Miaskowski C, Taiwo Y O, Levine J D
School of Nursing, University of California, San Francisco 94143.
Eur J Pharmacol. 1991 Dec 3;205(3):247-52. doi: 10.1016/0014-2999(91)90905-6.
This study evaluated the contribution of supraspinal opioid receptors to the production of antinociception, in the rat. I.c.v. administration of a selective mu- (DAMGO) and a selective delta- (DPDPE), but not a selective kappa- (U50,488H) opioid receptor agonist, produced significant dose-dependent increase in mechanical nociceptive thresholds. ICI 174,864, a delta-opioid receptor antagonist, completely blocked the antinociceptive effects produced by DPDPE ([D-Pen2,D-Pen5]enkephalin) at a dose that had no effect on the increases in nociceptive thresholds produced by DAMGO ([D-Ala2,N-MePhe4,Gly5-ol]enkephalin). The simultaneous i.c.v. administration of a low-antinociceptive dose of DAMGO or DPDPE given in combination with sequentially increasing doses of the other opioid agonist, produced synergy (i.e., a more than additive antinociceptive effect), at the lower doses tested. The results of these experiments provide evidence to support the suggestion that both supraspinal mu- and delta-opioid receptors contribute to the production of antinociception, in the rat.
本研究评估了大鼠脊髓上阿片受体在产生抗伤害感受中的作用。脑室内注射选择性μ-（DAMGO）和选择性δ-（DPDPE）阿片受体激动剂，但不包括选择性κ-（U50,488H）阿片受体激动剂，可使机械性伤害感受阈值产生显著的剂量依赖性升高。δ-阿片受体拮抗剂ICI 174,864能完全阻断DPDPE（[D- Pen2，D- Pen5]脑啡肽）产生的抗伤害感受作用，而该剂量对DAMGO（[D- Ala2，N- MePhe4，Gly5-ol]脑啡肽）引起的伤害感受阈值升高没有影响。在较低测试剂量下，同时脑室内注射低抗伤害感受剂量的DAMGO或DPDPE，并依次增加另一种阿片受体激动剂的剂量，会产生协同作用（即超过相加的抗伤害感受效应）。这些实验结果为支持以下观点提供了证据：脊髓上的μ-和δ-阿片受体均参与了大鼠抗伤害感受的产生。
