激活GABA_B受体在针刺镇痛中的作用

目的 :脑室注射γ 氨基丁酸 (GABA)A受体的拮抗剂荷包牡丹碱 (Bic)未能阻断针刺镇痛效应 ,微电泳导入Bic部分阻断电针抑制脊髓背角伤害性反应 ,说明GABA可通过激活A受体参与针刺镇痛中脊髓节段性抑制。本文进一步探讨了激活GABAB 受体在针刺镇痛中的作用。方法 :以辐射热照射大鼠尾部引起甩尾反射潜伏期作为痛阈的指标 ,以针刺“次”穴后痛阈最大变化百分率判断镇痛效应 ,观察脑室注射 (icv) 5μL或蛛网膜下腔 (ith)注射 1 0 μLGABAB 受体的拮抗剂CGP 55845对针刺镇痛效应的影响。每组 6～ 8例。结果 :icvGABA( 1 2 5μg、2 50 μg、50 0 μg)或GABAB 受体激动剂苯氯丁氨酸 (Baclofen ,2 5ng、2 50ng、2 50 0ng)可产生剂量依赖的镇痛效应。icvCGP 55845( 5ng、50ng)可大部分阻断GABA和Baclofen的镇痛效应。针刺双侧“次”穴( 50Hz,1～ 2mA) 1 0min ,痛阈提高到针前值的 ( 1 42 .5± 2 .1 ) % ,镇痛效应显著。针前icvCGP55845针后痛阈分别提高到 ( 1 1 1 .2± 1 .2 ) %和 ( 1 1 2 .1± 1 .1 ) % ,阻断率分别为 73 .7%和 71 .6% ,和事先icv生理盐水 ( 1 43 .7± 2 .0 ) %相比 ,阻断效应明显。若针刺前ithCGP 55845( 50ng、50 0ng) ,也能明显阻断针刺镇痛效应。结论 :脑内注射GABA或Baclofen可通过激?

The Important Role of Activation of GABAB Receptors in Acupuncture Analgesia

Objective: In this paper, the effects of intra-cerebroventricular and intrathecal injection (icv and ith) of CGP 55845, a potent and selective antagonist against GABA B receptor, on acupuncture analgesia were investigated. Methods: Female Wistar rats were used in the present study. Before experiments, under 10% urethane (1 g/kg, i.p.) anesthesia, a stainless steel cannula was implanted into the left lateral ventricle (B:-1.0～1.2,L:1.5～2.0,H:3.0) according to the "Rat Brain's Sterotaxic Atlas" and fixed with zinc phosphate cement for i.c.v injection. Similarly, a PE-10 polyethylene duct (external diameter 0.61 mm) was inserted into the spinal subarachnoid space till the lumbar enlargement in line with Yaksh and Rudy's method . Radiation heat stimulation was applied to the rat tail and the pain threshold (PT) was detected by tail flick latency tests. Bilateral "Ciliao" (BL 32) were punctured and stimulated electrically with WQ-10 Electroacupuncture Anesthesia Apparatus (50 Hz, 1～2 mA, continuous waves and duration of 10 min). There are 6～8 rats in each group. Results: ① After icv GABA ( 125, 250, 500 μg/5 μL) or baclofen (Bac), an agonist of GABA B receptor at dose of 0.025, 0.25. 2.5 μg/5 μL, the pain threshold (PT) values were increased significantly, presenting a dose-dependent effect, which was markedly blocked by pretreatment of icv CGP 55845 (5, 50 ng). It indicates that icv GABA and baclofen could produce analgesic effects mediated by activation of GABA B receptors. ② After electroacupuncture (EA) at bilateral "Ciliao" (BL 32), PT were raised to (142.5±2.1) % and (143.7±2.0)% without and with pretreatment of normal saline. When pretreated with icv CGP 55845 at dose of 5 and 50 ng /5 μL, acupuncture analgesic effects were significantly blocked by 73.7% and 71.6% ; PT raised to (111.2±1.2)% and (112.1±1.1)%. It indicates that GABA in brain may be involved in acupuncture analgesia mediated mainly by activation of GABA B receptors. ③ When pretreated with ith saline and after EA of bilatreral "Ciliao"(BL 32), PT were raised to (138.2±1.6)%. When pretreated with ith CGP 55845 at dose of 50 and 500 ng /10 μL, PT were raised to (119.0±1.0)% and (109.1±1.9)% respectively, indicating reduce of acupuncture analgesia by 52.6% and 76.7%. It means that at the spinal level, GABA may also be involved in acupuncture analgesia. Conclusion: Microinjection of GABA or Baclofen in the brain may generate dose-dependant analgesic effect via activation of GABA B receptor, and GABA B receptors in the brain and GABA A (our past results) and B receptors in the spinal cord are involved in acupuncture anesthesia.