conducted a study, which - en 23 17 et al. In a study of symptom profile and comorbid- Although pains radiating to distal segment of ex- Although pains radiating to distal segment A survey study was conducted with 717 pa- Kaki AM ination with v. Frey hairs and assessment with QST QST with assessment and hairs Frey v. with the ination determining for loss declared group radicular in cold. In the less same study, was sensorial it profile was simi- although group, pseudor-radicular in lar vibration of sense the that found was It significant. group radicular the in 73% of rate at abnormal was it and was group in 47% and pseudo-articular the supports finding This parameter. sensitive most the nerve to secondary pain back low of component NP compression in radicular symptom, although it sug- gests also that subclinical sensorial loss, which is ob ity in painful radiculopathy, served in the pseudo-articular group, supports NP supports group, pseudo-articular the in served component of chronic pain. athy and painful diabetic polyneuropathy. The study study The with painful radiculopathy or post-herpetic neurop- polyneuropathy. diabetic painful and athy found was it and patients 2094 than more enrolled that comorbidities, such as depression, sleep NP. disor- with patients all in same of were anxiety, and der characteristics specific that determined also was It pared sensorial perception differences in patients study enrolled patients with radicular or pain sensorial (pain motor, region, to subpatellar radiating reflex deficit and Laseque test (+)) and with radiation, pain pseu- (nondermatomal pain do-radicular absence of reflex disorder). tients in order to determine neuropathic compo- nent in chronic low back pain, physicians; and and questionnaire patients both by in filled was form radiating from knee to foot, pos- low back pain, pain were reflex patellar negative and sign Laseque itive found in 87, 40, 18.4 and 17.3% of patients, respec- tively, and it was suggested the that In mentioned NP. symp- of findings diagnostic principal are toms one in every found of NP were ≥3 findings study, of three patients. tremity are described as radicular and pseudo-radic and radicular as are described tremity ular pain and such pains are separately assessed, a assessed, separately are pains such and pain ular rolled 1169 patients with chronic low back pain, in pain, back low chronic with patients 1169 rolled authors and pain, neuropathic differentiate to order white tall, found gender, that NP is more common in patients female charac- age, advanced with terized and diabetes hypertension, of history medical race, lum- as medical history of previous smoking as well bar surgery and previous medical treatment. 234 Minimally Invasive Spine Surgery: Current Aspects prognosis in terms of pain and disability. and pain of terms in prognosis takenbe intoconsideration which leadspoor to increase sensitivity, is 29 percent and specificitySensitivity is of contralateral SLRT, whichtivity is done to of SLRT is 91%, while isoftenused.Sensi- (SLRT)orLasequetest raise test specificity is 26 percent. root if pain is severer in leg.diating toParticularly, pain, dural irritation or straightstretched nerve eral testsareofsignificance,whichindicatepainra- leg pain,sev- oflowback physicalexamination On the Examination Physical nal column. back painsecondarytospecificconditionsofspi- low and, stenosis; spinal or radiculopathy with specificlow back pain; low pack pain associatednon- pain: back low of history medical and tion examina- physical of light the in conditions ing follow- of one on focus should physician the that Simin HepgulerMD sideration. red flags characteristicsofpain should bequestioned and • • • • • • • • • • • • • • continence) in- feces urination, in difficulty sciaticalgia, bilateral hesia, spine with proximity close Chronic use of steroids of use Chronic Osteoporosis cancer of history or Suspicion anest- (saddle disorder neurological disabling or Progressive in wound penetrating or infection dermal infection, Urnary fever Idiopathic traumarecent of History 50 than older subjects in trauma Minor years >55 and yearas 20 < Age Lack of response to 6-week conservative therapy conservative 6-week to response of Lack addiction drug IV Immunosuppression Idiopathic weight loss weightIdiopathic pain restig or pain nocturnal Non-relieving T Red flags in low back pain back low in flags Red 1: able (Table 16 13 Inaddition, yellow flags

