Anti-exudative effects of opioid receptor agonists in a rat model of carrageenan-induced acute inflammation of the paw

Abstract

We evaluated the anti-exudative effects (Evan's blue) of mu-, delta- and kappa-opioid receptor agonists in a rat model of carrageenan-induced acute inflammation. The contribution of different components was assessed after the administration of: cyclosporine A, capsaicin, 6-hydroxydopamine, compound 48/80, and specific histamine-receptor antagonists. The results show that the mu-opioid receptor agonists morphine and fentanyl and the delta-opioid receptor agonists DPDPE (enkephalin, [ d-Pen 2,5]) and SNC 80 ((+)-4-[(α R)-α((2 S,5 R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]- N, N diethylbenzamide) decrease plasma extravasation in a dose-dependent manner, with a biphasic response. The effects were reversed by specific antagonists, and are predominantly mediated by peripheral opioid receptors. The integrity of sensory and sympathetic fibres is essential for the anti-exudative effects of fentanyl and DPDPE. Histamine and functional histamine H 2 and H 3 receptors are required for morphine and fentanyl (but not DPDPE) inhibition of plasma extravasation, suggesting different mechanism for mu- and delta-opioid receptor agonists. The present findings implicate multiple sites and mechanisms in the anti-exudative effects of exogenous opioids.