Anti-exudative effects of opioid receptor agonists in a rat model of carrageenan-induced acute inflammation of the paw.
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-[(alpha R)-alpha((2S,5R)-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.
Romero
Asunción
A
Department of Pharmacology, Bellvitge Biomedical Research Institute, University of Barcelona, Spain.
Planas
Eulalia
E
Poveda
Raquel
R
Sánchez
Silvia
S
Pol
Olga
O
Puig
Margarita M
MM
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D002351:Carrageenan; D016572:Cyclosporine / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000517:prevention & control; D005283:Fentanyl / Q000494:pharmacology; D006614:Hindlimb / Q000187:drug effects* / Q000473:pathology; D006633:Histamine Antagonists / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009292:Narcotic Antagonists; D016627:Oxidopamine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000819:agonists*; D017465:Receptors, Opioid, delta / Q000819:agonists; D017473:Receptors, Opioid, kappa / Q000819:agonists; D017450:Receptors, Opioid, mu / Q000819:agonists; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D001549:Benzamides; D006633:Histamine Antagonists; D009292:Narcotic Antagonists; D010879:Piperazines; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C088464:4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide; D003189:p-Methoxy-N-methylphenethylamine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D016572:Cyclosporine; D020881:Enkephalin, D-Penicillamine (2,5)-; D016627:Oxidopamine; D002351:Carrageenan; D002211:Capsaicin; D005283:Fentanyl