The peripheral L-arginine-nitric oxide-cyclic GMP pathway and ATP-sensitive K+ channels are involved in the antinociceptive effect of crotalphine on neuropathic pain in rats

Autor(es)

Gutierrez, Vanessa P. ^[1] ; Zambelli, Vanessa O. ^[1] ; Picolo, Gisele ^[1] ; Chacur, Marucia ^[2] ; Sampaio, Sandra C. ^[3] ; Brigatte, Patricia ^[1] ; Konno, Katsuhiro ^[4] ; Cury, Yara ^{[1, 3]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Special Lab Pain & Signaling, Butantan Inst, BR-05503900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, BR-05503900 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Pathophysiol Lab, Butantan Inst, BR-05503900 Sao Paulo - Brazil

^[4] Toyama Univ, Inst Nat Med, Toyama 930 - Japan

• Tipo de documento: Artigo Científico
• Fonte: Behavioural Pharmacology; v. 23, n. 1, p. 14-24, 2012.
• Citações Web of Science: 18

Resumo

Crotalphine, a 14 amino acid peptide first isolated from the venom of the South American rattlesnake Crotalus durissus terrificus, induces a peripheral long-lasting and opioid receptor-mediated antinociceptive effect in a rat model of neuropathic pain induced by chronic constriction of the sciatic nerve. In the present study, we further characterized the molecular mechanisms involved in this effect, determining the type of opioid receptor responsible for this effect and the involvement of the nitric oxide-cyclic GMP pathway and of K+ channels. Crotalphine (0.2 or 5 mu g/kg, orally; 0.0006 mu g/paw), administered on day 14 after nerve constriction, inhibited mechanical hyperalgesia and low-threshold mechanical allodynia. The effect of the peptide was antagonized by intraplantar administration of naltrindole, an antagonist of delta-opioid receptors, and partially reversed by norbinaltorphimine, an antagonist of kappa-opioid receptors. The effect of crotalphine was also blocked by 7-nitroindazole, an inhibitor of the neuronal nitric oxide synthase; by 1H-(1,2,4) oxadiazolo[4,3-a]quinoxaline-1-one, an inhibitor of guanylate cyclase activation; and by glibenclamide, an ATP-sensitive K+ channel blocker. The results suggest that peripheral delta-opioid and kappa-opioid receptors, the nitric oxide-cyclic GMP pathway, and ATP-sensitive K+ channels are involved in the antinociceptive effect of crotalphine. The present data point to the therapeutic potential of this peptide for the treatment of chronic neuropathic pain. Behavioural Pharmacology 23:14-24 (C) 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins. (AU)

• Processo FAPESP: 07/02478-4 - Avaliação da possível diferença na sensibilidade dolorosa de ratos machos e fêmeas e da resposta de cada sexo ao CNF 021.03, um analgésico tipo opióide
• Beneficiário: Yara Cury
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• Modalidade de apoio: Bolsas no Brasil - Mestrado
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