针刺镇痛研究40年回顾北京大学神经科学研究所韩济生历史回顾•1958年出现了“针刺麻醉”新事物•周总理通过卫生部指示:研究针麻原理•全国100余座医学院校参与研究•1965年9月我接受国家任务主持此项目,至今40年•回顾40年历程,从科研方向、方法、结果进行总结,可能有一定意义•从“是什么”What?针刺真的镇痛吗?•到“为什么”Why?针刺为什么会镇痛?Acupucture-inducedanalgesiaHumanObservation:020406080-20020406080100120*AcupunctureatHekupointPainthresholdchange(%)Timeinminutesneedlemanipulation(n=66)controlgroup(n=22)7足三里合谷穴对照组合谷优于足三里合谷-足三里合谷穴对照组合谷-足三里双穴优于单穴对照组合谷穴非经穴针刺非经穴也有镇痛效果合谷穴Sitespecificity•Meridine/channel(morphologicalevidence?)•Acupoints(precisetommlevel?)•Bodypoints(Chineseoriginal)orEarpoints(Frenchscholars)•Bio-electricallysensitivesites,ordenselyinnervatedsites•relativeratherthanabsolutespecificity12痛阈变化百分数14留针留针捻针捻针耳针镇痛:规律相似捻针有效,留针效差同一天重复电针不同天重复电针电针镇痛有个体差异,具有可重复性大鼠实验测痛是否能预测针麻效果?外科手术时针麻效果术前测定针刺镇痛效果合谷穴内注射局麻药procaine阻断针刺镇痛针刺合谷穴针刺穴位注射局麻药加针刺ProcaineinfiltrationintheacupointabolishestheeffectofAA020406080-20020406080100120(n=10)AcupunctureAcupunctureatHekupointPainthresholdchange(%)TimeinminutesProcaineinfiltration+AcupunctureAnalgesiceffectproducedbyperipheralnerveStimulation8DecayoftheEffectofAcupunctureAnalgesiaAftertheterminationofacupuncturestimulationHalflife(T1/2)=16minPainthreshold,%changeTime:20min/unit1010020304050608090709Rabbitexperiment:crossinfusionofCSFEvidenceshowinganeurochemicalbasisforAATFL,%changeTime,minAA+CSFperfusion200100150aCSFDonerrabbitLatventricleIIIventricleperfusate02040600204060InfusionofCSFAcupunctureControl50010Recipientrabbit•从“是什么”What?针刺真的镇痛吗?是的!•到“为什么”Why?针刺为什么会镇痛?机制研究从何入手?•从神经生理(电生理)入手?•从神经化学(物质基础)入手?-神经冲动是电活动-到突触末端是化学活动针刺镇痛的神经化学机制•小分子神经递质5-羟色胺(5-HT),去甲肾上腺素(NA),乙酰胆碱(ACh),etc•神经肽鸦片肽,非鸦片肽Tailflicklatency,%changeTheroleofCNS5-HTinEAanalgesiaICVinjITHinjBrainandspinalcord5-HTmediateEAanalgesia5-HTP5-HTPCinanCinan受体拮抗剂前体物质对照ICVinjITHinjTheroleofCNSNAinEAanalgesiaTheroleofCNSNAinEAanalgesiaTailflicklatency,%changeICVinjITHinjPhentolPhentolDOPSDOPSBrainNAantagonizesEAASpinalNAmediatesEAADOPS前体物质Phentol受体阻断中枢神经递质在脑的不同部位发挥不同作用递质脑脊髓5-HT加强加强NA对抗加强阿片肽年份阿片受体电针Hzμδκ51975+++2Β内啡肽311976+++2强啡肽171979++100孤啡肽171995100内吗啡肽41997++2脑能产生自己的“吗啡”内源性阿片肽氨基酸脑啡肽2HzEAincreasesEnkrelease100HzEAincreasesDynrelease120.000.501.001.502.002.50beforeAfterEAResponder0.000.100.200.30beforeAfterEAResponder0.000.100.200.30Non-responder0.000.501.001.502.002.502Hz100HzEA15HzControlEnkephalin-irinspinalperfusateDynorphin-irinspinalperfusate******2Hz100HzEA15HzControl05001000150020001015050500100015002000051015***2HzEnk100HzDynfmol/mlCSFFrequencydependenceofpeptidereleaseHumanStudyMek-Arg-PheDynorphinAMEK-Arg-PheDynorphinAAstudyincollaborationwithDr.LarsTerenius1315大鼠脊髓中脑啡肽和强啡肽的作用:低频:脑啡肽高频:强啡肽Analgesiceffectofelectro-acupuncturen=13–14rats100500248163264128FrequencyofEA(Hz)脑啡肽抗体阻断低频电针镇痛强啡肽抗体阻断高频电针镇痛电针镇痛效应电针频率Hz脊髓鞘内注射正常兔血清电针不同频率发挥不同作用电针频率(Hz)在CNS释放的神经肽发挥镇痛作用部位低频(2-4)脑啡肽内啡肽脑和脊髓高频(80-120)强啡肽脊髓放电频率Response/Release神经递质神经肽ThomasHokfelt,1991,Neuron7:867-8794低频刺激释放神经递质高频释放神经肽1997ENKANTIBODYNALOXONE197619751979OpioidReceptorsEAacceleratesthereleaseofendogenousopioidsSynergisticInteractionbetweenneuropeptidesPeptidereleasedinCNSEnkDynEnk+DynAB2Hz2Hz100Hz100Hz30691215S2Hz100Hz19TheoptimalcycleofDDwaveTheoptimalcycleseemstobe6second(3low,3high)1mA2mA3mATrendsinNeuroscience,2003;26:17-22电针方法是否有改进余地?穴位接受什么刺激?•机悈刺激:机悈压迫(砭),针刺•温度刺激:温针(经针),灸(经皮)•电刺激:经针(电针),经皮(TENS)电刺激穴位:两种方式•经针(电针,EA)0.5-3.0mA•经皮(经皮电刺激,TENS)5-15mA15电针vianeedlesTENSviaskinelectrodes必须应用恒流(constantcurrent)电刺激仪EqualpotencyoftheanalgesiceffectsproducedbyEAandTENSinratsEATENSEATENS2Hz15Hz100HzPlaceboTFL,%change16CrosstolerancebetweenEAandTENSEATENSN=10-142Hz15Hz100HzTFL,%change电针和TENS的比较刺激方式电流到达深部组织途径刺激范围操作条件EA经过针精确必须针灸医师操作TENS经过皮肤电极覆盖面较大可在医师指导下自行操作相同点:镇痛效果相似,镇痛机制相同,TENS使用方便。HANSforthetreatmentofautism自闭症、孤独症TheHANSunitandtheskinelectrodesAnautismpatientistreatinghimselfwithaHANSunit.18ShenZhenHospital电针镇痛的神经通路•经典神经生物学方法•脑影像方法必须与针刺治疗效果相关者才有意义NervepathwaysforlowandhighfrequencyEAanalgesia100Hz2Hz-endEnkDynPBNArcuateN.Hypoth.PAGMedullaDHNNervepathwaysforlowandhighfrequencyEAanalgesia100Hz2Hz-endEnkDynPBNArcuateN.Hypoth.PAGMedullaDHN27RatexperimentBrainimagingandfunctionalcorrelates•Acupuncturemayactivatemanybrainareas.Butwhichisrelatedwiththegivenfunctionalchange?•ItisadvisabletofindthecorrelationbetweentheBOLDsignalsandthetherapeuticeffectsproducedbyacupuncture28沈阳沈大妇科医院://mobile.sdfk024.com/byby/gjxby/://mobile.sdfk024.com/byby/myxby/沈阳沈大妇科医院://mobile.sdfk024.com/byby/slgby/沈阳沈大妇科医院://mobile.sdfk024.com/byby/zgxby/沈阳沈大妇科医院://mobile.sdfk024.com/fkyz/bdyc/沈阳沈大妇科医院://mobile.sdfk024.com/fkyz/ndy/沈阳沈大妇科医院://mobile.sdfk024.com/fkyz/wybb/沈阳沈大妇科医院://mobile.sdfk024.com/fkyz/zgnmy/://mobile.sdfk024.com/