Page 18 - 麻醉与监护论坛2015年第11期

刘双庆1 侯 炯2 摘要

1.解放军总医院第一附属医院重症医学科，北京 100037； 目的：本研究中，我们检验了对大鼠重复皮下注射瑞芬太尼是否可以引
2.第二军医大学长海医院麻醉科，上海 200433 起镇痛耐受。方法：将20只雄性S D大鼠随机分为低剂量组（L组）、中剂量组
（M组）、高剂量组（H组）和生理盐水对照组（S组），每组5只。在60m i n的
时间内，分别将3种不同剂量（3u g/k g、6u g/k g和12u g/k g）的瑞芬太尼及生理
盐水进行皮下注射，每次注射时间间隔为10m i n。通过大鼠对热刺激的甩尾时
间（TF，tail flick）来衡量瑞芬太尼的镇痛效应。结果：我们发现接受瑞芬
太尼的大鼠与安慰剂组大鼠相比甩尾时间明显延长。然而，3个剂量组的镇痛
效应均出现降低，低、中、高剂量组的耐药度分别为47%、55%和73%。结论：
对大鼠重复皮下注射瑞芬太尼可以造成急性镇痛耐受，耐受程度与药物剂量相
关。本实验动物模型也许对于研究阿片类制剂（例如瑞芬太尼）急性耐受的分
子机制来说是一个有力工具。

关键词：瑞芬太尼；急性耐受；镇痛

通过对大鼠皮下注射瑞芬太尼可以导致剂

量依赖性镇痛耐受

Dose-dependent Analgesic Tolerance Evoked by Subcutaneous
Injection of Remifentanil in Rats

S. Q. Liu1, J. Hou2

1.Department of SICU, First Affiliated Hospital of General Hospital of PLA, Beijing 100037, China;
2.Department of Anesthesiology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China

Abstract

Objective. In this study we examined whether acute analgesic tolerance to remifentanil could be induced by
repeatedly subcutaneous injection in rat.

Methods. A total of twenty male SD rats were divided into four groups, the 3ug/kg group(group L), the 6ug/
kg group(group M), the 12ug/kg group(group H) and the saline group(group S) randomly. Three different dosages of
remifentanil, i.e. 3ug/kg (low); 6ug/kg (medium),12ug/kg (high) were injected subcutaneously with time interval of
10 min for a total period of 60 min. The physiological saline was injected in the saline group. The analgesic effects of
remifentanil were determined by tail flick (TF) latency to heat stimuli.

Results. We found that rats received remifentanil exhibited significantly prolonged TF time in three concentrations
in comparison to placebo control. But the analgesic effects by remifentanil declined in all three concentrations and the
degrees of tolerance were 47%, 55% and 73% for low, medium and high dosages, respectively.

Conclusion. The present results indicate that repeatedly subcutaneous remifentanil injection lead to the development
of acute analgesic tolerance in rats, and the extent of tolerance is associated with the dosage applied. However, the most
pronounced analgesic effect was found in the medium concentration (6ug/kg). The flick tail time was already prolonged
to the same extent as high concentration (12 µg/kg) at 20 min point and most importantly, persisted significantly
throughout the experimental time points, indicating a slow development of opoid tolerance after remifentanil
adminstration.This model therefore may provide a useful experimental tool to study molecular mechanism underlying
acute analgesic tolerance to opioids such as remifentanil.

Key Words. remifentanil; acute tolerance; analgesia

Laboratory and Clinical Investigation 65 FAM 2015 Jan/Feb Vol.22 Issue 1
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