Peripheral neuronal nitric oxide synthase activity mediates the antinociceptive effect of Crotalus durissus terrificus snake venom, a δ- and κ-opioid receptor agonist

• Published in: Life sciences (1973) 2004-06, Vol.75 (5), p.559-573
• Main Authors: Picolo, Gisele, Cury, Yara
• Format: Article
• Language: English
• Subjects: Analgesia; Analgesics - pharmacology; Animals; cGMP-dependent protein kinase; Crotalid Venoms - pharmacology; Crotalus; Crotalus durissus terrificus; Crotalus durissus terrificus venom; Dinoprostone - pharmacology; Drug Antagonism; Enzyme Inhibitors - pharmacology; Hyperalgesia - chemically induced; Hyperalgesia - prevention & control; Indazoles - pharmacology; L-arginine/NO/cGMP pathway; Male; Neuronal nitric oxide (NO) synthase; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase Type I; Opioid receptors; Oxadiazoles - pharmacology; Quinoxalines - pharmacology; Rats; Rats, Wistar; Receptors, Opioid, delta - agonists; Receptors, Opioid, delta - physiology; Receptors, Opioid, kappa - agonists; Receptors, Opioid, kappa - physiology
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2003.12.024

Previous work has shown that nitric oxide (NO) mediates the antinociceptive effect of Crotalus durissus terrificus venom on carrageenin-induced hyperalgesia. In the present study the role of constitutive neuronal or of inducible form of nitric oxide synthase on venom effect was determined. The rat paw prostaglandin E 2 (PGE 2)-induced mechanical hyperalgesia model was used for nociceptive evaluation. The venom (200 μg/kg) administered per oz immediately before prostaglandin induced antinociception that persisted for 120 h. The characterisation of the antinociceptive effect of the venom in this model of hyperalgesia showed that κ and δ-opioid receptors are involved in this effect. 7-nitroindazole (7-NI), a neuronal nitric oxide synthase (NOS) inhibitor, but not L-N 6-(1-iminoethyl)lysine (L-NIL), an inhibitor of the inducible form of NOS, injected by intraplantar (i.pl.) route, antagonized the antinociceptive effect of the venom. The i.pl. administration of 1H-(1,2,4)oxadiazolo[4,3-a]quinoxaline-1-one (ODQ), a seletive guanylate cyclase inhibitor, blocked antinociception, whereas Rp-cGMP triethylamine, a cGMP-dependent protein kinase inhibitor, partially reversed this effect. These data indicate that peripheral κ- and δ-opioid receptors are involved in the antinociceptive effect of Crotalus durissus terrificus on prostaglandin E 2-induced hyperalgesia. Peripheral nitric oxide, generated by neuronal NO synthase, and cGMP/PKc are responsible, at least partially, for the molecular mechanisms of venom effect.