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.

Abstract

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 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⁺ channel blocker. The results suggest that peripheral δ-opioid and κ-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.

• Authors: Vanessa P Gutierrez, Vanessa O Zambelli, Gisele Picolo, Marucia Chacur, Sandra C Sampaio, Patricia Brigatte, Katsuhiro Konno, Yara Cury
• Journal: Behavioural pharmacology (Behav Pharmacol) Vol. 23 Issue 1 Pg. 14-24 (Feb 2012) ISSN: 1473-5849 [Electronic] England
• PMID: 22126967 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics
• KATP Channels
• Peptides
• Receptors, Opioid, delta
• Receptors, Opioid, kappa
• crotalphine
• Nitric Oxide
• Arginine
• Cyclic GMP

Topics

• Analgesics (pharmacology)
• Animals
• Arginine (physiology)
• Cyclic GMP (physiology)
• KATP Channels (physiology)
• Male
• Neuralgia (drug therapy)
• Nitric Oxide (physiology)
• Peptides (pharmacology)
• Rats
• Rats, Wistar
• Receptors, Opioid, delta (physiology)
• Receptors, Opioid, kappa (physiology)
• Signal Transduction (physiology)