Medical Neuroscience Tutorial - Duke University
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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).
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