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曲马朵与二氢埃托啡协同镇痛并推迟大鼠急性耐受

明晓云, 王巍, 韩济生, 罗非

北京大学神经科学研究所，北京大学基础医学院神经生物学系.北京 100083；泰安医学院生理教研室.山东，泰安 271000

摘要

该文旨在研究曲马朵(tramadol, TRA)和二氢埃托啡(dihydroetorphine, DHE)联合用药是否可产生协同镇痛并延缓耐受的发生。TRA (mg，腹腔注射)与DHE (ng，皮下注射)按固定比率给药(1∶6.25, 1∶12.5, 1∶25, 1∶50, 1∶100, 1∶200)，用热辐射甩尾法评价镇痛效应，采用等高线法评估药物的协同作用。在急性耐受实验中，连续 6次注射TRA (20 mg/kg)、DHE (1 000 ng/kg)或两药的组合(TRA 20 mg/kg + DHE 250 ng/kg)。结果显示：(1) 除1 mg∶6.25 ng和1 mg∶50 ng两个比例外，其他所有比例用药均产生显著的协同镇痛效应； (2) TRA与DHE联合用药的疗效在连续给药中持续时间明显延长，提示二者联合使用可延缓耐受。以上结果提示：TRA与DHE在一定剂量比范围内可产生协同镇痛效应，并可推迟耐受的形成。

关键词： 曲马朵; 二氢埃托啡; 协同作用; 镇痛; 急性耐受

Tramadol and dihydroetorphine produce synergistic analgesic effect and postpones acute opiate tolerance in rats

Ming Xiaoyun, Wang Wei, Han Jisheng, Luo Fei

Neuroscience Research Institute and Department of Neurobiology, School of Basic Medicine, Peking University.Beijing 100083；China

Abstract

The present study investigated whether a co-application of tramadol (TRA) and dihydroetorphine (DHE) would exert a synergy in analgesic effect and delay acute tolerance development. Intraperitoneal injection of TRA (in mg) and subcutaneous injection of DHE (in ng) were delivered in fixed proportions (1:6.25, 1:12.5, 1:25, 1:50, 1:100, and 1:200). The effect of analgesia was accessed by tail-flick test and analyzed with isobolographic analysis. For test of acute tolerance, six successive injections of either TRA (20 mg/kg) alone, DHE (1 000 ng/kg) alone, or a combination of TRA (20 mg/kg) and DHE (250 ng/kg) were administered. We found that (1) except for 1 mg: 6.25 ng and 1 mg: 50 ng, combinations, all the other ratios produced a significant synergy in their analgesic effect; (2) the effect of analgesia induced by repeated TRA plus DHE injections lasted significantly longer, indicating a slower onset of acute tolerance. These results indicate that TRA and DHE injections in certain dose ratios can induce synergistic analgesia, which is resistant against the development of acute tolerance.

Key words: Tramadol;Dihydroetorphine;Synergistic effect;Analgesia;Acute tolerance

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引用本文：

明晓云, 王巍, 韩济生, 罗非. 曲马朵与二氢埃托啡协同镇痛并推迟大鼠急性耐受 [J]. 生理学报 2005; 57 (6): .

Ming Xiaoyun, Wang Wei, Han Jisheng, Luo Fei. Tramadol and dihydroetorphine produce synergistic analgesic effect and postpones acute opiate tolerance in rats. Acta Physiol Sin 2005; 57 (6): (in Chinese with English abstract).