should1) becarefully takeninto con- When medical history is obtained, all (Table 2) should 16 14 Occupational Social Belief Behavior Affective Recently, VaanRecently, K Boxem complete neurological examination shouldfindings be made.sholddetermined, be otherinor words, a cerebellar findings should be reflexes,assessedvibratory anddisorder, autonomicnon-radiating pain and ofmuscle, sensorial ormotor deficit, decreased/lost 88 percent. 88 ing triad for physical examination of low back pain: back low of examination physical for triad ing 3. 2. 1. and specificity of this triad is not known. not is triad this of specificity and Passive flexion of neck with SLRT. Sensitivity and SLRT, with foot of dorsiflexion Passive standing, is patient while region lumbar Passive flexion of neck and active flexion of of flexion active and neck of flexion Passive Pending suits Pending compensation and requests about Problems environment business Unsupported satisfaction workPoor duty shirking frequently work, of history Poor pain worsen will activity that expectation Th addiction substance or sexual Physical, family/friend retributory Socially family/friend protective Extremely system support of Lack pain back low for expectations Technologicalsolution symptoms somaticMisinterpretation/exaggeration of work to returning fore completelyeliminatedbe be should pain that Believing noxius physically is pain that Believing controlled be cannot pain that Believing Catastrophicthought De-socialization activity life daily in decrease Dramatic rehabilitation to compliance poor or Passivebehavior sleep excess or Impaired skills imitationPoor Irritability symptoms anxietic and Anxiety symptomsdepressive and Depression 20 In addition, posture and gait, weakness T Yellowflags 2: able et al. et 53 recommends follow- recommends 14 - Minimally Invasive Spine Surgery: Current Aspects 235 For NA compo- 40 52 Validity and Validity reli- Oswestry Disabil- demonstrated that that demonstrated 22 18 11,12 et al. 3 Neuropathic Component of Low Back Pain of Low Back Component Neuropathic 4 , MOS-Sleep scale or Daily Sleep 3 50 (Douleur Neuropathique en 4 questions) (Standardized Evaluation of Pain): Radicu- of Pain): StEP (Standardized Evaluation Although SF-MPQ-2 survey, which tests senso- neuropathic tests, forementioned a to addition In DN4 : ID-Pain this test is comprised of 6 questions, Pain DETECT: there is no clinical assessment; nent of low back pain, sensitivity is 80% and spec- ificity is 92 percent. it can be used for differentiating neuropathic com- ponent of low back pain. in diagnosed correctly is pain back low axial and lar while 79%, is sensitivity the and patients all of validated 89% not is it However, percent. 98 is specificity for non-lumbar neuropathic pains. ity Index or Dallas Pain Questionnaire can be used used be can back Questionnaire Pain low Dallas or Index ity suffering patients in disability assessing for advice). A (Class component neuropathic with pain but NP, for scale quality life is no validated There SF-36 or EQ-5D is recommended. while Profile of Mood States or Hospital Anxiety Scale pr Beck depression Scale can be used for as- sessing mood (Class A advice). patient fills in questionnaire form. Sensitivity is 85 Sensitivity form. in questionnaire fills patient percent and specificity is 80 percent. A study con- ducted by Freynhagen R rial and affective characteristics and is derived by for is validated survey, pain the McGill extending component for neuropathic NP, it is not validated of low back pain. Interference scale can be used for assessing sleep, tion), including seven questions about symptom and and symptom is comprised about of 10 questions (1 point for questions each qus- seven including tion), score total a examination; clinical about questions 3 of ≥4 points is deemed as NP. ≥3 a score and patients, by self-reported are which although pain, neuropathic as considered is points no study is conducred to date to assess NA compo- nent of low back pain. ability of Turkish version is tested. version ability of Turkish (NPS) and (VAS) can can (VAS) scale analogue visual and (NPS) scale pain of pain and therapeu- be used for assessing severity determined had studies Since NP. in efficiency severer tical with characterized are NP with disability more patients that quality, life halth-related poorer pain, related with low back pain and presence of depres- sion and anxiety that the scale may differentiate nociceptive pain and and pain nociceptive differentiate may scale the that NP in patients with chronic low back pain.

