内侧丘脑和额叶皮层在痛觉调制和针刺镇痛中的整合作用

内侧丘脑和额叶皮层在痛觉调制和针刺镇痛中的整合作用 内侧丘脑和额叶皮层在痛觉调制和针刺镇 痛中的整合作用 针刺研究1997年第1—2期l5? Itwasfoundthatelectmacupuncture(EA1at"Zusanli"and"Huantiao"pointsorelec— tricalstimulatingtheprecruciatecortexandsomatosensoryareaIIcouldinhibitthenocicep— tireresponsesofCMneurons.AfterbilateralelectmlylielesionoftheheadportionofCdthe inhibitoryeffectofEAofstimulatingtheprecruciatecortexwasobviouslyreduced,whilethat ofelectricalstimulatingSI1wasnotnoticeablyaffectedinmostCMneuronsrecorded.Topical applicationofglutamate(Glu)atsensorimotorareaI(SmI)exhibitedremakableinhibitionon nociceptiveresponsesofPfneuronsintherat.whichwassimilartOtheinhibitoryeffectof EA.FollowingbilaterallesionoftheheadportionofCdcausedbymicroinjectionofkainic acid,theinhibitionpmducedbyGluappliedatSm1wasabolished,andEAdidnotexertob— viousinhibitiononthenociceptiverespou~s.LesiondCdmadebymieroinjectionofkainic acidandbyelectrolysisyieldedsimilarresuhsshowingtheabolishmentofinhibitoryeffectsof EA FromtheresultsobtaineditisindicatedthatCdisanintermediatelink.viawhichthe precruciatecortexorSm1exertsdescendingmodulationonneuronsinthalamieILNinAA However,itmaynotbe tionofILN /一f Iemanating 润descending山 5现田 4.内侧丘脑和额叶皮层在痛觉调制 和针刺镇痛中的整合作用,尺形 . 2 虚垫盟袁斌张玉秋张笋堑—查吕方王跃秀 (西安医科太学神经生理研究室,西安710061) 根据以往解剖学和电生理学的研究,我们提出了一个新的研究假设,即内侧丘脑中央 下核(Sin)和前额叶腹外侧眶皮层(vIo)不仅参与痛觉感受而且也可能参与痛觉调制,脊 髓一Sm—VLO-PAG(导水管周围灰质).脊髓可能构成一个痛觉调制的负反馈环路,外周的 或局部的激活该系统的活动,通过脑干下行抑制系统在脊髓/三叉水平调制伤害感受性输 入;针刺兴奋细纤维的传人信息经脊髓/延髓到达Sm,并上行到VLO和体感皮层,以产 生针感,又经VLO激活PAG一脑干下行抑制系统,以产生镇痛.研究结果总结如下: 1.Sm和VLO参与痛觉调制 (1)电解损毁单侧Sm对大鼠甩尾(TF)反射无明显影响,但损毁双侧Sm后,明显易 化TF反射,甩尾潜伏期(TFL)减小,提示Sm参与痛觉下行调制并具有紧张性抑制作用. (2)电刺激单侧Sm可明显抑制大鼠TF反射,TFL明显延长,这种抑制效应可被电 解损毁同侧VLO或双侧PAG的腹外侧都完全阻断;电刺激内侧丘脑Sm周围其它核团 对TF反射无抑制作用.本结果 表 关于同志近三年现实表现材料材料类招标技术评分表图表与交易pdf视力表打印pdf用图表说话 pdf 明,电刺激Sm产生的镇痛作用是通过VLO转而激括 PAG下行抑制系统,在脊髓水平调制伤害感受性输入而实现的;Sm可能是内侧丘脑一个 针刺研究I997年第12期 仅有的痛觉调制中枢. (3)电刺激单侧VLO亦可抑制TF反射,并且随刺激强度或串长的增加而加强,但 发现在停止VL0刺激后的5—1O秒内有后易化效应.损毁双侧PAG可完全阻断VlO 诱发的效应. (4)单侧Sm或VLO内微量注射谷氨酸钠(glutamate,Glu,200mmol/L,0.5/l1)明显 抑制大鼠TF反射,单侧VLO内微量注射7一氨基丁酸(GABA100mmol/L,0.7/l1) 取消 Sm诱发的抑制,双侧PAG的腹外侧部微量注射GABA(每侧0.5p1)可取消Sm和VLO 产生的抑制,双侧VLO内微量注射GABA易化TF反射.本结果与上述电刺激和电损毁 所得结果一致,并且表明,电刺激Sm,VLO产生的镇痛作用是由于激活了Sm或VLO内 的神经元胞体而不是过路纤维,损毁产生的阻断效应是由于破坏了其中的神经元活动而 引起的;本研究还证明VL0也具有紧张性下行抑制作用. (5)电刺激同侧或对侧Sm可明显抑制脊髓背角WDR和NS神经元的伤害性反应 并且这种效应随刺激强度或串长的增加而增强,但刺激内侧丘脑其它核团无明显抑制效 应.本研究结果为Sm参与痛觉调制提供了电生理学的证据,并且表明电刺激Sm或 VLO对运动反射的抑制是作用于背角伤害感受性的传人部分而不是传出部分. (6)电刺激Sin或VLO抑制大鼠张颌反射(JOR),刺激牙髓诱发的二腹肌肌电 (dEMG)幅度明显降低,其抑制的阈值很低(20vA),并随刺激强度的增加而增强,电解损 毁VLO或PAG可明显减弱或取消对JOR的抑制效应.结果表明,Sm参与头面部的痛 觉调制,并且这一作用是通过VLO.PAG通路,进而激活脑于下行抑制系统,在三叉水平 调制伤害感受性输入而实现的,为Sm,VLO参与痛觉调制提供了进一步的证据. 