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1、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-induced analgesiaHuman Observation:020406080-20020406080100120*Acupuncture at Heku pointPain threshold ch
2、ange (%)Time in minutesneedlemanipulation(n=66)control group(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Site specificity Meridine/channel (morphological evidence?) Acupoints (precise to mm level?) Body points (Chinese original) or Ear points (French scholars) Bio-ele
3、ctrically sensitive sites, or densely innervated sites relative rather than absolute specificity12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Procaine infiltration in the acupointabolishes the e
4、ffect of AA020406080-20020406080100120(n=10) AcupunctureAcupuncture at Heku pointPain threshold change (%)Time in minutesProcaine infiltration + Acupuncture Analgesic effect produced by peripheral nerve Stimulation8Decay of the Effect of Acupuncture AnalgesiaAfter the termination of acupuncture stim
5、ulationHalf life (T1/2) = 16 minPain threshold, % changeTime: 20 min / unit101002030405060809070Hegu 17.6 NMP 15.0 Zusanli 15.5 HG+ZSL 15.5 9Rabbit experiment: cross infusion of CSFEvidence showing a neurochemical basis for AATFL, % changeTime, minAA + CSF perfusion 200 100 150 aCSFDoner rabbitLat v
6、entricleIII ventricleperfusate 0 2040 60 0 2040 60Infusion of CSFAcupunctureControl50010Recipient rabbit 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Tail flick latency, % c
7、hange The role of CNS 5-HT in EA analgesiaICV injITH injBrain and spinal cord 5-HT mediate EA analgesia5-HTP5-HTPCinanCinan受体拮抗剂前体物质对照ICV injITH inj The role of CNS NA in EA analgesia The role of CNS NA in EA analgesiaTail flick latency, % changeICV injITH injPhentolPhentolDOPSDOPSBrain NA antagoniz
8、es EAASpinal NA mediates EAADOPS 前体物质Phentol受体阻断中枢神经递质在脑的不同部位 发挥不同作用脑能产生自己的脑能产生自己的“ “吗啡吗啡” ”内源性阿片肽内源性阿片肽氨基酸 脑啡肽 2Hz EA increases Enk release 100Hz EA increases Dyn release120.000.501.001.502.002.50beforeAfter EAResponder0.000.100.200.30beforeAfter EAResponder0.000.100.200.30Non-responder0.000.501.00
9、1.502.002.50Non-responder2Hz100HzEA15HzControlEnkephalin-ir in spinal perfusateDynorphin-ir in spinal perfusate *2Hz100HzEA15HzControl05001000150020001015050500100015002000051015*2Hz Enk100Hz Dynfmol / ml CSFFrequency dependence of peptide release Human StudyMek-Arg-PheDynorphin AMEK-Arg-PheDynorphi
10、n AA study in collaboration with Dr. Lars Terenius 1315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Analgesic effect of electro-acupunctureDYN ABMEK ABn = 13 14 rats100500248163264128Frequency of EA (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 发挥不同作用放电频率Response / Release神经递质神经肽Thomas Hokfelt, 1991
11、, Neuron 7:867-8794低频刺激释放神经递质高频释放神经肽2 Hz100 Hz1997EMEM-EPENKDYNANTIBODYNALOXONE197619751979Opioid ReceptorsEA accelerates the release of endogenous opioidsSynergisticSynergistic Interaction between neuropeptidesInteraction between neuropeptidesPeptide released in CNSEnkDynEnk + DynAB2Hz2Hz100Hz100Hz
12、30691215 S2Hz100Hz19 The optimal cycle of DD waveThe optimal cycle seems to be 6 second (3 low, 3 high)1 mA2 mA3 mATrends in Neuroscience, 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 - 3.0 mA 经皮 (经皮电刺激，TENS)5 - 15 mA15电针via n
13、eedlesTENSvia skin electrodes必须应用恒流(constant current)电刺激仪Equal potency of the analgesic effects produced by EA and TENS in ratsEATENSEATENS2 Hz15 Hz100 HzPlaceboTFL, % change16Cross tolerance between EA and TENSEATENSN = 10 - 142 Hz15 Hz100 HzTFL, % change电针和TENS的比较相同点：镇痛效果相似，镇痛机制相同，TENS使用方便。HANS fo
14、r the treatment of autism自闭症、孤独症The HANS unit and the skin electrodesAn autism patient is treating himself with a HANS unit.18ShenZhen Hospital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 Nerve pathways for low and high frequency EA analgesia 100 Hz 2 Hz-endEnkDynPBNArcuate N.Hypoth.PAGMedullaDHNNerve
15、pathways for low and high frequency EA analgesia 100 Hz 2 Hz-endEnkDynPBNArcuate N.Hypoth.PAGMedullaDHN27Rat experimentBrain imaging and functional correlates Acupuncture may activate many brain areas. But which is related with the given functional change? It is advisable to find the correlation bet
16、ween the BOLD signals and the therapeutic effects produced by acupuncture28http:/ 沈阳沈大妇科医院http:/ 沈阳沈大妇科医院http:/ 沈阳沈大妇科医院http:/ 沈阳沈大妇科医院http:/ EA increases Dyn release0.000.100.200.30beforeAfter EAResponder0.000.100.200.30Non-responder2Hz100HzEA15HzControlDynorphin-ir in spinal perfusate *Responders and non-responders in acupuncture analgesia0.000.501.001.502.002.50beforeAfter EAResponder0.000.501.001.502.002.50Non-responderEnkephalin-ir in spinal perfusate*2Hz100HzEA15HzControl 2Hz EA increases
