Neuropathy, Neuropathic Pain, and Painful Peripheral ... · Neuropathy, Neuropathic Pain, and...

Neuropathy,NeuropathicPain,andPainfulPeripheralNeuropathy

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IntroductionThisarticleisintendedforpatients,caregivers,andthegeneralpublic,aswellasdoctorsandmedicalspecialists.Ithasthreesections.Thefirstdefinesneuropathy.Thesecondgivesabroadoverviewofneuropathicpain.Thefinalsectionconcernspainfulperipheralneuropathy,acommonneurologicalcomplaint,itscauses,diagnosisandtreatment.I.WhatIsNeuropathy?Neuropathyisaconditionthatresultsfromdamageto,ordysfunctionof,thenervoussystem.Mostoften,thedamageexistsintheperipheralnervoussystem,whichliesbeyondthespineandbrain,althoughbraininjury,suchasstroke,canalsoresultinneuropathicsymptoms.Thesymptomsofneuropathydependontheunderlyingnerveswhosefunctionhasbeenaffected.Neuropathythatdamagessensorynervescancausenumbness,weaknessandstabbingorburningpain–symptomsthatmayworsenifnottreatedearly.Iftherehasalsobeendamagetothetypeofnervesthatconveythesenseoftouch,vibration,andtemperature,patientsmayexperiencetingling,numbness,orthesenseofwearinganinvisiblegloveorsockovertheirhandsorfeet.Ifthereisdamagetomotornervesthatcontrolstabilityandmovement,patientsmayhavealackorcoordination,weakness,orcramping.

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Finally,iftheautonomicnervesthatregulateinternalorganfunctionhavealsobeendamaged,patientsmayexperienceareductioninsaliva,tears,perspiration,orotherorganorglanddysfunction.TheImpactofNeuropathyNeuropathyisaleadingcauseofchronicpain,whichpersistsforthreemonthsormore.About8%ofpeoplewhoreportchronicpainsufferfromsomeformofneuropathy,whichaffectsabout20,000peopleintheU.S.and15millionintheU.S.andEuropecombined,accordingtotheAmericanChronicPainAssociation.II.NeuropathicPainAnestimated10%ofthepopulationhasneuropathicpain.Althoughtheconditionmaybelifelong,neuropathicpaincanoftenbereducedandevencontrolled,whenmanagedbyspecialistswhocombinetreatmentsthatmightincludemedications,injectionsandevennervestimulation(neuromodulation).

Neuropathyisaleadingcauseofchronicpain,includingpainfulperipheralneuropathy

Neuropathy,NeuropathicPain,andPainfulPeripheralNeuropathy—Manykinds,causes,andtreatmentsReviewedbyNickChristelis,MBBCH,FRCA,FFPMRCA,FANZCA,FFPMANZCACo-chair,InternationalNeuromodulationSocietyPublicEducation,Outreach,andWebsiteCommittee,2016-DirectorandCo-FounderVictoriaPainSpecialists,Richmond,Australia