- 9-10 3 found found 23 painDE- Findings of Findings 7 , ID-Pain and Five questions are about about are questions Five 54 LANSS Assessment (Leeds of Neu- StEP (Standardized Evaluation of Pain). Validity and reliability of the Turkish version of of version Turkish the of reliability and Validity Types of pain induced by stimulation are re- Detailed somatosensorial function assessment instantly; however, they have NP. no suspected diagnostic value clinically with patients of % 10-20 in with patients in used are tests screening Following suspected NA; Neu- Signs), DN4 (Douleur and Symptoms ropathic ropathique en 4 questions), These tests provide help to differentiate patients with with patients differentiate to help provide tests These clinical replace cannot they although NP, potential assessment. They warn the clinician and help start- results produce tests Those therapies. different ing TECT, Screening Tests ferred as allodynic (occurrence of pain with or pain) stim- provoke normally not does which ulation hyperalgesic (occurrence of severe pain with stim- ulation which normally induce pain). toms (hypoaesthesia) is evaluated with sensorial neurological examination. mild pressure is applied which does not induce pain pain induce peated mildly not noxius does stimulation. For which deep pain, applied is pressure mild are results negative and Positive muscle. or joint in - Posi decreased or increased. normal, considered as feeling strike, dysaesthesia, (parasthesia, symptoms tive of burn, electrical shock-like pain) and negative - symp poral summation which occurs with stimulation assessed is it Hz; 0.3 over a at frequency C of fiber whether pain progressively worsens by slowly re- temperature of 20 C° or 40C°). Vibration test is done done is ing cold test and hot Vibration objects on 40C°). skin or C° (metal 20 objects of at temperature with 128 Hz diaposon to determine abnormal - tem should be made in patients with low back pain and and pain back low with patients in made be should touching by assessed be should touch of Sense NP. is test pinprick while skin, on brush or cotton ball a pin; or safety toothpick hairs, Frey Von with done sensation will include touch- assessment of thermal LANSS scale tested. was examination should be compared with that of con- tralateral side. In a study evaluating neuropathic pain in patients in patients pain neuropathic evaluating In a study with chronic low back pain, Kaki Am et al. symptoms, while 2 questions address examination; a examination; address questions 2 while symptoms, 12 points indicatesscore equal NP. to Sen and above sitivity is 85 percent and specificity is 80 percent. 236 Minimally Invasive Spine Surgery: Current Aspects spite all assistive tests. assistive all spite de- assessment, psychosocial and examination ical neurolog- complete history, medical good includes examine only peripheralmyelinated axonal system. ofsensorial fibers. Electrophysiological studies will in order to determine damage at proximal segment matosensorial conduction studies can be performedproximal segmentofdorsalrootganglion.Evokedso- be within normal ranges if the damage is located at bers are involved. Sensorial conduction studies will sion. Pathological result willbereported ifmotor fi- le- root nerve proximal of diagnosis the support to tencyand F-wave latency can be recorded in order considered. be can tomography (CT), if the former one is not available, magnetic resonance imaging (MRI) or computerizedthough conservativeal- response no therapyis there is maintainedand canal forstenotic 6-8or weeks,symptom oneofred flags oriffindings are suggestive ofradicular ings. Only if it is considered thatthe painfind- isclinical secondarywith correlate not do to methods Radiological TestsNeurophysiological RadiologicExamination and Simin HepgulerMD tients on contrary to clinical pa- experiencemany in ameliorated be cannot Pain issue. tory and findings Treatment ofNPinlowbackpain isstillacontradic- Treatment events. independent than rather other each of continuum are involvements that following QSTs, pseudo-articular and radicularexperience of physician. A study had demonstratedcooperation, subjective results anddependence on pensivedevices, theactual significance ofpatient’s ex- of use disadvantagesinclude although jectivity, ob- of terms in useful be may laboratories other of beneficial results and ability to compare withwithphysical resultsexamination. Standardized protocol, nalis or brain. QSTs should be done inspi- medulla combinationin or periphery at mechanism pain of A δ and C fibers. They may determine impairments sorialsubmodalities, sen- including all of large assessment in Aβ and useful small be will tests These Tests(QST) Sensorial Quantitative Distal motor la- motor Distal Examination: Neurophysiological 19 Best diagnostic method 8 all characteristicsaretakenintoconsideration. ical therapy and occupation therapy) therapiesphys- physiotherapy, (cognitive,behavioral, logical after should involve andnon-pharmaco- pharmacological