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

• Main Authors: A.L.R. Barbosa, C.A. Pinheiro, G.J. Oliveira, J.N.L. Torres, M.O. Moraes, R.A. Ribeiro, M.L. Vale, M.H.L.P. Souza
• Format: Article
• Language: English
• Published: Associação Brasileira de Divulgação Científica 2012-06-01
• Series: Brazilian Journal of Medical and Biological Research
• Subjects: Walker 246 tumor-bearing rats; Hypernociception; Nitric oxide; Carrageenan
• Online Access: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2012000600009
• ISSN: 0100-879X; 1414-431X

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.