PainPathways

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MedicalNeuroscience|Tutorial

PainPathways

MAPTONEUROSCIENCECORECONCEPTS1

NCC1. Thebrainisthebody'smostcomplexorgan.

NCC3. Geneticallydeterminedcircuitsarethefoundationofthenervoussystem.

NCC7. Thehumanbrainendowsuswithanaturalcuriositytounderstandhowtheworldworks.

NCC8. Fundamentaldiscoveriespromotehealthylivingandtreatmentofdisease.

LEARNINGOBJECTIVES

Afterstudyoftoday’slearning,thestudentwill:

1. Characterizetheorganizationoftheanterolateralsystemfromperipheralnerveendingtocerebralcortex.

2. Recognizecomponentsoftheanterolateralsysteminthespinalcord,brainstem,thalamusandcerebralcortex.2

3. Characterizetheorganizationofthetrigeminalpain&temperature(spinaltrigeminal)systemfromperipheralnerveendingtocerebralcortex.

4. Recognizecomponentsofthetrigeminalpain&temperature(spinaltrigeminal)systeminthebrainstem,thalamusandcerebralcortex.1

TUTORIALNARRATIVE

IntroductionTherearetwomajor,parallelsystemsthatconveysomaticsensoryinformationfromtheperipheryofthepost-cranialbodytothecortex,thedorsalcolumn-medial lemniscussystemandtheanterolateralsystem.Therearecomparableparallelsystemscarryinginformationfromthefaceassociatedwiththecentralprojectionsofthetrigeminalnerve. Inaddition,there isan importantsystemcarryingproprioceptive informationfromthemusclespindles to thecerebellum.This tutorialwill focuson thepathways takenby thecomponentsof thesystems for transmissionof neural signals pertaining to pain and temperature sensation. It is important foryourunderstandingofneurologicaldeficitsseenintheclinictoknowwherethesepathwaystravelrelativetoeachotherandtootherstructures(includingthecranialnervenuclei)inthebrain.

1 VisitBrainFacts.orgforNeuroscienceCoreConcepts(©2012SocietyforNeuroscience)thatofferfundamentalprinciplesaboutthebrainandnervoussystem,themostcomplexlivingstructureknownintheuniverse.

2 Asyoustudysomaticsensorypathways,youshouldbeginreferringtocrosssectionsthroughthenervoussystem(e.g.,inSylvius4)sothatyoucanrecognizewhererelevantnucleiandaxonaltractsarelocatedwithinthebrainandspinalcord.

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Pathwaysmediatingpainandtemperaturesensation.

Theanterolateralsystem is responsibleforconveying informationaboutpain,temperatureandcrudetouch(i.e.,touchlackingthespatialresolutionofthedorsalcolumnsystem)fromthepost-cranialbody.Comparableinformationabout the face isprocessed in trigeminalpathways. Thesepathwaysare illustrated inFigures 1and2.Mostperipheralprocessesassociatedwiththedorsalrootganglioncellsthatcontributetothissystemare“free.”Thatis,theyarenotassociatedwithencapsulatedendingslikethoseinthedorsalcolumn-mediallemniscal system. In addition, the first-order fibers associated with the anterolateral system are generallymuch smaller indiameter than thoseassociatedwith thedorsal columnsystem. (Sowhatdoes this tell youabouttherelativeconductionvelocitiesofthesetwoimportantsomaticsensorypathways?)

Thefirst-orderneurons intheanterolateralsystem, likethoseinthedorsalcolumn-medial lemniscalsystem,havetheircellbodiesinthedorsalrootganglia.Thecentralprocessesoftheseneuronsterminateonsecond-orderneuronsinthedorsalhornofthespinalcord.Painandtemperatureinformationfromreceptorsinthefaceiscarriedintothebrainonthefifthnerve.Thecellbodiesofthefirstorderneuronsareinthetrigeminalganglionandthecentralprocessesofthecellsmakesynapsesinanucleusinthemedullaknownasthespinaltrigeminalnucleus (of the fifthnerve).Thisnucleus isactuallycontinuouswiththedorsalhornof thespinalcord.

