Levine J D, Taiwo Y O
Department of Medicine, University of California, San Francisco 94143-0724.
Neuroscience. 1989;32(3):571-5. doi: 10.1016/0306-4522(89)90279-0.
The intradermal injection of mu (morphine, Tyr-D-Ala-Gly-NMe-Phe-Gly-ol and morphiceptin), kappa (trans-3,4-dichloro-N-methyl-N[2-(1-pyrrolidinyl) cyclohexyl]benzeneactemide) and delta ([D-Pen2.5]-enkephalin and [D-Ser2]-[Leu]enkephalin-Thr) selective opioid-agonists, by themselves, did not significantly affect the mechanical nociceptive threshold in the hindpaw of the rat. Intradermal injection of mu, but not delta or kappa opioid-agonists, however, produced dose-dependent inhibition of prostaglandin E2-induced hyperalgesia. The analgesic effect of the mu-agonist morphine was dose-dependently antagonized by naloxone and prevented by co-injection of pertussis toxin. Morphine did not, however, alter the hyperalgesia induced by 8-bromo cyclic adenosine monophosphate. We conclude that the analgesic action of opioids on the peripheral terminals of primary afferents is via a binding site with characteristics of the mu-opioid receptor and that this action is mediated by inhibition of the cyclic adenosine monophosphate second messenger system.
皮内注射μ型（吗啡、酪氨酰-D-丙氨酰-甘氨酰-N-甲基苯丙氨酰-甘氨醇和吗啡受体激动肽）、κ型（反式-3,4-二氯-N-甲基-N-[2-(1-吡咯烷基)环己基]苯乙酰胺）和δ型（[D-青霉胺2,5]-脑啡肽和[D-丝氨酸2]-[亮氨酸]脑啡肽-苏氨酸）选择性阿片样物质激动剂本身，对大鼠后爪的机械性伤害感受阈值没有显著影响。然而，皮内注射μ型阿片样物质激动剂，而非δ型或κ型阿片样物质激动剂，可产生剂量依赖性地抑制前列腺素E2诱导的痛觉过敏。μ型激动剂吗啡的镇痛作用呈剂量依赖性地被纳洛酮拮抗，并被百日咳毒素共注射所阻断。然而，吗啡并未改变8-溴环磷酸腺苷诱导的痛觉过敏。我们得出结论，阿片样物质对初级传入神经外周终末的镇痛作用是通过具有μ型阿片受体特征的结合位点实现的，并且该作用是由对环磷酸腺苷第二信使系统的抑制介导的。
