Pain from brain: Can we remodel neural circuitry that generates phantom limb pain and other forms of neuropathic pain?
Thomas Elbert
∗UniversityofKonstanz,DepartmentofPsychology,Germany
Fromoccasionalstabbingtoexcruciatingpain,asthoughthelimbis setonfire:NobodyhadinformedCorporalPaboutphantomlimb sensationswhenhisrightlowerarmwasamputatedfollowinga blastinAfghanistan.AtfirstMr.Pwassurprisedthathecouldstill feelhisrightfingersandhandformonthsaftertheamputation.
Butthenherealizedthatthebrainstructuresthatarerelatedtothe feeling,movementandpaininhisarmwouldstillexistafterampu- tation.Coulditbethattheneuralsubstratethathadoncecontrolled theperceptionandmovementofhisarmwerenowgivingriseto phantomlimbsensations?Overthecourseoftheyearsfollowing hisamputation,theveteranstartedtofeelasifhishandwasmoving higherup,asifitweredirectlyconnectedtothestump.Thephan- tomsensationsofhisforearmwerenolongerthere andslowly, overtime,hebegantofeelpaininhisnow-absenthand.Atfirstthe painappearedonlyoccasionally,butsubsequently,thetinglingand sharppainthatoccurredatpreciselocationsonhisphantomhand becamemorefrequentwitheachpassingyear.Thepain,although nowan“illusion”tohim,wasmoredevastatingthanany“real”pain, resultingfromthestimulationofnociceptors.Whenheformeda fistwithhisphantomfingers,theflexionwouldnotstop,untilhe wouldfeelhowhisfingernails,slowly,penetratedthepalm.
ThereportofThomasWeiss,CarolineDietrich,WolfgangMilt- nerandcolleaguesfromtheUniversityofJena [1]inthisissue, demonstrateshowtouseknowledgefrombehaviouralandneuro- sciencetodeveloptreatmentforthisclinicalcondition.
Somatosensoryinformationisconveyedfromthebody’ssurface tothesomatosensorycortexandfromthere,itisrelayedtoadjacent neuralnetworks.Subsequentactivityofso-called“hiddenunits”is determinedbytheactivitiesoftherepresentationalinputunitsand theweightsontheconnectionsbetweentheinputandthehidden units.Hence,hiddenunitsconstructtheirownrepresentationsof theinputandthusloosethespatialhomuncularordering.There- fore,theorganizationoftheselayersisnotaccessiblebycurrent formsofbrainimaging–interactingwithstimulusandresponse representation,theselayersrepresentspaceforself-organization and“freedom”.Theweightsbetweentheinputandhiddenunits determinetheextenttowhichhiddenlayersbecomeactive.Neu- ralconnectivityandthusinformationcodingbythesehiddenlayers
∗Tel.:+497531884609;fax:+497531884601.
E-mailaddress:Thomas.Elbert@Uni-Konstanz.de
remainflexiblethroughoutlife.Thebehaviouroftheoutputunits– andthismayormaynotincludeasignalforpain– dependsonthe activityofthehiddenlayersandtheweightsbetweenthehidden andtheoutputunits.Ifthesensoryinputfromabodyparttoits brainrepresentationhadbeenseveredbydamage,therespective areaofthebrainwillnotliedormantbutadaptstosuchinterrup- tionsofnormalfunctioningbymeansofreorganizationandplastic alterations.Evidencefromanimalandhumanstudiessuggestthat amputationordisuseofalimbleadstoaninvasionofadjacentcor- ticalzonesintotheoneformerlyrepresentingtheamputatedlimb [1–3,5–7].
Atthesametime,increaseduseoftheremaininglimbleadsto anexpansionofitscorticalrepresentationandwithittoincreased dexterity.Bymeansofpractice,forexample,onecanacquireacom- plexmotortask,suchasplayingtheviolin,whichinvolvesquick movementsofthefingers.Inordertoperformwiththecorrespond- ingneeds,thebrainisabletoalteritscircuitry,anditdoessowith additionalpractice[2,4].Thus,thereisnever anyportionofthe brain,whichgoesunused;therewillbeno“unusedspace”.Abrain region,disconnectedfromitsoriginalinput,willnotstayinactive forlong.Thenervecellsfromtheinactivepartofthebrainbecome rapidlyinvolvedintheactivitythatisgoingoninneighboringareas [2].Correspondingly,wecanobservetwosuchchangestobecome evidentinthebrainofpersonswithanupperarmamputation:
(1)Theareaofthebrainthatisresponsiblefortheintactarmisused moreoftenandwithincreasingskillfulnessmustprocessmore informationthanusual.Thereforethisareabecomesenlarged.
(2)Thebrainstructuresthathadprocessedinformationfromthe nowamputatedarmshouldalsoshowreorganization[4].