Thesecond-orderneuronsinthedorsalhornofthespinalcordsendtheiraxonsacrossthemidline,wheretheyaccumulateintheanterolateral(ventrolateral)partofthewhitematter.Theyascendinthislocationthroughthe length of the cord.Many of these fibers continue through themedulla, the pons and themidbrain tocontact third-order neurons in theventral posterior lateral (VPL) nucleusof the thalamus (aswell as otherthalamicnuclei).Thisdirectpathway fromthespinal cord to the thalamus isoftencalled thespinothalamictract.Actually,thethalamusisonlyoneofthetargetsofthesecond-orderneuronsintheanterolateralsystem.These neurons also project to central parts of the medulla, pons and midbrain known collectively as thereticularformation(thiscomponentoftheanterolateralsystemisknownasthe“spinoreticulartract”)andtothe periaqueductal gray matter and the superior colliculus (this component is known as the“spinomesencephalictract”).Second-orderneurons located inthespinal trigeminalnucleussendtheiraxonsacrossthemidlinetoformtheventraltrigeminothalamictract,whichtravelstotheventralposteriormedial(VPM)nucleusofthethalamus.

Third-orderneuronsintheventralposteriornucleusandinotherthalamicnucleithenprojecttothecortexviathe internal capsule.Thepostcentral gyrusappears tobe important for theability todiscriminate theexactlocationofpainfulstimuli,butmanyother,lesswell-understoodcorticalareas(includingareasintheanteriorpartofthecingulategyrus)appeartobeimportantinthecompletesensationofpain, includingthecomplexaffectivedimensionsofpain.

Figure 3 presents a diagram of the major parallel pathways carrying somatic sensory information to thecerebralcortex(seetutorialnoteson“MechanosensoryPathways”).ThepathwaysformechanoreceptionandthepathwaysforpainandtemperaturesensationshowninFigureA1areshowntogetherbilaterally.

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Figure1.Organizationofthecentralpathwaysforpainandtemperaturesensation.Thesepathwaysalsocarrycrudeinformationabouttouch.(Asdiscussedanearliertutorial,thereisasmallinputintothetrigeminalnucleifromtheseventh,ninthandtenthnerves,butthisinputisoflittlesignificanceclinically.)(IllustrationbyN.B.Cant)

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Figure 2. Location of the anterolateral system in the cervical cord and brainstem, with the ventraltrigeminothalamictract,asseenincross-sections.Notethatatalllevels,thefibersofbothtractsarelocatedintheanterolateralpartofthebrainstemtegmentum(second-orderneuronsare illustrated inwhite).(SectionsfromSylvius4)(Figurecontinuedonnextpage)

Dorsalhorn

AnterolateralsystemCervicalspinalcord

Caudalmedulla

Anterolateralsystem

Spinaltrigeminalnucleus

Spinaltrigeminal

tract

Anterolateralsystem

Middlemedulla

Spinaltrigeminaltract

Spinaltrigeminalnucleus

Regionofventraltrigeminothalamictract

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Anterolateralsystem

Caudalpons

Spinaltrigeminalnucleus&tractRegionofventral

trigeminothalamictract

Midbrain Anterolateralsystem

Regionofventraltrigeminothalamictract

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Figure3.Adiagramofthemajorparallelpathwayscarryingsomaticsensoryinformationtothecerebralcortex.Thepathwaysformechanoreceptionandthepathwaysforpainandtemperaturesensationareshowntogetherbilaterallyinthisfigure.Seerelatedfigureslabelsofnucleiandtracts.(IllustrationbyN.B.Cant)

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Pathwaysforpain,temperatureandacrudesenseoftouch.

