大鼠福尔马林试验中阿片类药物耐受性的发展

The development of opioid tolerance in the formalin test in the rat.

作者信息

Detweiler Dawn J, Rohde Dana S, Basbaum Allan I

机构信息

Department of Anesthesiology, University of California at San Francisco, San Francisco, CA 94143, USA Department of Anatomy, University of California at San Francisco, San Francisco, CA 94143, USA Department of Physiology, University of California at San Francisco, San Francisco, CA 94143, USA W.M. Keck Foundation Center for Integrative Neuroscience, University of California at San Francisco, San Francisco, CA 94143, USA.

出版信息

Pain. 1995 Nov;63(2):251-254. doi: 10.1016/0304-3959(95)00051-S.

DOI:10.1016/0304-3959(95)00051-S

PMID:8628591

Abstract

The formalin test produces persistent pain in animals and is believed to provide a better model of the pain experienced by humans than do tests that measure reflex nociceptive thresholds. The present study evaluated whether tolerance to morphine develops in the formalin test in the rat. Morphine (75 mg) or vehicle pellets were implanted subcutaneously for 5 consecutive days. On the 6th day, a subcutaneous (s.c.) dose of either morphine (10 mg/kg) or saline was given 30 min prior to the injection of 50 microliters of 5% formalin into the left hindpaw of the rats. In vehicle-pelleted rats administered saline, formalin evoked characteristic pain behavior consisting of licking, biting and flinching of the affected hindpaw. The pain behavior in morphine-tolerant rats given morphine did not differ significantly from the saline control; i.e., tolerance to the analgesic effect of morphine was demonstrable in the formalin test. These results do not agree with previous published reports. Rather, these results suggest that the mechanisms involved in morphine analgesia in the formalin test and in reflex nociceptive tests are similar and subject to the same problem of tolerance with chronic opioid administration.

摘要

福尔马林试验可使动物产生持续性疼痛，并且人们认为该试验比那些测量反射性伤害感受阈值的试验能更好地模拟人类所经历的疼痛。本研究评估了大鼠在福尔马林试验中是否会对吗啡产生耐受性。连续5天皮下植入吗啡（75毫克）或赋形剂药丸。在第6天，于向大鼠左后爪注射50微升5%福尔马林前30分钟，皮下注射吗啡（10毫克/千克）或生理盐水。在接受生理盐水的赋形剂药丸植入大鼠中，福尔马林引发了特征性疼痛行为，包括受影响后爪的舔舐、啃咬和退缩。给予吗啡的吗啡耐受大鼠的疼痛行为与生理盐水对照组相比无显著差异；也就是说，在福尔马林试验中可证明对吗啡的镇痛作用产生了耐受性。这些结果与先前发表的报告不一致。相反，这些结果表明，福尔马林试验和反射性伤害感受试验中吗啡镇痛所涉及的机制相似，并且在长期给予阿片类药物时会出现相同的耐受性问题。