There are various relationships between these neuroplastic eventsandthesubjectivephantomphenomena[7].Morethanhalf ofcaseslikeCorporalPwillreportstrongphantomlimbpain,andin thesetheremodelingofthesomatosensorybrainareasisextreme.
Areasthatwereoriginallyresponsibleforahandandfingerswere seentoprocessinformationfromtheliporface[2,6,7].However, asmentionedabove,wecanproperlyimageonlythe“input”and
“output”layersofcortex,whichmirrorwiththeirhomuncularorga- nizationthearrangementofthereceptorsintheperiphery–wedo notyetknowhowtodecodetheinformationinthe“hidden”lay- ersofthisgargantuanassociativenetworkhousedinthecerebral
Konstanzer Online-Publikations-System (KOPS) URL: http://nbn-resolving.de/urn:nbn:de:bsz:352-226278 Erschienen in: Neuroscience Letters ; 507 (2012), 2. - S. 95-96
https://dx.doi.org/10.1016/j.neulet.2011.12.004
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cortex.Wealsohavenotyetstudiedtheroleofthecerebellumin theseplasticalterations.
While continuousplastic reorganization of neuralstructures enablesthecentralnervoussystemcircuitrytoconformtothecur- rentneedsofanorganismandthususuallywouldconferanobvious adaptiveadvantage,plasticitybearstheriskformaladaptivereor- ganization. This is obviously the case for phantom-limb pain.
Similarprocessesmayresultinotherformsofneuropathicpain oritching.Thevariedsusceptibilitytodevelopingpost-therapeutic neuralgiaafteranattackofshingles,forinstance,mayberelated tothereorganizationalCNSprocessestriggeredbyoneorseveral shinglesepisodes.Anyalterationstotheafferentinput,beitatthe leveloftheperipheralnerve,thedorsalrootganglionordorsalroot, orthecentralnervoussystemcanthusleadtomaladaptivepain.
Treatmentsof thisconditions haveincludedrelaxationtech- niques, massage therapy to the residual limb, biofeedback, meditation, acupuncture, neuro-stimulators, physical therapy, behaviourtherapyandcounselingandtheadministrationofvari- ousdrugs.Despiteisolatedreportsofsuccess(forreviewsee,e.g.
[7]),notreatmenthasbeenbeneficialonmorethanatemporary basis.
Since bottom-up mechanisms apparently underlie both the corticaldisorderand thephantom-limb pain, it seemspossible thatabehaviouralinterventioncouldbeofvalueinreducingor eliminatingphantompain. Dietrichand colleaguesinthis issue reporttesting whetherthey canreverse someof these reorga- nizationalprocesses by motivatingand training thepatientsto frequentlyusetheirstumpand prothesis in a more systematic manner,particularlyinbehaviorallyrelevanttasks.Accordingto theuse-dependentchangesindicatedabove,someoftheplastic alterationsmaybeerasedandwithit,thephantompainmaysub- side.TheJenaresearchersemployedprocedures derivedinpart fromatherapy,termedconstraint-induced(CI)movementtherapy, developedbyTaubandco-workersthathasbeenfoundtobeeffec- tiveinsubstantiallyimprovingtherehabilitationafterCNS-injury [8].Followingthislogic,Dietrich,Weiszandcolleaguesintroduced thetrainingofuseofaprosthesiswithsomatosensoryfeedback.
Asopposedtotheheuristictreatmentattemptsmentionedabove, this innovativeapproach hasbeenbased ontheoreticalknowl- edgederivedfrombasicresearchinbehaviouralpsychologyand theneurosciences.
Asin CI movement therapy, the authors administered two- weeks ofmassed practicein theuseofa hand prosthesiswith somatosensory feedback on grip strength. The strength was detectedbypressuresensorslocatedinthebendbetweenthumb andindexfingeroftheprosthetichandandfedbackthrougheight electrodestotheskinofsubject’sstump.Thisprocedurewould reinstateameaningfulfeedbackofhandusetothesomatosensory cortexinbehaviorallyrelevanttasks,i.e.,duringprosthetichand use.Theoutcomeshowedtheexpectedincreaseinfunctionality andwithitadecreaseinphantomlimbpain.Whiletheauthors didnotmonitorchangesincorticalorganization,previousresearch stronglywouldsuggestthatsuchanalterationhasoccurred[2].
Thesechangesmaybelastinguntilanotherbehaviorallyrelevant taskengagestheplasticprocessestoremodelthecorticalmachin- eryyetanothertime.
Theauthorsdemonstratesfeasibilityoftheprocedureandshow thattreatmentofphantomlimbpainmaybeareachablegoal,given that a two-week training is already sufficient toproduceclini- callyrelevantimprovement.Whilethesamplesizewassmalland thestudycannotdismantlewhatultimatelymayhavecausedthe observedchanges,thereportoffershopeforthoseinpain.
References
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