大鼠脊髓5－羟色胺1A受体和1C／2受体亚型参与高频电针镇痛

通过脊髓蛛网膜下腔慢性埋植导管分别注射５－ＨＴ受体的多种拮抗剂，分析了大鼠脊髓５－ＨＴ受体的三个主要类型５－ＨＴ１、５－ＨＴ２和５－ＨＴ３受体在高频电针镇痛中的作用。实验结果表明：ｉ．ｔ．注射５－ＨＴ１Ａ受体拮抗剂ｓｐｉｐｅｒｏｎｅ２５μｇ不影响１００Ｈｚ电针的平均针效（Ｐ＞０．０５），但可阻断电针后效应（Ｐ＜０．０１）；ｉ．ｔ．注射５－ＨＴ１ｃ／２受体拮抗剂ｍｉａｎｓｅｒｉｎ５０μｇ可阻断１００Ｈｚ电针的平均针效，也可阻断电针后效应（Ｐ＜０．０１）；ｉ．ｔ．注射５－ＨＴ２受体拮抗剂１－ＮＰ２０μｇ和５－ＨＴ３受体拮抗剂ＩＣＳ２０５－９３０１００μｇ对１００Ｈｚ电针镇痛没有显著影响（Ｐ＞０．０５）。提示大鼠脊髓５－ＨＴ１Ａ受体和５－ＨＴ１ｃ／２受体参与介导１００Ｈｚ电针镇痛，而５－ＨＴ３受体可能不起主要作用。     

ACTH及电针对甲醛痛敏大鼠脊髓NOS阳性神经元增多的影响

本文采用ＮＡＤＰＨ－ｄ组化染色技术,研究鞘内注射（ｉ．ｔ．）ＡＣＴＨ及电针刺激（ＥＡ）对甲醛痛敏大鼠脊髓背角浅层ＮＯＳ阳性神经元增多的影响。结果显示ＡＣＴＨ（０．５Ｕ,ｉ．ｔ．）及电针（１ｍＡ５０Ｈｚ,５ｍＡ５Ｈｚ,１ｍＡ５Ｈｚ）刺激“夹脊穴”３０ｍｉｎ均可显著抑制脊髓背角浅层ＮＯＳ阳性神经元增多;ｉ．ｔ．ＡＣＴＨ（０．５Ｕ）和电针刺激（１ｍＡ５Ｈｚ）同时给予时,抑制作用显著增加;ｉ．ｔ．ＮＯ前体     

大鼠脊髓5—羟色胺1A受体和1C／2受体亚型参与高频电针镇痛

通过脊髓蛛网膜下腔慢性埋植导管分别注射５－ＨＴ受体的多种拮抗剂，分析了大鼠脊髓５－ＨＴ受体的三个主要类型５－ＨＴ１、５－ＨＴ２和５－ＨＴ３受体在高频电针镇痛中的作用。实验结果表明：ｉ．ｔ．注射５－ＨＴ１Ａ受体拮抗剂ｓｐｉｐｅｒｏｎｅ ２５μｇ不影响１００ＨＺ电针的平均针数（Ｐ〉０．０５），但可阻断电针后效应（Ｐ〈０．０１）；ｉ．ｔ．注射５－ＨＴ１Ｃ／２受体拮抗剂ｍｉａｎｓｅｒｉｎ５０μｇ可阻断１０     

中枢去甲肾上腺素和强啡肽A（1—17）在痛觉调制中的相互作用

大鼠以辐射热甩尾法测痛。应用脊髓蛛网膜下腔（ｉ．ｔ．）连续累加注射法观察药物的镇痛作用。（１）ｉ．ｔ．单独注射强啡肽Ａ（１－１７）２．５μｇ本身无镇痛作用，但与去甲肾上腺素（ＮＥ）合用时却能产生协同镇痛作用；该作用即能被ｉ．ｔ．注射α受体拮抗剂酚妥拉明３０μｇ所对抗，也能被κ阿片受体拮抗剂Ｎｏｒ－ＢＮＩＯ９μｇ所对抗。（２）强啡肽Ａ和ＮＥ的协同镇痛揭示在两种受体激动剂协同作用时，阻断其中一种受体，     

