Participation of the NO/cGMP/K+ATP pathway in the antinociception induced by Walker tumor bearing in rats

Brazilian Journal of Medical and Biological Research

A.l.r. Barbosa¹  C.a. Pinheiro¹  G.j. Oliveira¹  J.n.l. Torres¹  M.o. Moraes¹  R.a. Ribeiro¹  M.l. Vale¹  M.h.l.p. Souza¹ 

[1],Universidade Federal do Ceará Faculdade de Medicina Departamento de Fisiologia e FarmacologiaFortaleza CE ,Brasil

关键词: Walker 246 tumor-bearing rats;    Hypernociception;    Nitric oxide;    Carrageenan;   

DOI  :  10.1590/S0100-879X2012007500047

来源: SciELO

【 摘 要 】

Implantation of Walker 256 tumor decreases acute systemic inflammation in rats. Inflammatory hyperalgesia is one of the most important events of acute inflammation. The L-arginine/NO/cGMP/K+ATP pathway has been proposed as the mechanism of peripheral antinociception mediated by several drugs and physical exercise. The objective of this study was to investigate a possible involvement of the NO/cGMP/K+ATP pathway in antinociception induced in Walker 256 tumor-bearing male Wistar rats (180-220 g). The groups consisted of 5-6 animals. Mechanical inflammatory hypernociception was evaluated using an electronic version of the von Frey test. Walker tumor (4th and 7th day post-implantation) reduced prostaglandin E2- (PGE2, 400 ng/paw; 50 µL; intraplantar injection) and carrageenan-induced hypernociception (500 µg/paw; 100 µL; intraplantar injection). Walker tumor-induced analgesia was reversed (99.3% for carrageenan and 77.2% for PGE2) by a selective inhibitor of nitric oxide synthase (L-NAME; 90 mg/kg, ip) and L-arginine (200 mg/kg, ip), which prevented (80% for carrageenan and 65% for PGE2) the effect of L-NAME. Treatment with the soluble guanylyl cyclase inhibitor ODQ (100% for carrageenan and 95% for PGE2; 8 µg/paw) and the ATP-sensitive K+ channel (KATP) blocker glibenclamide (87.5% for carrageenan and 100% for PGE2; 160 µg/paw) reversed the antinociceptive effect of tumor bearing in a statistically significant manner (P < 0.05). The present study confirmed an intrinsic peripheral antinociceptive effect of Walker tumor bearing in rats. This antinociceptive effect seemed to be mediated by activation of the NO/cGMP pathway followed by the opening of KATP channels.

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