August2017

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Thenerveinjurygeneratingthisdisorderedresponsemaybefromaspecificincident(anaccident,stroke,oramputation),oradiseasesuchasdiabetes,aviralinfection,orneurodegenerativecondition.Theproblemmayoccurinthecentralnervoussystem(spineandbrain)orperipheralnervoussystem(smallernervesoutsidethespinalcolumn).Typicalcasesofneuropathicpainincludenervepainfromspinaldisorders,includingpainthatpersistsaftersurgerythoughtlikelytocorrectit(failedbacksurgerysyndrome[FBSS]);post-amputationpain;chronicpainfromothernervetraumaorinjury;complexregionalpainsyndrome;andneuropathiesthatmayoccurafteraviralinfectionorfrommetabolicdisorderslikediabetes.PatientswhohaveFBSSmayhavebuttockandlegpainaswellasassociatedbackpainthathasabasisthatmaygobeyondneuropathicpain,involvinganotherpainsystemcallednociceptive.Insuchcases,thepainisconsideredofmixedoriginandtreatmentstrategieswilltakethisintoaccount.Likewise,complexregionalpainsyndrome(CRPS)is–asitsnamesuggests–complex,oftenwithcomponentsofnociceptiveaswellasneuropathicpain.(1)Inmanyways,thesensationofneuropathicpainisunique.Theareaofpainmaybewidespread(diffuse),orlimitedtoasinglenerveorseveralnerves.Thepainmaybedescribedvariouslyasfeelinglikeastabbing,burning,electricshock,orafreezingsensation.Itmayworsenatnight.Somepeoplemayexperiencetemporarynumbness,tingling,andprickingsensations,sensitivitytotouch,ormuscleweakness.Othersmayexperiencemoreextremesymptoms,suchasburningpain,musclewastingorevenparalysis.Asachroniccondition,neuropathicpainimpactsfunctionandqualityoflife.Neuropathicpainunderliesanestimated30-65%oftheactivityseenathospitalpainclinics.Inseverecasesofchronicpain,thehealth-relatedqualityoflifeisrankedasworsethanotherpainconditions,heartfailure,orevencancer.(2-3)TypesofPainwithNeuropathicOriginPainthatfallsunderthebroadcategoryofapainofneuropathicoriginincludesneuralgia,suchasthefacialpainsyndrometrigeminalneuralgia.Anotherpainofneuropathicoriginisneuritis.Neuritisiscausedbyinflammationofanerveorgroupofnervesandmaybeaccompaniedbyfeverandswelling.Someoftheprocessesactiveinneuropathicpaininvolve,tosomedegree,changesinpartsofthenervepathwaythatprocesspainsensations.Releaseofthebody’sownpain-reducingchemicalsmaybedampened,andsomenervecellsalongthepathwaymaybecomeexcitableandoverlyactiveinsignalingpainmessages.Therefore,regardlessofwheretheoriginalnerveinjuryoccurred,inmanyinstances,thecentralnervoussystemcanplayaroleinthecontinuedexperienceofchronicpainsymptoms.(4)

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Someofthespecifictypesofdisorderedpainthatmaybeexperiencedinneuropathyinclude:

Allodynia–painfromwhatisnormallyanon-painfultouch,suchasbeingstrokedbyafeather

Dysesthesia–anunpleasantfeeling,whichisnotactuallypainfulperse

Hyperpathiaorhyperalgesia–prolongedorseverepainfromalightlypainfulincident,suchasapinprickParesthesia–unusualsensations,suchaspinsandneedlesoraburningsensationCentralorPeripheralPainWhilesomeneuropathiesoccurbecauseofdamagetoperipheral(small)nervesandnerveendings,othertypesofneuropathicpainhappenafteraninjuryinthecentralnervoussystem(brainand/orspine).Theseneuropathicpainconditionsthatariseinthebrainorspinearecalledcentralpainsyndromes.Oneexampleofacentralpainsyndromeispost-strokeshoulderpain,whichisestimatedtooccurinuptoone-thirdofstrokesurvivors.(5)TreatmentofNeuropathicPainTheunderlyingcauseormedicalproblemshouldalwaysbetreated.Thiscanreduceorstopdamagetothenervoussystem.Oncetheunderlyingcausehasbeentreated,subsequenttreatmentsshouldfocusonreducingtheremainingsymptomsthatmightbeongoing,whichmayincludeneuropathicpain.Tomanagepainthatcannotberelievedbyover-the-countermedications,standardmedicaltreatmentincludesanticonvulsantorantidepressantmedicationsthathelpreducenervepain.Sometimes,paincreams,patchesoreveninjectionsmayrelievesometypesofnervepain.Incaseswheremedicationsareineffectiveorcauseintolerablesideeffects,

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neuromodulationtherapyusingspinalcordstimulation(SCS)orperipheralnervestimulationmaybeconsideredasanoptiontoreducepain.In2008,theUnitedKingdom’sDepartmentofHealthpolicymakingadvisorygroup,theNationalInstituteofClinicalExcellence(NICE),issuedguidancethatSCSshouldbeusedformedicallyresistant(refractory)neuropathicpain,findingitbothclinicallyeffectiveandcost-effective,withlowerlifetimehealthcarecostandbetterlong-termoutcomes.(6-7)Typicalcasesinwhichneurostimulationmaybeusedincludechronicpainfromfailedbacksurgerysyndrome,post-amputationpain,othertraumaticneuropathies,complexregionalpainsyndrome(CRPS)andmetabolicandviralneuropathies.(8-10)In2015,awidersetofSCSoptionsemerged.Newerstimulationpatternsandfrequenciesarenowavailable.Anothernewermethodtargetsastructurealongsidethespinalcord,thoughttoactasarelystationforsendingsensoryinformationtothebrain,thedorsalrootganglion(DRG).TheDRGisabundleofnervecellbodieslocatedattheedgeofeachspinesegment.Aclinicalinvestigationpublishedin2015showedthatstimulatingtheDRGhelpedprovidereliefforsomepainfulareas,suchastheextremities,thathadbeenhardtoreachwithconventionalSCS.(11)