变频体表电刺激促使慢性痛患者脊髓中释放强啡肽

本工作将皮肤电极置于人体穴位表面，用不同频率的方波脉冲进行电刺激，观察脑脊液中甲啡肽（ＭＥＫ）代谢片段ＭＥＫ１－４和ＭＥＫ２－４以及强啡肽Ａ（Ｄｙｎ－Ａ）含量的变化。观察结果如下：（１）急性和慢性疼痛患者脑脊液中ＭＥＫ１－４含量与正常组相比均无明显变化，但急性痛患者脑脊液中ＭＥＫ２－４及Ｄｙｎ－Ａ的含量显著低于正常人；（２）对照刺激或２／１５Ｈｚ变频刺激对患者脑脊液中上述神经肽片段的含量无明显影响，但２／１００Ｈｚ变频刺激后，慢性痛患者脑脊液中Ｄｙｎ－Ａ含量显著增加。韩济生实验室的动物实验结果表明，高、低频电针刺激可分别使大鼠脊髓释放Ｄｙｎ－Ａ和ＭＥＫ，并参与电针镇痛过程。本工作在疼痛患者身上也观察到不同频率的电刺激确可引起不同种类阿片肽的释放。这一发现可能有助于解释特定参数的电刺激对特定癌症的治疗作用。     

曲马多对大鼠低频电针镇痛的加强作用

以大鼠为研究对象，采用辐射热甩尾测痛的方法，观察了曲马多（Ｔｒａｍａｄｏｌ，ＴＲＡ）对不同频率电针镇痛效果的影响。结果表明：腹腔（ｉ．ｐ．）注射不同剂量的ＴＲＡ可剂量依赖地提高大鼠的甩尾阈，与对照组相比，６．２５、１２．５、２５和５０ｍｇ／ｋｇ剂量的ＴＲＡ有明显的镇痛效应（ＡＮＯＶＡ，Ｐ〈０．０１）。腹腔注射阈下剂量９３．１２５ｍｇ／ｋｇ）的ＴＲＡ可显著地提高２Ｈｚ和１５Ｈｚ电针镇痛效果，但对１０     

中枢去甲肾上腺素与E－2078和盐酸二氢埃托啡在痛觉调制中的相互作用

给大鼠脊髓蛛网膜下腔（ｉ．ｔ．）单独注射去甲肾上腺素（ＮＥ）２．μｇ或强啡肽Ａ（１～８）衍生物（Ｋ激动剂）Ｅ－２０７８８０ｎｇ可产生轻度但显著的镇痛效应。同时ｉ．ｔ．注射１／２量ＮＥ和１／２量Ｅ－２０７８所产生的镇痛效应显著高于单独ＮＥ或Ｅ－２０７８的效应。将Ｅ－２０７８的剂量增加到９６和１１５ｎｇ（依次递增２０％），也得到与上述类似的结果，提示Ｅ－２０７８与ＮＥ在脊髓产生协同镇痛作用。用同样的方法观察皮下注射（ｓ．ｃ．）μ激动剂盐酸二氢埃托啡（ＤＨＥ）对ｉ．ｔ．注射ＮＥ镇痛的影响，发现ｓ．ｃ．ＤＨＥ在２６８，３７５，５２５ｎｇ三个剂量水平（依次递增４０％）下，１／２量ＮＥ和１／２量ＤＨＥ联合注药组产生的镇痛效应与单纯ＮＥ或ＤＨＥ组相比均无显著性差异。以上结果提示，脊髓内的ＮＥ与。阿片激动剂Ｅ－２０７８有协同镇痛作用，而与μ阿片激动剂ＤＨＥ仅有加和作用。     

中枢去甲肾上腺素与E—2078和盐本二氢埃托啡在痛觉调制中？…

给大鼠脊髓蛛网膜下腔（ｉ．ｔ．）单独注射去肾上腺素（ＮＥ）２．５μｇ或强啡肽Ａ（１￣８）衍生物（κ激素剂）Ｅ－２０７８８０ｎｇ可产生轻度但显著的镇痛效应。同时ｉ．ｔ．注射１／２量ＮＥ和１／２量Ｅ－２０７８所产生的镇痛效应显著高于单独ＮＥ或Ｅ－２０７８的效应。将Ｅ－２０８７的剂量增加到９６和１１５ｎｇ（依次递产２０％），也得到与上述类似的结果，提示Ｅ－２０７８与ＮＥ在脊髓产生协同镇痛作用。用同样的方     