2.Sm和VLO参与针刺镇痛 (1)针刺可激活大鼠Sm神经元的活动,一般对伤害性刺激反应的神经元也对针刺 发生反应,未发现对非伤害性刺激反应的神经元;电刺激腓神经同时 记录 混凝土 养护记录下载土方回填监理旁站记录免费下载集备记录下载集备记录下载集备记录下载 复合动作电位, 发现引起c波的阈刺激强度(O.2—0.5mA,0.3ms)能激活Sm神经元的活动,且随着刺激 强度的增加而增强,阈下刺激则无反应,电刺激"足三里"穴亦有类似的反应,但引起Sm 神经元反应的强度阈值大约是刺激腓神经的10倍(2.0—4.0mA),提示针刺具有伤害性 刺激的属性,针刺兴奋细纤维的传人信息可上行到达Sm并可能产生针感和镇痛效应. (2)电解损毁双侧Sm或VLO可明显减弱强电针(5.0mA)刺激对大鼠TF反射的抑 制效应,而对弱电针(0.5mA)的镇痛效应无明显影响;双侧Sm内微量注射局部麻醉剂 (1idocaine),亦可明显减弱强电针刺激对大鼠脊髓背角伤害感受性神经元的抑制效应,丽 对弱电针的镇痛效应无明显影响.提示针刺兴奋细纤维产生的镇痛效应是通过激活Sm VLO,进而激活PAG.脑千下行抑制系统负反馈地在脊髓水平调制伤害感受性传递而实 现的. 本研究的发现,基本上证明了上述的研究假设,它是前一丘脑水平痛觉调制及针刺镇 痛研究领域内的一个重要进展,有重要的理论意义. *车研究属国家自然科学基金资助项目{No39470870) 1延安医学院生理教研室2西安交通大学生物工程系生理教研室 .一 针刺研究1997年第1—2期17? 4.IntegrativeRoleofThalamicNucleusSubmedius andVentrolateralOrbitalCortexinNociceptive ModulationandAcupunctureAnalgesia(Review) TangJtngshi,YuanBin,ZhangYuqin,ZhangSan, YangJieI,LuFang2,WangYuexlu (ResearchLaboratoryD厂Neurophysiology,Xi'allMedicalUniversity,Xi'an,710061) Onthebasisoftheanatomicandneurophysiologiealstudiesoilthethalamicnucleussub— medius(Sm)andthefrontalvantrolateralorbitalcortex(VLO),anewhypothesiswas.sug— gestedthattheSmandVLOarenotonlyinvolvedinnociceptionbutalsoinnocieeptivemod— ulation;anegativefeedbackloopresponsiblefornoclceptivemodulationconsistsofthespinal cord?SrVLoPAG?spinalcordinwhichperipherallyorlocallyevoked-act{va-t~.onoftheSm mayresultinactivationofthebrainstemdescendinginhibitorysystemviaVLOforwardto thePAGandinhibtionofthenociceptireinputsatthespinaland/orWigeminallevel;this loopmayplayanimport~troleinsensationandanalgesiaelicitedbyacupuncture— activating thesmallafferentfibersintheacupoints,i.e.,theafferentinforraationselicitedbyacupunc? ture.activationofthesmallfibers(?,?groups)viathe~inalcordreachSm,andascendto VLOandcerebralcortexsomatosensoryarea(SI,II)toproduoeacupuncturesensation, and,ontheotherhand,deseendinglyactivatetheFAG— brainstemdescemnginhibitorys~tem anddepressthenociceptiveinputsatthespinaL/trigeminalleveltoproduceanalgesia.Results obtainedfromthisstudyaresuramarizedas.foIlows:, 1.SmandVLOparticipateinnocieeptivemodulation, (1)ElectrolyticlesionoftheunilateralSmdidnotinfluencetheTFreflex,butbilatera1 lesionssignificantlyfacilitatetheTFreflexwithanincreaseinthetailflicklatency(TFL), suggestingthattheSmisinvolvedinnociceptivemodulationandexertadescendingtomcin. hibitoryaction. (2)TheTFreflexismarkedlydepressedbyaunilateralelectricalstimulationofSmwith increasingTFLs.Th;sinhibitoryeffect,however,iscompletelyblockedbyelectrolyticlesions oftheipsilateralVLOorbilateralventrolatera1partsofPAG.ItiafoundthatelectrieaIstimu— lationofotherstructuresadjacenttoSminthemedialthelamusdoesnotsignificantlyinflu— e【IoetheTFreflex.Theseresultssuggestthattheantinociceptionproducedbyelectricalstim. ulationofSmismediatedbyVLOleadingtoactivationofthebrainstemdescendinginhibito— rysystemviaPAGanddepre~ionofthenociceptivetransmissionatthespinallevel,andthat 18?