Forsomepatientswithmedication-resistantcentralpain,deafferentationsyndromes,ortrigeminalneuralgia,twotypesofimplantedbrainstimulationsystemshavebeenreportedtoprovidesomerelief:motorcortexstimulationordeepbrainstimulation.(DeepbrainstimulationiscommonlyusedinmovementdisorderssuchasParkinson’sdisease.)(12)Anon-invasivetypeofperipheralnervestimulationthatisdeliveredthroughtheskin,transcutaneouselectricalnervestimulation(TENS),hasalsobeenreportedtoimprovesymptomsofdiabeticperipheralneuropathy.(13)III.PainfulPeripheralNeuropathyPainfulperipheralneuropathyisacommonneurologicaldisordercharacterizedbynumbness,weakness,tinglingandpain,oftenstartinginthehandsorfeet.PrevalenceandIncidenceofPeripheralNeuropathyPeripheralneuropathyisacommonproblem.Morethantwooutofevery100personsareestimatedtohaveperipheralneuropathy;theincidencerisestoeightinevery100peopleforpeopleaged55orolder.(14)TypesandCausesofPeripheralNeuropathyTherearemorethan100differenttypesofperipheralneuropathy,accordingtotheU.S.NationalInstituteofNeurologicalDisordersandStroke(NINDS).Assaidearlier,thesymptomswilldependonthefunctionoftheunderlyingnerveornervesaffected.Peripheralneuropathycaneitherbeinherited,ordevelopduetoinjuryorillness.Forinstance,adiseasemaycausenerveendingstobecome

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sensitizedandsignalpainwithoutanobviouscause.Orthenervecelloutersheath,themyelincoating,coulddegenerateanddisruptnormaltransmissionofnervesignals.Some30%ofperipheralneuropathiesoccurasacomplicationofdiabetes,andanestimated26%ofpatientswithdiabeteshavesomedegreeofdiabeticneuropathy,duetoprolongedeffectsofhighbloodsugarlevels.Inanother30%ofcases,theprecisecauseofapainfulperipheralneuropathyisunclear(or“idiopathic”).Otherneuropathycausesincludephysicalinjurytoanerve,tumors,exposuretotoxins,alcoholism,kidneyfailure,autoimmuneresponses,nutritionaldeficiencies,shingles,HIVinfection,andvascularormetabolicdisorders.(15)PeripheralNeuropathyTerminologyIfonlyonenerveisaffected,theconditioniscalledmononeuropathy.Ifseveralnervesareinvolved,thedisorderiscalledmononeuritismultiplex,andiftheconditionaffectsbothsidesofthebody,itiscalledpolyneuropathy.Theconditionmaybegeneral,orlocatedinaparticulararea,whichiscalledfocalperipheralneuropathy.FocalorMultifocalPeripheralNeuropathiesFocalormultifocalperipheralneuropathiesinclude:

Carpaltunnelsyndrome(causedbypressureonthenerveduetoinflammationfromrepetitivestress),orotherso-called“entrapment”syndromes

Radiculopathies,includingsciatica(ashootingpaininthearmsorlegsduetoirritationorcompressionofthenerverootinthespine)

PhantomlimbpainandstumppainPost-traumaticneuralgiaPostherpeticneuralgia(15)

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GeneralizedPolyneuropathiesGeneralizedpolyneuropathiescanbepresentdueto:

DiabetesmellitusDemyelinatingconditions(Guillain-BarreSyndrome;chronicinflammatory

demyelinatingpolyneuropathy;CharcotMarieToothDisease(TypeIorII)AlcoholismAutoimmunedisease(rheumatoidarthritis,lupus)HIV(causedbythevirusitself,bycertaindrugsusedinthetreatmentof

