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β-内啡肽基因敲除小鼠2Hz电针镇痛效果显著降低

DECREASE OF LOW FREQUENCY (2Hz) ELECTROACUPUNCTURE ANALGESIA IN MICE LACKING β ENDORPHIN

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【作者】 万有JS.Mogil黄诚韩济生

【Author】 WAN You 1,2 , Jeffrey S. Mogil 2, HUANG Cheng 1, HAN Ji Sheng 1 1 Neuroscience Research Institute, Beijing Medical University, 38 Xueyuan Road, Beijing 100083, P.R. China. 2 Department of Psychology and Neuroscience Program, University of Illinois at Urbana Champaign, 603 E. Daniel St, Champaign, IL 61820, USA.

【机构】 北京医科大学神经科学研究所!北京100083DepartmentofPsychologyandNeuroscienceProgramUniversityofIllinoisatUrbanaChampaign!603E.DanielStChampaignIL61820USA

【摘要】 针刺镇痛的机理研究发现,不同频率的电针刺激释放中枢内不同的阿片肽,即2 Hz 低频电针主要释放β内啡肽,而100 Hz 高频电针主要释放强啡肽。本实验试图在缺乏β内啡肽( P O M C 基因敲除) 的小鼠上进一步验证这一理论。实验在缺乏β内啡肽的小鼠和相应的野生型小鼠上进行,以热辐射甩尾潜伏期测定痛阈,选定足三里和三阴交穴位,以韩氏穴位神经刺激仪( H A N S) 的恒流、方波输出进行电针刺激。实验发现:(1) 与相应野生型小鼠相比,缺乏β内啡肽的小鼠2 Hz 低强度电针(0 .3 ~0 .4 ~0 .5 m A) 镇痛作用明显减弱;(2) 100 Hz 低强度电针(0 .8 ~1 .0 ~1 .2 m A) 镇痛,两种小鼠无显著差别;(3) 2 Hz 高强度电针(0 .8 ~1 .0 ~1 .2 m A) 不论在野生型小鼠还是缺乏β内啡肽小鼠均有镇痛作用。上述实验结果表明,2 Hz 低强度电针镇痛主要由β内啡肽介导,进一步验证了不同频率电针具有不同神经化学机理的学说。

【Abstract】 It has been established that the mechanisms underlying the analgesic effect induced by electroacupuncture (EA) of low frequency (2~4 Hz) and high frequency (100~200 Hz) are not only quantitatively different but also qualitatively distinct. It has been shown that 2 Hz EA accelerates the release of β endorphin and met enkephalin in CNS, whereas high frequency EA (100 Hz in rats) accelerates the release of Supported by NIDA/INVEST grant (You Wan), National Institute on Drug Abuse, NIH, USA and NIDA grant DA03983 (Jisheng Han), NIH, USA dynorphin in the spinal cord. In the present experiment, we tested this hypothesis in mice lacking beta endorphin. Two pairs of metallic needles were inserted into the acupoints ST 36 and SP6, the needles were fixed in situ and then connected to an electric pulse generator HANS. Electroacupuncture (EA) parameters were as follows: constant current output, rectangular (square) wave pulses with 0.6 ms pulse width in 2 Hz, and 0.2 ms in 100 Hz. Tail flick latency (TFL) evoked by radiant heat was used to serve as the endpoint of pain threshold. The results were as follows: (1) EA of 2 Hz with low intensities (0.3~0.4~0.5 mA in each 10 min steps) showed significantly lower analgesic effect in mice lacking beta endorphin compared to that in wild type mice, whereas 100 Hz low intensity EA stimulation produced analgesia in both β endorphin knock out (KO) mice and wild type mice. (2) EA of 2 Hz at higher intensities (0.8~1.0~1.2 mA) which produced stress reactions induced analgesic effects in knock out as well as in wild type mice. These findings indicated that (1) β endorphin plays an important role in mediating low frequency (2 Hz) EA analgesia, (2) β endorphin is not necessary for mediating high frequency (100 Hz) EA analgesia or stress induced analgesia. These results provide genetic support for the hypothesis that the analgesic effect induced by EA of different frequencies is mediated by different kinds of opioid peptides.

【基金】 美国国立健康研究院药物滥用研究所基金;DA03983基金
  • 【文献出处】 中国疼痛医学杂志 ,Chinese Journal of Pain Medicine , 编辑部邮箱 ,1999年03期
  • 【分类号】R245
  • 【被引频次】17
  • 【下载频次】274
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