The peripheral L-arginine-nitric oxide-cyclic GMP pathway and ATP-sensitive K⺠channels are involved in the antinociceptive effect of crotalphine on neuropathic pain in rats.
Behav Pharmacol
; 23(1): 14-24, 2012 Feb.
Article
en En
| MEDLINE
| ID: mdl-22126967
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⺠channels. Crotalphine (0.2 or 5 µg/kg, orally; 0.0006 µg/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 δ-opioid receptors, and partially reversed by norbinaltorphimine, an antagonist of κ-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⺠channel blocker. The results suggest that peripheral δ-opioid and κ-opioid receptors, the nitric oxide-cyclic GMP pathway, and ATP-sensitive K⺠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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Péptidos
/
Arginina
/
GMP Cíclico
/
Canales KATP
/
Analgésicos
/
Neuralgia
/
Óxido Nítrico
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
Idioma:
En
Revista:
Behav Pharmacol
Asunto de la revista:
CIENCIAS DO COMPORTAMENTO
/
FARMACOLOGIA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Brasil
Pais de publicación:
Reino Unido