100Hz电针促进吗啡依赖和戒断大鼠脊髓强啡肽的释放

目的：研究在吗啡依赖和戒断大鼠１００ＨＺ电针是否仍有镇痛作用。该作用是否仍由脊髓强啡肽通过ｋ受体介导。方法：测定辐射热甩尾阈（ＴＦＬ）作为痛阈。结果：（１）给大鼠皮下注射递增量吗啡８天造成大鼠对吗啡的依赖。这时给以１００ＨＺ电针，ＴＦＬ仍有显著升高，此作用可被大剂量纳洛酮翻转，提示由ｋ阿片受体介导；（２）吗啡依赖和或断大鼠脊髓灌注液中强腓肽放免活性明显降低，１００ＨＺ电针使之显著回升。结论：在大鼠     

CCK—B受体拮抗剂L—365,260翻转100Hz慢性电针耐受

４８只高针效大鼠随机分为６组，每组大鼠（８只）每天给予１００Ｈｚ电针一次（３０ｍｉｎ），连续６天。其电针镇痛效果逐渐降低。形成慢性电针耐受。在第７天，６组大鼠分别皮下（ｓ．ｃ．）注射配药液或不同剂量的ＣＣＫ－Ｂ受体拮抗剂Ｌ－３６５，２６０（０．０３￣３ｍｇ／ｋｇ）．ｓ．ｃ．注射配药液的对照大鼠仍然表现出明显的电针耐受现象，而ｓ．ｃ注射Ｌ－３６５，２６０（０．１ｍｇ，０．３ｍｇ／ｋｇ）则可汉有效地翻     

极小剂量纳洛酮增强电针的镇痛作用但不影响电针对吗啡戒断症状的抑制作用

目的:纳洛酮(naloxone,NX)是一种阿片受体拮抗剂,应用于大鼠,在1～10mg/kg范围内能对抗吗啡镇痛和电针(electroacupuncture,EA)镇痛。但有人报道,极小剂量NX可加强吗啡镇痛。本工作观察极小剂量NX是否能加强大鼠电针镇痛,及电针对大鼠吗啡戒断的抑制作用。方法:选用成年雄性SD大鼠,分两批进行实验。第一批以辐射热甩尾阈(TFL)作为大鼠痛阈指标,检测腹腔注射(i.p.)NX10ng/kg对2Hz EA和100Hz EA镇痛效应的影响。第二批在慢性吗啡依赖大鼠模型上,以体重丢失作为吗啡戒断反应指标,观察i.p NX 10 ng/kg对 2Hz EA和 100Hz EA抑制 NX(lmg/kg,i.p.)诱发的体重丢失的影响。结果:(1)EA之前10分钟 i.p. NX 10 ng/kg,不仅能显著增强2Hz EA的镇痛作用(P<0.05),而且可使其镇痛效应延长至120分钟;同样剂量NX对100 Hz EA的镇痛效应无明显影响(P>0.05)。(2)EA之前10分钟i.p. NX 10 ng/kg,对两种频率EA抑制吗啡戒断大鼠体重丢失的效应均无显著影响。结论:极小剂量的NX能增强和延长2Hz EA的镇痛作用,该发现可能具有临床应用意义。极小剂量的NX未能影响EA抑制吗啡戒断大鼠体重丢失的作用,这可能与吗啡戒断状态下阿片受体的功能改变有关。     

The integrity of the anterior pretectal nucleus and dorsolateral funiculus is necessary for electroacupuncture‐induced analgesia in the rat tail‐flick test

Previous studies have indicated that the anterior pretectal nucleus (APtN) is implicated in pathways that descend through the dorsolateral funiculus (DLF) to modulate nociceptive inputs in the spinal dorsal horn. The activation of descending inhibitory mechanisms also seems to be involved in electroacupuncture (EA)‐induced analgesia. This study utilized the tail‐flick test to examine the changes produced by DLF lesion or injection of 2% lidocaine into the APtN in the analgesia induced by 2 or 100 Hz EA applied to the Zusanli (ST36) and Sanyinjiao (SP6) acupoints in lightly anesthetized rats. Tail‐flick latency was significantly increased by EA, the effect of 2 Hz EA lasting longer than that produced by 100 Hz EA. The effect of either 2 or 100 Hz EA did not occur in DLF lesion rats. The effect of 2 Hz EA did not occur in rats with neural block of the whole or dorsal APtN. In contrast, the effect of 100 Hz EA was reduced in rats with neural block of the whole APtN, but remained unchanged in rats with neural block of the dorsal APtN. We thus conclude that the integrity of the APtN and DLF is necessary for EA‐induced analgesia in the rat tail‐flick test. In addition, the integrity of the dorsal APtN is necessary for the analgesic effect of 2 but not 100 Hz EA.     