treatment. for made is decision a andthey should betaken into consideration when ety and other mood disorders anxi- shoulddepression, addition, In evaluated. be beshould determined ing sleep disorders and social and emotionalinclud- quality, life states,health-related pain, to addition order to consider a treatment clinicallypain should significant. be reduced at rate In of minimum 30% in cations and the patient should be also informedmedi- of adverseeffects and protocol treatment NP that the patient should be informed about the condition,have a holistic approach. Before treatmentaretaken isinto started,consideration. The treatment should tionalstates ofthepatient andother comorbidities should beprobedindetails.Psychologicalandemo- backpain.underlyinglowThe back lowcauseof of component neuropathic determine to used be neurologicalexaminations are made; scales should tory should be primarily obtained, andwith chronicpain.Therefore, adetailed medical his- systemic and associated commonly are which problems, tional Following examples can be considered; be can examples Following physical examination, w emay plan poly-pharmacy.can make a conclusion based on medicalstood history mechanisms canand shed light on the way.well-under If- the weclarified, be not could NP of nisms mecha- all Although NP. of mechanism main and patients: those for erationwhenpharmacological therapyplannedis ity ofpainmechanismsandpsychologicalemo- heterogene- with related be can fact This studies. of ponent of low back pain are shown in shown are pain back low of ponent pharmacological therapiesusedforneuropathiccom- 2. 1. consid- into taken be should issues Following Thesuccess treatmentof dependentis typeon 5. 4. 3. 2. 1. or the wind-up phenomenon, wind-up the or indicative disorder in centralstimulation sensorial of regulationSummation of pain nociceptors, peripheral der to influence different aspects of NP of aspects different influence to der or- in rational be should poly-pharmacy The avoided are toxicities Organ avoided are disorders Cognitive possible as little as used are drugs Addictive effects adverse Less Hyperalgesia can be indicative of tender in in tender of indicative be can Treatment(Table 3) Table 4. 6 can becan 7 Non- Minimally Invasive Spine Surgery: Current Aspects 237 - - - 1 Neuropathic Component of Low Back Pain of Low Back Component Neuropathic Usually, those drugs should not not should drugs those Usually, 2) (Figure If this approach is followed, patients specified specified patients is If followed, this approach in item 1 can be prescribed topical lidocain patch, patch, lidocain topical in 1 item can be prescribed or anticonvulsant agents, which block sodium channels, and patients specified in item 3 can be prescribed antidepressants and anti-convul- agents. sive be used in combination since many different mech- anisms are involved in NP. 6 can suggest suggest can able 3: Pharmacologic treatment lines of neuropathic pain T -δ ligand, gabapentin or 2 or presence of bilateral findings loss of modulation in afferent pathways, de- of loss with in C crease in association fibers neurons and phe- in dorsal efferent pathways notypical conversion in A β fibers,  - sug may changes temperature and Trofoedema gest a change in sympathetic activation. Allodynia, segmented extension of pain and/ Topical Topical monotherapy or combination of other therapies for patient with localized peripheral NP Secondary TCA amine (nortryptillin, ) or SSNRI venlafaxin) (duloxetine, Calcium channel α Opiod or can be used alone or in combination with first line treatment to induce urgent amelioration of pain for patients with acute acute NA, neuropathic or episodic exacerbation of severe pain or when long time is required for titrating efficient dose of first line tre atment. 3. 4. • • • • Assess patient with respect to non-pharmacologic treatment and start if treatment, required Third step Re-assess pain and health-related life quality often If pain is adequately ameliorated (i.e., mean pain reduction ≤3/10) and there is tolerable side effect, maintain treatment If there is partial reduction (i.e., mean pain reduction ≥4/10), add one of four treatments, which are specified in previous step, following ade If pain does not reduce or adequately reduce although drug is used at target dose for sufficient time (i.e., reduction <30%), switch to one of four four of one to quate trials switch <30%), reduction (i.e., time sufficient for dose target at used is drug although reduce adequately or reduce not does pain If which treatments, are specified in previous step Fourth step If first line therapy fails in the form of monotherapy or combined consider therapy, second and third line treatments or refer patient to an algo logist or multi-disciplinary pain center NP: Neuropathic pain; SSNRI: Selective antidepressant. Tricyclic serotonin re-uptake TCA: inhibitor; First First step Assess pain and make diagnosis of NP; if you are not sure about diagnosis, refer patient to an algologist