delta-opioid receptors and nitric oxide mediate the analgesic effect of Crotalus durissus terrificus snake venom.
The antinociceptive effect of Crotalus durissus terrificus venom was investigated in a model of inflammatory hyperalgesia induced by carrageenin. The rat paw pressure test was applied before and 3 h after the intraplantar (i.pl.) injection of carrageenin. The venom administered per os before and 1 or 2 h after carrageenin blocked hyperalgesia. When carrageenin was injected in both hind paws and naloxone into one hind paw, antinociception was abolished only in the paw injected with naloxone. D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr amide (CTOP) and nor-binaltorphimine, antagonists of micro- and kappa-opioid receptors, respectively, did not alter the effect of the venom. N,N-diallyl-Tyr-Aib-Aib-Phe-Leu (ICI 174,864), an antagonist of delta-opioid receptors, antagonised this effect. Prolonged administration of the venom did not induce tolerance to this antinociceptive effect. N(G)-methyl-L-arginine (L-NMMA) and methylene blue, inhibitors of nitric oxide synthase and soluble guanylate cyclase, respectively, injected i.pl., antagonised antinociception. These data indicate that both delta-opioid receptors and nitric oxide participate in the mediation of the peripheral antinociceptive effect of C. durissus terrificus venom.
Picolo
G
G
Laboratory of Pathophysiology, Butantan Institute, Av. Vital Brazil, 1500, 05503-900, São Paulo, Brazil.
Giorgi
R
R
Cury
Y
Y
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000378:metabolism; D002351:Carrageenan; D003435:Crotalid Venoms / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009292:Narcotic Antagonists / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors; D019323:omega-N-Methylarginine / Q000494:pharmacology
D018712:Analgesics, Non-Narcotic; D003435:Crotalid Venoms; D004791:Enzyme Inhibitors; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D002351:Carrageenan; D001120:Arginine; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D008751:Methylene Blue