Dynorphin: important mediator for electroacupuncture analgesia in the spinal cord of the rabbit

Intrathecal injection of 12 nmol of dynorphin elicited marked analgesia as measured by tail flick latency, the effect being about 20 times more potent than with morphine. This analgesic effect could be reversed by naloxone at a dose 1.5-fold higher than that needed to reverse morphine analgesia. Intrathecal injection of anti-dynorphin antibody blocked electroacupuncture (EA) analgesia by 77%, the effect lasting for at least 4 h. In rabbits made tolerant to EA analgesia by long-term EA stimulation, intrathecal injection of dynorphin no longer exhibited an analgesic effect. No analgesia was noticed when dynorphin (10 nmol) was injected into the periaqueductal grey (PAG) of the rabbit, nor was EA analgesia blocked by anti-dynorphin antibody injected into PAG. These results suggest that dynorphin reduces nocifensive responses in the spinal cord and may play an important role in mediating EA analgesia at the spinal level.     

大鼠电针镇痛的个体差异性及其与基础痛阈的关系

电针镇痛具有个体差异性。我们采用聚类分析的统计学方法,以１００Ｈｚ电针３０分钟内辐射热甩尾潜伏期升高百分数之平均值为指标,将１６８例大鼠分为优针效和劣地效两个群体,其针效至少在两之内保持相对稳定。电针镇痛效果与基础痛阈呈显著正相关。即优针效鼠的基础痛阈显著高于劣针效鼠。     

孤啡肽基因敲除小鼠电针镇痛作用增强

目的：孤啡肽是阿片受体样受体（ORL1）的内源性配基,蛇能调节疼痛与镇痛反应以及针刺镇痛反应,但各个实验室所得结果各不相同。本文利用OFQ基因敲除的小鼠为工具,观察内源性OFQ在针刺镇痛中的作用。方法：采用本实验室建立的小鼠电针方法,选用穴位足三里（SP36）与三阴交（SP6）,电针参数采用韩氏仪恒流方波输出,强度1.0-1.2-1.4 mA,每10min递增一级。痛阈的改变以热辐射甩尾来评价。结果：与野生型小鼠相比,OFQ基因高除小鼠基础痛阈明显延长,对100Hz电针镇痛反应显著增强,但不影响2Hz电针镇痛。结论：在整体情况下,内源性OFQ有紧张性的致痛敏作用,并对100Hz针刺镇痛有拮抗作用。     

小剂量MK—801加强100Hz电针抑制大鼠吗啡戒断症状的作用

目的 :观察小剂量MK 80 1(dizocilpine)是否能加强 10 0Hz电针 (electroacupuncture ,EA)抑制大鼠吗啡戒断症状的作用。方法 :大鼠皮下注射递增剂量的吗啡 5天 (每天 3次 ) ,使其对吗啡形成依赖 ,最后一次注射吗啡后 1h ,分别腹腔 (i.p .,0 .0 3mg/kg)或蛛网膜下腔 (i.t.,10 0ng/ 10 μl)注射MK 80 1,注射后 15min给予 10 0HzEA。MK 80 1注射和 10 0HzEA共进行 3次 ,两次之间相隔5h。最后一次EA结束后 30mini.p .纳洛酮 (1mg/kg)催促戒断症状 ,并观察记录 5种戒断症状的表现。结果 :(1)单纯i.p .MK 80 1仅能显著降低直立症状 ;单纯 10 0HzEA能够显著降低直立和振翼样抖动 ;i.p .MK 80 1联合 10 0HzEA能显著降低跳跃、直立、振翼样抖动和体重丢失等 4种戒断症状。 (2 )单纯i.t.MK 80 1能显著降低振翼样抖动 ;i.t .MK 80 1联合EA能显著降低上述四种戒断症状。结论 :小剂量的MK 80 1可加强 10 0HzEA抑制戒断症状的作用 ;联合使用的效果优于单纯应用EA或MK 80 1。     

