Hong Y, Abbott F V
Department of Psychiatry, McGill University, Montreal, Canada.
Eur J Pharmacol. 1995 Apr 13;277(1):21-8. doi: 10.1016/0014-2999(95)00045-m.
The effects of local treatment with opioid receptor agonists on the early (0-10 min) and late (20-40 min) behavioural response and extravasation induced by intraplantar injection of 1% formalin in rats were examined. The mu-opioid receptor agonist [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO) depressed pain behaviour in the late phase, and extravasation in both phases. The kappa-opioid receptor agonist trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl] benzeneacetamide methanesulfonate (U50,488H) suppressed the behavioural response in both phases, but extravasation was enhanced in the early phase and not altered in the late phase. The delta-opioid receptor agonist [D-Pen2,5]enkephalin (DPDPE) enhanced the behavioural response in the late phase, but inhibited extravasation in the both early and late phases. Systemic injection of the agonists had no effects, and pretreatment with s.c. naloxone methiodide reversed the effects of locally administered agonists. These data (1) support the notion that different pathophysiological mechanisms underlie the two phases of the formalin test, and (2) indicate that depending on the receptor specificity, opioid receptor agonists have both pro- and antinociceptive effects, as well as pro- and antiinflammatory activity.
研究了阿片受体激动剂局部给药对大鼠足底注射1%福尔马林诱导的早期（0 - 10分钟）和晚期（20 - 40分钟）行为反应及血管外渗的影响。μ-阿片受体激动剂[D - Ala2，N - Me - Phe4，Gly5 - ol]脑啡肽（DAMGO）可抑制晚期疼痛行为以及两个阶段的血管外渗。κ-阿片受体激动剂反式-(±)-3,4 - 二氯 - N - 甲基 - N - (2 - [1 - 吡咯烷基]苯乙酰胺甲磺酸盐（U50,488H）在两个阶段均抑制行为反应，但早期血管外渗增强，晚期无变化。δ-阿片受体激动剂[D - Pen2,5]脑啡肽（DPDPE）增强晚期行为反应，但在早期和晚期均抑制血管外渗。激动剂全身注射无作用，皮下注射甲硫氨酸纳洛酮预处理可逆转局部给药激动剂的作用。这些数据（1）支持福尔马林试验两个阶段存在不同病理生理机制的观点，（2）表明根据受体特异性，阿片受体激动剂具有促痛和抗痛作用以及促炎和抗炎活性。