or neurologist Determine treatment and NA treat underlying to cause due of NP; if you are not sure aggravate about or treatment of underlying with cause, refer patient to relevant physician ameliorate may which gait) instable depression, diseases, hepatic or renal (i.e., comorbidities Determine or which will require dose adjustment or extra treatment Inform patient the diagnosis and treatment plan and determine your actual expectations Second step If possible, treat underlying cause of NP disease Use one or more than one of following medications: 238 Minimally Invasive Spine Surgery: Current Aspects Simin HepgulerMD TENS: Transcutaneous electrical nerve stimulation nerve TENS: Transcutaneous electrical Sacroiliac joint dysfunction joint Sacroiliac pain Myofascial and syndrome Priformis vertebra of fracture Compression syndrome surgery Lumbar failed adhesion, Epidural rigidity arthropathy,Facetsegmented stenosis foraminal and Spinal adhesion epidural Spondylolisthesis, prolapsus,tear,disc Annular Disease T able 4: able Intra-articular injection Intra-articular manipulation Joint exerciseStabilization Acupuncture/TENS injection or Manipulation joint facet Sacroiliac Transforaminalepidural injection Botulinum injection Triggerpoint modalities Thermal programstrengthening and Stretching modalities Thermal Vertebroplasty stimulation cord Spinal adhesions of Lysis Transforaminalepidural operation Spinal Acupuncture/TENS manipulation Joint Transforaminalepidural ablation Radyofrequency injection Facetjoint modalities Thermal exercises Spinal operation Spinal Acupuncture/TENS injection steroidEpidural modalities Thermal exercises Spinal surgery Spine Acupuncture/TENS stimulation cord Spinal Percutaneousnucleoplasty electrothermia Intradiscal Chemonucleolysis injection steroidEpidural modalities Thermal exercises Spinal symptoms radicular of Presence on Treatmentdependent is Treatmentoptions Non-pharmacological treatment option treatment Non-pharmacological If underlying articular dysfunction is suspected is dysfunction articular underlying If facilitation segmented suspected In approach Transforaminal caudal and spasm muscle Relevant suspected is irritation or entrapmentroot Nerve block branch medial Successful injection steroid If synovial cyst exists, percutaneous aspiration or preferenceFlexion spasm muscle Relevant Transforaminal,interlaminar preference Directional spasm muscle Relevant evidence Poor evidence Poor Transforaminal,interlaminar preference Directional Remarks 6 Minimally Invasive Spine Surgery: Current Aspects 239 44 51 Neuropathic Component of Low Back Pain of Low Back Component Neuropathic , and an extension study demon- 46 Nevertheless, there are studies indicating 43 and week 13 There are studies investigating effects of dulox- 45 8.5%). at week to place 60 mg is superior duloxetine that 12 effective effective than placebo at week study of 3 end the to until 11, but maintained be the not ef- could fect scales some in observed is Improvement 13). (week guidelines with is consistent recovery and weekly similar however, used; is mg/day 120 of dose mg. when 60 and mg 20 of doses for valid not duloxetine are with findings higher is effect adverse of Frequency versus (24.1% placebo with mg 120 in comparison strated maintenance of effect at week 41. literature is reviewed, benefits deriving from anti- depressants could not be demonstrated. controlled placebo A pain. back low chronic on etine back low chronic with patients 404 involving study 60 mg is more duloxetine that demonstrated pain When 10-year 10-year When 38 Location of action. This figure is adapted from reference. Studies investigating investigating Studies 3. Table Figure 2: Analgesic effects are different In the light of several meta-analyses meta-analyses several of light the In 30 Antidepressants: Many drugs are used for pharmacological treat- Many drugs are used for pharmacological and systematic review studies, it is recommended to to recommended is it studies, review systematic and if pain back low chronic low in antidepressants use there is no response to other drugs. volves infleunce on noradrenalin, serotonin reuptake reuptake from anti-depressant serotonin effects and the former one in- noradrenalin, on infleunce And volves GABA serotonin, adrenergic, opiod, inhibition, NMDA receptors and inflammatory cytokins and ac- of tivation ion Adverse effects channels. include se- and gain weight vision, blurred mouth, dry dation, urine retension. neuropathic component of low back pain are usu- anti-NP drugs listed in NA ally for short-term used and number drugs of randomized Therefore, con- low. is studies trolled are also used here. ment of NO, while there are strong evidences for 240 Minimally Invasive Spine Surgery: Current Aspects alin group and 5.6% in placebo group. placebo in 5.6% and group alin is9.9%inpregab ofdiscontinuation rate the adition, was similar to that of placebo at the atsecond first phase. phase Inof the treatment, whilebosacral response radiculopathy; period many lum- patientschronic on pregabalin of effects hadinvestigate to response ferred over 600 mg/day, since effects are ispre- doseof300mg/day similar, the sub-doses; equal two but shouldbe 600 mg/day. The dose is administered at startedatdose of150mg/day andmaximum dose and therefore, dose adjustment is easier. The drug is associated with depressive symptoms. Sexual dys- Sexual symptoms. depressive with associated etin20mg,inpatients with chronic lowback pain parox- (SSRI), inhibitor re-uptake serotonin lective placebo controlled study of patients with chronic chronic with patients of study controlled placebo week(s). 