title: Participation of the NO/cGMP/K+ATP pathway in the antinociception induced by Walker tumor bearing in rats.
abstract: 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 E(2)- (PGE(2), 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 PGE(2)) 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 PGE(2)) the effect of L-NAME. Treatment with the soluble guanylyl cyclase inhibitor ODQ (100% for carrageenan and 95% for PGE(2); 8 µg/paw) and the ATP-sensitive K(+) channel (KATP) blocker glibenclamide (87.5% for carrageenan and 100% for PGE(2); 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.
authors.affiliation: Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE, Brasil.
authors.forename: A L R
authors.initials: AL
authors.lastname: Barbosa
authors.forename: C A
authors.initials: CA
authors.lastname: Pinheiro
authors.forename: G J
authors.initials: GJ
authors.lastname: Oliveira
authors.forename: J N L
authors.initials: JN
authors.lastname: Torres
authors.forename: M O
authors.initials: MO
authors.lastname: Moraes
authors.forename: R A
authors.initials: RA
authors.lastname: Ribeiro
authors.forename: M L
authors.initials: ML
authors.lastname: Vale
authors.forename: M H L P
authors.initials: MH
authors.lastname: Souza
mesh_terms: D000700:Analgesics / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000378:metabolism; D002279:Carcinoma 256, Walker / Q000378:metabolism*; D002351:Carrageenan / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology; D054086:KATP Channels / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D059225:Nociception / Q000187:drug effects*; D010069:Oxadiazoles / Q000494:pharmacology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects* / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
chemical_list: D000700:Analgesics; D054086:KATP Channels; D010069:Oxadiazoles; D011810:Quinoxalines; D009569:Nitric Oxide; D002351:Carrageenan; D001120:Arginine; D006152:Cyclic GMP; D015232:Dinoprostone