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

ULTRA-LOW DOSE OF NALOXONE POTENTIATES ANALGESIC EFFECT INDUCED BY ELECTROACUPUNCTURE, BUT DOES NOT AFFECT ITS SUPPRESSIVE EFFECT ON MORPHINE WITHDRAWAL IN RATS

摘要:

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。

Abstract:

Aim: Naloxone ( NX) is a well-known opioid receptor antagonist that blocks opioid analgesia. However there was an unexpected and paradoxical observation that administration of extremely low doses of NX enhanced, rather than attenuated, the analgesic effects produced by small doses of morphine or other opioid agonists. The aim of this study was to determine whether ultra-low dose of NX could increase the efficacy of EA-induced analgesia and the suppression of morphine withdrawal in rats. Methods: (1 ) adult male Sprague Dawley ( SD) rats were randomly divided into seven groups of 8 -10 each, receiving normal saline (NS) , NX 10 ng/kg, 2 Hz EA, 100 Hz EA, 2 Hz or 100 Hz EA plus NX 10 ng/kg, or no treatment as blank control. Nociceptive threshold was measured by radiant heat-induced tail flick latency (TFL). (2) Adult male SD rats were made dependent on morphine by multiple injections of increasing doses of morphine for 5 days. The rats were randomly divided into six groups of 8 - 10 each, receiving NS, NX 10 ng/kg, 2 Hz EA, 100 Hz EA, and 2 Hz or 100 Hz EA plus NX 10 ng/kg, respectively. They were given EA for 30 min 6 h after the last injection of morphine, followed by intraperitoneal (i. p. ) administration of naloxone (1 mg/kg). Body weight loss (g) was measured before and 60 min after the NX injection. Results: (1) NX 10 ng/kg did not significantly influence the basal level of TFL, but significantly potentiate the analgesic effect induced by 2 Hz EA, with the effect lasting as long as 120 min. The analgesic effect produced by 100 Hz EA was not affected. (2) NX 10 ng/kg did not significantly influence NX-induced body weight loss in morphine-dependent rat. 2 Hz or 100 Hz EA for 30 min significantly reduced the body weight loss (P <0. 01). The efficacy of EA was not affected by NX 10 ng/ kg. Conclusion: (1 ) Ultra-low dose of NX selectively increases the analgesic effect induced by 2 Hz EA in the rat, which may have potential clinical impact. (2) It did not affect the efficacy of EA in suppressing body weight loss in morphine withdrawal rats.