1-2 for maintained isreached 6 to 8 weeks later and maximum dose is mg/dayusedthreeisatequal sub-doses. Titration 1800-3600 of dose the finally, tolerability; on ing depend- intervals 7-day to 3- at mg/day 100-300 of 300 mg/day and the dose is increased at increments orders. Gabapentinshouldbestartedatdoseof100- dis- renal with patients in adjusted be should dose edema; peripheral and gain weight vertigo, iness, lin andSubstanceP. Adverse effectsincludedrows- noradrena- glutamate, of secretion decreasing and to α2-δ subnits of N-type voltage-gated Ca channel lowback pain. These drugs exert effect bybinding used to treat the neuropathic component of chronic patients. those in served ob- are disorders sleep and gain weight function, Simin HepgulerMD chroniclumbar radiculopathy resulted withsacral al. et R Baron by conducted was study A effects. adverse less with associated is dose lower weeks. 8 of end the at mg/day, 900-3600 50patients, whowere given gabapentin in atdose of parameters sensorial and Laseque function, tor found significantimprovement inresting pain,mo- Yıldırım radiculopathy, with patients of study 2400mg/day isused, while inplaceboa controlled 900- of dose if improved is quality life and liorated Serpell pain, back low bar spinal stenosis. spinal bar lum- with patients in deficient sensorial and scores medications further improved walkingpeuticexercise, distance,lumbosacral corset painand non-steroid thera- to mg/day 900-2400 of dose at gabapentin of Pregabalin has linear pharmacokinetic properties are pregabalin and Gabapentin Anticonvulsants: Use of Use No positive result could be obtained with a se- a with obtained be could result positive No (50-400 mg) in patients with with patients in mg) (50-400 topiramat 54 . found that pain is ame- is pain that found al. et 30 30 In a double-blinded, double-blinded, a In 51 Addition 8 inorder et al. et -

studywhichdid notexclude radiculopathy group conductedopenlabel,randomized,a multi-center mouth, nausea, constipation, drowsiness,ate in neuropathic numbness, pain. moder- is Adverseeffect the while effectspain, nociceptive includein tive dry effec- is It impulses. pain of pathways amelioration tors and they regulate generation, transmission and inboth nociceptive andneuropathic pain andside zationlists it as second line treatment. It is efficient Organi- Health World noradrenalin. and serotonin tivates μ- receptor, and inhibates re uptake of in one month of therapy. of month one in drug should be switched if there is no opioidsresponsetherefore,and doseshouldchanged bewith or finitive rule thatde- no patientsis There drugs. withof group NP this respondon started are to strong substance addiction and comorbities, when patientscalhistory should be obtained, Medi- including pain. back low drug andof use on conducted studies vomiting. and pruritus effects include nausea, , drowsiness and and drowsiness headache, nausea, include effects placebo. with ison compar- in waspain difference leg no in and found used and only 28 patients could complete the studypatients 55 withradicular pain,oralmorphin was smalloids.agroupIn patients,of whichinvolved opi- scarce studyon can beconductedsincethereis morefrequent morphinin group. meta-analysisA was constipation of complaint the however, pain; ameliorated agents Both months. 13 for hours) 12 ery72hours) orconstant oral morphin (30ev- mg per at (25μg/h, phentanly transdermal either used they and , strong to naive are who pain back low chronic with patients 680 enrolled and (p<0,03). group placebo than quent fre- more were they but therapy, opioid of fects ef- adverse typical to similar are oxymorphone of effects Adverse group. placebo in effect of lack to due therapy discontinued patients more and apy, ther- opioid previous and gender age, of respective cant improvement isobserved inVAS painscore, ir- moderate orsevere chroniclowbackpain,asignifi- ER in retrospective pooled data of 347 patients with and may tolerate the drug. the tolerate may and patients who does not respond to alternative agentsrecommendeddrugis second-lineas treatment in anxiety and rash in ¼ of patients and therefore, thisparesthesia, nausea, sedation, amnesia, depression, Opioids: Thesecompoundsbindtoopioidrecep- is a central effective isacentral Tramadol analgesic,- whichac oximorphone and placebo of comparison On 25 30 There is no high-quality high-quality no is There 24 33 Allan L et al. et L Allan 2