Pathway Receptors First-orderneurons

Second-orderneurons Third-orderneurons Primarycorticalarea Decussation

patternanterolateralsystems

(forpostcranialbody,includingtheposteriorportionofthehead)

[seeFigures10.6Aand10.5]

freenerveendingsinsomatictissuesand

viscera

ipsilateraliDRGs

(dorsalrootganglionneurons)

Aδ&Cafferentfibers

ipsilateraldorsalhornofspinalcord:

• superficiallaminae(marginalzoneandsubstantiagelatinosa)

• deeperlaminaeatbaseofdorsalhorn

firstpainpathway:contralateralventralposteriorcomplexofthethalamus:

• ventralposteriorlateral(VPL)nucleus

secondpainpathways:contralateraltargetsinbrainstemandthalamus:

• reticularformation(spinoreticulartract)

• periaqueductalgray(spinomesencephalictract)

• nucleusofthesolitarytract

• intralaminarthalamicnuclei

firstpainpathway:contralateralS1

Brodmann’sAreas3,1&2

• lowerextremityisrepresentedintheparacentrallobule

• upperextremityisrepresentedintheΩ-shapedsegmentofthepostcentralgyrusnearthemiddleofthecentralsuclus

• nociceptivestimuliarelocalizedviathesomatotopicrepresentationsinS1

secondpainpathways:contralateralanteriorcingulategyrus,insula,orbital-medialprefrontalcortex,amygdala,

hypothalamus(componentsofthe“limbicforebrain”thatprocess

affectivesignals)

spinalcord:second-orderaxonsofdorsalhornneuronscrossthemidlineintheventralwhite

commissurenearthesegmentoforiginandascendtheneuraxisasthe

spinothalamictractandvarious

componentsoftheanterolateralsystemthatterminateinthe

brainstem

spinaltrigeminalsystem

(forface—anteriorthirdofhead)

[seeFigure10.6Band10.5]

freenerveendingsinsomatictissuesand

viscera

ipsilateraltrigeminalganglionneuronsintrigeminal(gasserian)

ganglion

ipsilateralspinalnucleusofthe

trigeminalcomplexinthedorsal-lateralpons(caudal)andmedulla

firstpainpathway:contralateralventral

posteriorcomplexofthethalamus:

• ventralposteriormedial(VPM)nucleus

secondpainpathway:contralateraltargetsinbrainstemandthalamus

(sameasabove)

firstpain:contralateralS1Brodmann’sAreas3,1&2

• faceisrepresentedintheinferiorsegmentofthepostcentralgyrus

• nociceptivestimuliarecrudelylocalizedviathesomatotopicrepresentationsinS1

secondpain:contralateralcomponentsofthe“limbicsystem”

(sameasabove)

ponsandmedulla:second-orderaxonsofthespinalnucleuscrossthemidlineandascendthebrainstemasthetrigemino-

thalamictract,whichoccupiesapositionnearthefibersoftheanterolateralsystem

dorsalcolumnvisceralpainpathwayii(seeBox10C)

freenerveendingsinviscera

ipsilateralDRGs ipsilateralintermediategrayofspinalcord(near

centralcanal)

ipsilateraldorsalcolumnnucleiiii:

• gracilenucleus• cuneatenucleus

contralateralinsulasuppliedbyafourth-orderrelayintheventral

posteriorcomplexofthethalamus(differentpartthanVPL)

caudalmedulla:internalarcuate

fibersthatgiverisetomediallemniscus

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i InthisTable,thetermsipsilateralandcontralateralwillrefertothesideoftheperipheralorcentralnervoussystemrelativetothelocationofthesensoryreceptors;e.g.,

corticalrepresentationoffirstpainconveyedviaAδaxonsoccursinthecontralateralprimarysomaticsensorycortex.ii Thisnewlydiscoveredpathwayprocessesvisceralpainsignalsderivedfromthoracicandabdominalviscerainparallelwithprojectionsthatcontributetotheanterolateral

system(e.g.,thevisceralpainsignalsthatareconveyedviaanterolateralsystemaxonstothecaudalpartofthenucleusofthesolitarytract).iii Visceralpainsignalsmaybeprocessedbydifferentneuronsinthedorsalcolumnnucleithanthosethatrespondtolight,discriminativetouch.However,theremaybesome

dorsalcolumnneuronsthatreceivebothvisceralandnon-visceralsignals;theseneuronscouldalsoprovideaneuralsubstrateforreferredpainsensations,inadditiontothemechanismthatisusuallydescribedinthedorsalhornofthespinalcord(seeBox10B).