孤啡肽基因敲除小鼠电针镇痛作用增强

POTENTIATION OF ELECTROACUPUNCTURE ANALGESIA IN ORPHNIN FQ KNOCKOUT MICE~#

目的 :孤啡肽是阿片受体样受体 (ORL1)的内源性配基 ,它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 (SP 36)与三阴交 (SP 6) ,电针参数采用韩氏仪恒流方波输出 ,强度 1.0 1.2 1.4mA ,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基因敲除小鼠基础痛阈明显延长 ,对 10 0Hz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 10 0Hz针刺镇痛有拮抗作用。

Aim: Exogenously administered orphanin FQ (OFQ) has been reported to antagonize morphine analgesia and electroacupuncture (EA) analgesia (EAA) in the brain but potentiate morphine analgesia and EAA in the spinal cord of rats. Here we report the effectiveness of EAA in OFQ knockout mice. Methods: Two pairs of metallic acupuncture needles were inserted into specific acupoints ST 36 and SP 6, the needles were connected to one of the output channels of an electric pulse generator named HANS. EA parameters were as follows: constant current output, rectangular (square) pulses, intensities increased with stepwise fashion at 1.0 1.2 1.4 mA, 10 min for each step, frequencies were 100 Hz (0.2 ms pulse) or 2 Hz (0.6 ms pulse). The pain threshold was measured by radiant heat-induced tail flick latency (TFL). Three TFL values taken before EA stimulation were averaged as basal TFL. Wild type and knockout animals were divided randomly into 3 groups: needle control, 100 Hz EA and 2 Hz EA. The peak value obtained among the 6 time points (3 tests during and 3 tests after EA stimulation) was taken to represent the EA effect. The net change of this peak value relative to its own basal TFL (T peak T basal ) was calculated, and analyzed by Analysis of Variance (ANOVA) among groups. Results: The basal threshold in knockout mice was significantly longer than that in the wild type animals. The analgesic effect induced by EA at 100 Hz, but not 2 Hz, was significantly stronger in OFQ knockout mice. Conclusion: Endogenous OFQ seems to increase the sensitivity of nociception and plays an antagonistic role in 100 Hz electroacupuncture-induced analgesia.