HIV/AIDSoritscomplications,orasaresultofopportunisticinfections)(16)VitaminBdeficiencyToxinexposure(whichmayincludesomechemotherapydrugsoranti-

retroviralagents;illicitdruguse,suchasglue-sniffing;orexposuretoheavymetalsfoundinindustrialsettingssuchasarsenic,lead,mercury,andthallium)(17)SymptomsofPainfulPeripheralNeuropathySymptomsandprognosisvary.Inpainfulperipheralneuropathy,thepainisgenerallyconstantorrecurring.Thepainfulsensationsmayfeellikeastabbingsensation,pinsandneedles,electricshocks,numbness,orburningortingling.Symptomsindiabeticpolyneuropathyandothergeneralizedneuropathiestypicallystartinthehandsorfeetandclimbtowardsthetrunk.Oftenthepainismosttroublesomeatnightandcandisturbsleep.Thesensationsmaybemoresevereorprolongedthanwouldbeexpectedfromaparticularstimulus.Forexample,someonewhohasfacialpainfromtrigeminalneuralgia(ticdoloreaux)mayfinditexcruciatingtohavesomethingbrushacrossacheek.Evenalightbreezeorwindmaytriggerthepain.Thenatureofthepainmayfeeldifferentthanpaincausedbyanormalinjury.Neuropathymayaffectnotonlynervesthattransmitpainmessages,butalsonon-painsensorynervesthattransmitothertactilesensations,suchasvibrationortemperature.Painfulperipheralneuropathymayalsooccuralongwithdamagetomotornerves,ortoautonomicnervesthatgovernbasicphysiologicalstates,suchasbloodpressure–bothofwhichcausenon-sensorysymptoms,suchasmuscleweaknessorlightheadedness.DiagnosisofPainfulPeripheralNeuropathyDiagnosisofpainfulperipheralneuropathymayrequireseveralsteps.Aclinicalexaminationwillinvolvetakingacompletepatienthistoryandcheckingtendonreflexes,musclestrength,motorfunctionandthesenseoftouch.Additionally,urineandbloodspecimensmayberequestedtocheckformetabolicorautoimmunedisorders.Othertestsmightbeneeded.

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Follow-uptestsinthediagnosisofpainfulperipheralneuropathymayinclude:

Nerveconductionvelocitytestingtoseehowfastelectricalsignalsmove;and

Electromyography,whichmeasurestheelectricalimpulsesofmusclesatrestandduringcontraction

Forfacialpainsyndromes,brainscansusingcomputedtomography(CT)and/ormagneticresonanceimaging(MRI)

Aspinaltap(lumbarpuncture)totestforbreakdownofmyelin

AbiopsyofthenervesmayevenbeorderedtoinspecttheextentofnervedamageTreatmentsforPeripheralNeuropathyOnceneuropathyhasdeveloped,fewtypescanbefullycured,butearlytreatmentcanimproveoutcomes.Somenervefiberscanslowlyregenerateifthenervecellitselfisstillalive.Eliminatingtheunderlyingcausecanpreventfuturenervedamage.Goodnutritionandreasonableexercisecanspeedhealing.Quittingsmokingwillhaltconstrictionofbloodvessels,sothattheycandelivermorenutrientstohelprepairinjuredperipheralnerves.Mildpainmayberelievedbyover-the-counteranalgesic(painrelief)medication.Forpatientswhohavemoresevereneuropathicpain,anticonvulsantsorantidepressantsarecommonlyprescribed;theiractiononthecentralnervoussystemcancalmoveractivenerves.Topicalpatchesthatactthroughtheskin–forinstance,deliveringtheanestheticlidocaineorchili-pepperextractcapsaicin–mayalsoprovidesomerelief.Anotheroptionisadministrationofalocalanestheticandsteroid(cortisone)blocks.