针刺研究1997年第12期 theSmmaybetheonlypainmodulatingcenterintheventromedialthalamus. (3)TheinhibitoryeffectsonTFreflexcanbealsoproducedbyelectricalstimulationde一, liveredtotheunilateralVLO.butafacilitstoryeffectoOCtlrsatashortperiodof5—10satter terrninatiouoftheVLostimulation.TheVLO-evokedinhibitionandafter— facilitationofTF reflexareblockedbyelectrolytic1esionsofthebilateralPAG (4)Microinjectionofglutamate(Glu,2()0ramol/L,0.51)unilaterallyintoSmorVLO significantlydepressestheTFreflex.withtheTFLsincreaseforover30rain.TheSm-evoked inhibition,however,isblockedbyipsilateralVLOinjectionofr-amlnobutyricacid(GABA, 100mmol/L,07"1)andtheSm—andVIO—evokedinhibitionsareblockedbyapplyingbi— laterallytheGABA(05?1oneachside)intoPAG.ItisfoundthatinjectionsofGABAin bilatera1VI0facilitatetheTFreflexwithdecreasingTFLs.Theseresultsareconsistentwith thoseobtainedformtheelectricalstimulationsandelectrolyticlesions,andsuggestthatthe analgesiaelicitedbyelectriealstimulationofSmorVLOisduetoactivationofthe1ocalcell bodyratherthanthepassingfibers,andtheblockingeffectselicitedbyelectmlytlclesionsape duetodisruptionoftheloca1neuronalactivities.ThisstudyalsodemonstratedthatthevJ existsadescendingtonicinhibitoryaction. (5)IpsilateralorcontralateralelectricalstimulationoftheSmsignificantlydepressesthe nocicepriveresponsesofneurons(WDRandNS)inthespina1dorsalhorntothestimulation? deliveredtotheperiphera]receptivefield.TheinhibitoryeffectselicitedbySmstimulationel— evatewithincreaseinthestimulationintensityortrainlength.However,electricalstimulation ofotherstrnauturesadjacenttoSminthemedialthalamusdoesnotsignificantlyin—fluence thenociceptiveTesponsesofthespinaldorsalneurons.Resultsofthisstudyprovidetheelec— tmphysiologicalsupportforSminvolvedinmodulationofnociception,andsuggestthatthe inhibitionofmovementreflexelicitedbyelectricalstimulationofSmorVLOisduetoinhibi— tionofthenociceptiveinputsbutnotoutputsatthespinalleve1. (6)Theinhibitionoftheratjaw—openingreflex(JOR)canbeproducedbyelectrical stinmlationofSmorVI,()withadecreaseinthemagnltudeofmodigastricuselectromyo一' gram(dEMG)evokedbydentalpulpstimulation,andhasalowerintensitythreshold (20? A).Thisinhibitondevatewithincreasingthestimulationintensity.Furthermore,thein?' hibitoryeffectsonJORelicitedbySmorVLOstimulationarecompletelyblockedbydec? trolyticlesionsofVLOorPAG.TheseresultssuggestthattheSmisinvolvedinmodulation oftheorofacialnociceptlon,andthisinhibitoryeffectismediatedbyVLOleadingtoactiva? tionofthePAG-bralustemdescendinginhibitorysystemanddepressionofthenociceptivein— putsatthetrigemlnalleve1.Therefore,resultsobtainedfromthisstudyprovidefurtherevi— dencefortheroleplayedbytheSmandVLOinmodulationofnociception. 