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(Reference retrieved automatically from Google Scholar through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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]
Total Authors: 8
Affiliation:
[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
Total Affiliations: 4
Document type: Journal article
Source: Behavioural Pharmacology; v. 23, n. 1, p. 14-24, 2012.
Web of Science Citations: 18
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 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)

FAPESP's process: 07/02478-4 - Sex differences in nociception and in the antinociceptive effect of CNF 021.03, an opioid analgesic
Grantee:Yara Cury
Support Opportunities: Regular Research Grants
FAPESP's process: 98/14307-9 - Center for Applied Toxinology
Grantee:Hugo Aguirre Armelin
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 08/57898-0 - National Institute of Science and Technology on Toxins
Grantee:Osvaldo Augusto Brazil Esteves Sant'Anna
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 07/00135-2 - Evaluation of expression and activation of opioid receptors after peripheral injury in rats
Grantee:Vanessa Olzon Zambelli
Support Opportunities: Scholarships in Brazil - Doctorate