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Whenpaindoesnotrespondtothosemethods,alternativescanincludecannabinoidsoropiateanalgesics.Ifthesemeasuresareineffective,inasmall,selectgroupofpatients,opioidsmaybegraduallyintroducedaftercarefullyconsideringconcernsandsideeffects.(18)Meanwhile,torelievethemostseverecasesofneuropathicpain,nervesmaybesurgicallydestroyed,althoughtheresultsmightbeonlytemporaryandtheprocedurecanleadtocomplications.Forsomepatients,atreatmentregimenwillalsoincludephysicaloroccupationaltherapytorebuildstrengthandcoordination.NeuromodulationMayBeanOptiontoManagePainfulPeripheralNeuropathyIncasesinwhichdrugsareineffectiveorsideeffectsintolerable,anoptionforsomepatientsmaybespinalcordstimulationorperipheralnervestimulation.By2017,about34,000patientsayearwerereceivingspinalcordstimulation(SCS)implants.ThetherapywasfirstFDA-approvedtomanagechronicpainin1989.Spinalcordstimulationstartswithatrialphase.Inasterilesetting,aslimelectricalleadwithaseriesofelectricalcontactsisguidedbeneaththeskinintotheepiduralspaceabovethespinalcord.Thepatientgoeshomewithanexternalbatterypackthatprovidesneurostimulationforseveraldays.Ifthistrialtreatmentreducespainfrom50-70%,thepatientmaychoosetoreceiveapermanentsystem.TopowerapermanentSCSsystem,inafollow-upprocedure,apacemaker-likepulsegeneratorisimplantedbeneaththeskin.(19-20)Patientsmustcarefullyfollowinstructionstopreparefortheprocedureandabidebyafewrestrictionsoncetheimplantisinplace,suchasavoidingbendingortwistingmotions.Likeallsurgicaltreatments,receivinganimplantcarriesrisksofinfectionorbleeding.Hardware-relatedcomplicationsmayalsoarise.Mostcomplicationsareeasilyreversed,butSCSimplantsdoposeasmallriskofmoreseriousproblems,suchasneurologicinjury.Sometimesspinalcordstimulationeffectivenessmaylessenovertime.Inpatientswhoeventuallydevelopatolerancetoneurostimulation,apotentialfutureoptionisdeliveryofapain-reliefagenttotargetedsitesinthebody,usinganintrathecaldrugdeliverysystem.Forinstance,ziconotide,anon-opiatedrugnowoftenemployedtotreatcomplexregionalpainsyndrome(CRPS),hasbeensuggestedbyspecialistsasapossiblyviablealternativepain-reliefagent.(21)Forappropriatelyscreenedpatients,meanwhile,peripheralnervestimulatorscanhavean80%to90%near-termsuccessrate.(22)ConclusionIrrespectiveofthetypeofperipheralneuropathytheyhave,manypatientscanfindsomereliefiftheunderlyingcauseisaddressedandaholistictreatmentapproachismaintained,buttheywillrequirecarefulinterdisciplinarymonitoringandfollow-up.

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Forfurtherinformationsee:WIKISTIMathttp://www.wikistim.org–Thisfree-to-usecollaborative,searchablewikiofpublishedprimaryneuromodulationtherapyresearchwascreatedin2013asaresourcefortheglobalneuromodulationcommunitytoextendtheutilityofpublishedclinicalresearch.ThegoalsofWIKISTIMaretoimprovepatientcareandthequalityofresearchreports,fostereducationandcommunication,revealresearchneeds,andsupportthepracticeofevidence–basedmedicine.Pleasenote:Thisinformationshouldnotbeusedasasubstituteformedicaltreatmentandadvice.Alwaysconsultamedicalprofessionalaboutanyhealth-relatedquestionsorconcerns. References 1.MerckManual.(2014)ComplexRegionalPainSyndrome(CRPS).Availableat:http://www.merckmanuals.com/professional/neurologic-disorders/pain/complex-regional-pain-syndrome-crps(accessedJuly19,2016).2.NorthRBetal.Spinalcordstimulationversusre-operationinpatientswithfailedbacksurgerysyndrome:aninternationalmulticenterrandomizedcontrolledtrial(EVIDENCEStudy).Neuromodulation2011;14:330–6.3.BreivikH,CollettB,VentafriddaV,CohenR,GallacherD.SurveyofchronicpaininEurope:prevalence,impactondailylife,andtreatment.EurJPain.2006May;10(4):287-333.Epub2005Aug10.PubMedPMID:16095934.4.ZhuoM,WuG,WuLJ.Neuronalandmicroglialmechanismsofneuropathicpain.MolBrain.2011Jul30;4:31.Review.http://www.molecularbrain.com/content/4/1/31(accessedJuly17,2016).5.ZorowitzRD,SmoutRJ,GassawayJA,HornSD.Usageofpainmedicationsduringstrokerehabilitation:thePost-StrokeRehabilitationOutcomesProject(PSROP).TopStrokeRehabil.2005Fall;12(4):37-49.6.NICE.(2008)Spinalcordstimulationforchronicpainofneuropathicorischaemicorigin.Availableat:www.nice.org.uk/TA159(accessedJuly17,2016).7.KramesEetal.UsingtheSAFEprincipleswhenevaluatingelectricalstimulationtherapiesforthepainoffailedbacksurgerysyndrome.Neuromodulation2011;14:299–311.8.EkreOetal.Long-termeffectsofspinalcordstimulationandcoronaryarterybypassgraftingonqualityoflifeandsurvivalintheESBYstudy.EurHeartJ2002;23:1938–1945.9.DeerTR,MekhailN,ProvenzanoD,PopeJ,