电针抑制iGluRs激动剂鞘内给药易化的大鼠脊髓背角突触传递LTP

目的:观察电针对离子型谷氨酸受体(iGluRs)激动剂易化脊髓背角神经元而形成的长时程增强(LTP)的抑制作用,并探讨其机制.方法:大鼠脊髓L4/L5节段细胞外记录脊髓背角C-纤维诱发场电位的LTP.iGluRs激动剂NMDA或[±]-AMPA HBr 40pg鞘内给药(i.t.)易化脊髓背角神经元;对照组i.t.生理盐水2μl.2 Hz,1 mA电针(EA)环跳和委中穴.观察电针对iGluRs激动剂i.t.易化的LTP的抑制作用.结果:对照组低强度强直刺激(HFS)前、后脊髓背角LTP)的变化率无统计学差异;i.t.NMDA或[±]-AMPA HBr后低强度HFS,可引起显著的LTP,与对照组比较P相似文献   

中脑导水管周围灰质内催产素对痛阈和电针镇痛效应的影响

本工作以钾离子透入法引起大鼠甩尾反应的电流强度（ｍＡ）为痛反应指标，观察了中脑导水管周围灰质（ＰＡＧ）腹外侧区注射催产素（ＯＴ）和抗催产素血清（ＡＯＴＳ）对大鼠痛阈和电针镇痛效应的影响。结果表明，ＰＡＧ注射ＯＴ能增加大鼠痛阈和电针镇痛效应；注射ＡＯＴＳ以中和内源性的ＯＴ后，对大鼠痛阈虽克明显影响，但能显著降低电针期的停针后的电针镇痛效应。提示ＰＡＧ内生理水平的ＯＴ在电针镇痛中发挥一定作用。     

小鼠低频和高频电针镇痛阿片机制的探讨

探讨小鼠低频和高频电针镇痛的阿片机制。方法：采用交叉耐受和受体药理学方法,以甩尾潜伏期增加的百发数作为评判电针镇痛效果的指标。结果：（１）吗啡镇痛与２Ｈｚ电针镇痛之间存在交叉耐受。（２）２／１００Ｈｚ电针镇痛分别与２Ｈｚ、１００Ｈｚ电针镇痛存在交叉耐受;而２Ｈｚ电针镇痛与１００Ｈｚ电针镇痛不存在交叉耐受。（３）ＣＣＫ受体拮抗剂Ｌ３６５,２６０可显著加强１００Ｈｚ电针镇痛效应,对２Ｈｚ电针镇痛无明显     

Intracerebroventricular physostigmine-induced analgesia: enhancement by naloxone, beta-funaltrexamine and nor-binaltorphimine and antagonism by dynorphin A (1-17)

The antinociceptive action (tail-flick test) of physostigmine given i.c.v. to mice was enhanced by the administration intrathecally (i.t.) of narcotic antagonists. Doses, i.t., as low as 0.1 fentog of naloxone, 0.25 ng of beta-funaltrexamine and 0.1 ng of nor-binaltorphimine enhanced physostigmine, 2 micrograms i.c.v., analgesia. These doses of opioid antagonists did not inhibit spinal mu receptors or kappa receptor agonist-induced analgesia as assessed by absence of effect on Tyr-D-Ala2-N-MePhe4-Gly-ol5 or U50,488H i.t. analgesia. Enhancing effects of the opioid antagonists were interpreted to indicate that i.c.v. physostigmine-induced analgesia was mediated spinally by an endogenous opioid which had an antagonistic effect. This putative opioid antagonist was postulated to be dynorphin A (1-17). Thus, i.t. administration of small doses of less than 10 pg of dynorphin was shown to antagonize the analgesic action of physostigmine, i.c.v. Furthermore, this effect of dynorphin was attenuated by the doses of naloxone, beta-funaltrexamine or nor-binaltorphimine which were effective in enhancing physostigmine-induced analgesia. We concluded that physostigmine given i.c.v. had two actions, the first produced analgesia and the second activated a system which had an antianalgesic effect. Evidence indicated that the latter effect was mediated by dynorphin A (1-17). This concept of dynorphin action may be the basis for some of the unusual findings of the analgesic action of naloxone in other situations and support the concept for a descending dynorphin A (1-17)-mediated antianalgesic system.