2.SmandVL0participateinacupunctureanalgesia (1)Traditiona1needlingstimulationoftheacupointcanactivatenlostoftheneuronsin theratSm.Ingeneral,neuronsinSmexcitedbyacupuncturearealsoexcitedbynoxious 针刺研究1997年第1—2期 stimuliandthoseinhibitedareinhibited:Noneuronsarefoundrespondingtoinnocuousstiro— ulation;Byelectricalstimulationoftheperoneousnervewithrecordingthecommonaction potentia1.itisfoundthatthsSmneuronscanbeactivatedonlywhenthestimulationintensity increasestothethresholdforexcitingthdC一{ibers(C—wave)(0.2—0.4mA,0.3ms),and theneuronalrespons6sincreasewithincreasingthestimulationintensityandpulsenumbers; electricalstimulationofthereceptivefield(Zusanlipoint)byinsertingapairofneedleelec— trodeintothehindlegcanalsoactivatedtheSmneurons,butthisthresh61dofstimulationre— quiredforproducingtheneuronalresponsesisabout10times(3.0—40mA)ofthatof stimulationoftheperoneousnerve.Theseresultssuggestthattheacupuncturenatureisthe sameasthatofnnoieeptivestimulation,andtheafferentinformationselieitedbyC— fiberexci rationcainascendinglyreachtheSrowheretheneedlingsensationandanalgesiamaybepro— duced (2)Theanalgesiaprodueedb~ntensiveelectroacupuncture(5.0mA)stimulation (EAS)issignificantlyattenuatedbybdateralelectrolyticlesionsoftheSroorVLO,butthat producedbyweekEAS(0.5mA)isnotinfluenced:microinjectionsofLidocaineintotheSm eitherbilateralorunilateralalsosignificantlyattenuatetheinhibitoryeffectsproducedbYin— tensiveEAS(6.0mA)onthenocieeptiveresponsesofthespinaldorsalneurons(WDRand NS),butnotalterthosebyweekEAS(1.0roA)Theseresultssuggestthattheanalgesia producedbyacupuncture—evokedactivationofthesmallfiber(C— fiber)afferentmaybemedi— atedbySroleadingtoactivationofthePAG—brainstemdescendinginhibitorysystemviathe VLOanddepressionofthenocieeptivetransmissionatthespinalcordleve1. Findingsofthisstudyconfirmthehypothesismentionedabove,andsuggestthatapo— tentiaIroleofthemedialthalalllusandfrontaIcortexinnocieeptivemodulationandaeupune. tureanalgesia.Furtherstudiesinthisfieldmaybeofimportantsignificance. 5.氟哌啶增强电针镇痛时大鼠脑内 微透析液中单胺类递质的变化 束崇斌李晓艳朱燕华吴根诚许绍芬 (上海医科大学医学神经生物学国家重点实验室,上海200032) 本文采用大鼠脑内微透析及高教液相色谱电化学联检技术,观察多巴胺(DA)受体 拮 抗剂氟哌啶(DRO)加强电针(EA)镇痛时大鼠脑内微透析液中单胺类递质的变化,从而探 讨药物加强针刺镇痛的机制结果显示,EA后DA及其代谢产物高香草酸(HVA)在透 析液中含量增加(P<0.05或0.01),DRO与EA台用(DRO+EA)后,二者的含量较单用