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KramesE,LeongM,LevyRM,AbejonD,BuchserE,BurtonA,BuvanendranA,CandidoK,CarawayD,CousinsM,DeJongsteM,DiwanS,EldabeS,GatzinskyK,ForemanRD,HayekS,KimP,KinfeT,KlothD,KumarK,RizviS,LadSP,LiemL,LinderothB,MackeyS,McDowellG,McRobertsP,PoreeL,PragerJ,RasoL,RauckR,RussoM,SimpsonB,SlavinK,StaatsP,Stanton-HicksM,VerrillsP,WellingtonJ,WilliamsK,NorthR;NeuromodulationAppropriatenessConsensusCommittee.Theappropriateuseofneurostimulationofthespinalcordandperipheralnervoussystemforthetreatmentofchronicpainandischemicdiseases:theNeuromodulationAppropriatenessConsensusCommittee.Neuromodulation.2014Aug;17(6):515-50;discussion550.doi:10.1111/ner.12208.PubMedPMID:25112889.10.Medscape.(Jan.7,2015)SpinalCordStimulation.Availableat:http://emedicine.medscape.com/article/1980819-overview(accessedJuly18,2016).11.LiemL,RussoM,HuygenFJ,VanBuytenJP,SmetI,VerrillsP,CousinsM,BrookerC,LevyR,DeerT,KramerJ.One-yearoutcomesofspinalcordstimulationofthedorsalrootganglioninthetreatmentofchronicneuropathicpain.Neuromodulation.2015Jan;18(1):41-8;discussion48-9.doi:10.1111/ner.12228.Epub2014Aug21.PubMedPMID:25145467.12.Nguyen,JP,Nizard,J,Keravel,Y,Lefaucheur,JP.Invasivebrainstimulationforthetreatmentofneuropathicpain.NatRevNeurol.7,699–709(2011);publishedonline20September2011.13.JinDM,XuY,GengDF,YanTB(July2010).Effectoftranscutaneouselectricalnervestimulationonsymptomaticdiabeticperipheralneuropathy:ameta-analysisofrandomizedcontrolledtrials.DiabetesRes.Clin.Pract.89(1):10–5.14.AzharyH,FarooqMU,BhanushaliM,MajidA,KassabMY.Peripheralneuropathy:differentialdiagnosisandmanagement.AmFamPhysician(2010)Apr1;81(7):887-9215.TheFoundationforPeripheralNeuropathy.https://www.foundationforpn.org/what-is-peripheral-neuropathy/facts-risk-factors/.(accessedJuly17,2016)16.Baron,R.MechanismsofDisease:neuropathicpain—aclinicalperspective.NatureClinicalPracticeNeurology(2006)2,95-10617.UniversityofChicago,CenterforPeripheralNeuropathy.http://peripheralneuropathycenter.uchicago.edu/learnaboutpn/typesofpn/inflammatory/hiv_aids.shtml(accessedJuly17,2016).18.Rutchik,JS.(2011,Sept26).ToxicNeuropathy.MedscapeReference.Retrieved10/1/12fromhttp://emedicine.medscape.com/article/1175276-overview.19.KumarA,FelderhofC,EljamelMS.Spinalcordstimulationforthetreatmentofrefractoryunilaterallimbpainsyndromes.StereotactFunctNeurosurg81(1-4):70-74,2003.20.VallejoR,KramerJ,BenyaminR.Neuromodulationofthecervicalspinalcordinthetreatmentofchronicintractableneckandupperextremitypain:Acaseseriesandreviewoftheliterature.PainPhysician10(2):305-311,2007.21.ReverberiC,DarioA,BarolatG.Spinalcordstimulation(SCS)inconjunctionwithperipheralnervefieldstimulation(PNfS)forthetreatmentofcomplexpaininfailedbacksurgerysyndrome(FBSS).Neuromodulation.2013Jan-Feb;16(1):78-82;discussion83.doi:10.1111/j.1525-1403.2012.00497.x.Epub2012Sep17.PubMedPMID:22985076.22.NovakCB,MackinnonSE.Outcomefollowingimplantationofaperipheralnervestimulatorinpatientswithchronicnervepain.PlastReconstrSurg.2000May;105(6):1967-72.

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Neuropathy,NeuropathicPain,andPainfulPeripheralNeuropathy