Minimally Invasive Spine Surgery: Current Aspects 241 - com- 32,37 Celecoxib and 30 21 25 Neuropathic Component of Low Back Pain of Low Back Component Neuropathic 36 and tramadol + paracetamol 35 In addition, it was determined that buprenorphin buprenorphin that determined was it addition, In Considering studies of opioid combinations, and cognitive, behavioral, physical treatment and in addition be used should methods rehabilitation to medications. alin monotherapy. Baseline dose was consistent the and condition, the of dose recommended with dose was increased until optimal analgesia toler- ability was obtained. In conclusion, amelioration of pain and constant maintenance of pain and im- provement of life more quality was were therapy stronger in Combined com- group. therapy bined stable and dose of oxycodone was decreased rate by the addition, In patients. of group this in 22% 5.9% was in due effects to adverse of withdrawal and 10.4% was rate same while therapy, combined 19% in oxycodone CR monotherapy and pregaba- lin monotherapy, respectively. Conclusion issue of low is pain back a Treatment challenging with for all physicians dealing with this Patients problem. - Thera pain. back low chornic in fail may pies chronic low back pain should be re-assessed, component, con- of neuropathic possibility the sidering is concurrently decreased. Combination - thera and effects, adverse more with associated are pies the be at drug should started low therefore, dose and the dose is increased until effective and toler- drug-drug is problem Another found. is dose able interactions. Constant dose combinations will re- duce frequency of this problem. were combination used as pregabalin non-opioid for treatment of chronic low-back pain and the re- (pain effectiveness more showed study this of sult single their with as compared effect) and adverse - in combina is lower use. Mean drug consumption mono with pregabalin therapy in comparison tion therapy (p<0,05). 409 refractory patients, who suffer from neuro- pathic pain mostly secondary to radiculopathy, of were given either free pregabalin combination and oxycodone CR (controlled release) or pregab- + gabapentin binations has stronger effect and less adverse effect effect adverse less and effect stronger has binations drugs. these of monotherapies with comparison in morphin in observed be could success no However, + nortryptillin combination. 27 1 34 plasters is exerted by by exerted is plasters lidocain Guidelines recommend combination therapy The agent is approved for moderate and se- Further studies are required for other topical Combination Combination Therapy in fails NP. The recommendation if monotherapy consumption drug while pain, of amelioration aims ways ways in brain and thus, the pain is further inhib- ited. Phase III study was back conducted low with was 8000 model pa- pain chronic of one and tients (comparator studies comparison studies, Dose pain. year) (one is oxycodone), studies of efficiency administration in pure neuro- long-term and pain effects pathic exerts it conclusion, In completed. are studies it while pain, neuropathic and in nociceptive both has fewer adverse effects discontinued in comparison patients with oxy- fewer that found is it codone; the drug due to adverse effects. release of neurotransmitters in efferent pain path- vere vere acute pain in U.S., and authorization is pend- It pain. chronic and acute severe for Europe in ing release inhibits it therefore, and agonist μ-opioid is pain fi- of excitatory neurotransmitters from afferent bers and pain cannot be transmitted to central ner- it regulates effect, on μ-opioid Based system. vous gesic, which inhibits reuptake of noradrenalin, and it it and is a μ-opioid receptor agonist and an anal- Tapendatol noradrenalin, of reuptake inhibits which and gesic, efficiency of terms in molecule well-balanced is safety in comparison with classical opioids. preparations containing capsicum. Other agents fect is observed in 63% of all patients and the effect effect the and patients all of 63% in observed is fect is maintained after plaster is detached. ing chronic low back pain, remarkable clinical ef- Topical Topical Procedures Analgesic effect of 5% fibers pain damaged of trigger systemic no aberrant has decreasing preparation this channels; sodium in effect. In a study conducted with 40 subjects suffer- numbness (somnolence, lethargy). Baseline dose is dose Baseline lethargy). (somnolence, numbness mg 400 to up increased be can it and day per risk mg the 50 although addiction, of risk is There day. per is not as high as for if opioids; ocur it may may reduce thresh- syndrome serotonin and seizure of old it is used in combination with SSRIs. 242 Minimally Invasive Spine Surgery: Current Aspects 12. References Simin HepgulerMD 13. 11. 10. 9. 9. 8. 7. 6. 5. 4. 3. 2. 1. Attal N. Neuropathic pain: Mechanisms, thera- Mechanisms, pain: Neuropathic N. 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