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

Authors :
Gutierrez, Vanessa P.
Zambelli, Vanessa O.
Picolo, Gisele
Chacur, Marucia
Sampaio, Sandra C.
Brigatte, Patricia
Konno, Katsuhiro
Cury, Yara
Source :
Behavioural Pharmacology; February 2012, Vol. 23 Issue: 1 p14-24, 11p
Publication Year :
2012

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 Kchannels. Crotalphine (0.2 or 5 gkg, orally; 0.0006 gpaw), 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 -opioid receptors, and partially reversed by norbinaltorphimine, an antagonist of -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) oxadiazolo4,3-aquinoxaline-1-one, an inhibitor of guanylate cyclase activation; and by glibenclamide, an ATP-sensitive Kchannel blocker. The results suggest that peripheral -opioid and -opioid receptors, the nitric oxide–cyclic GMP pathway, and ATP-sensitive Kchannels 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.

Details

Language :
English
ISSN :
09558810 and 14735849
Volume :
23
Issue :
1
Database :
Supplemental Index
Journal :
Behavioural Pharmacology
Publication Type :
Periodical
Accession number :
ejs48597833
Full Text :
https://doi.org/10.1097/FBP.0b013e32834eafbc