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 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.

cGMP and cGMP-Dependent Protein Kinase I Pathway in Dorsal Root Ganglia Contributes to Bone Cancer Pain in Rats

“…Local administration of L-arginine (NO donor) or other drugs that could activate NO could induce antinociceptive effect by activating K ATP channel in DRG neurons. [27][28][29] However, in this study, we observed that cGMP-cGKI pathway in DRG contributes to bone cancer pain by promoting the hyperexcitability of DRG neurons. These different consequences may result from that different targets of cGMP-cGKI pathway were activated by different drug administration pattern.…”

Effects of chlorogenic acid on voltage-gated potassium channels of trigeminal ganglion neurons in an inflammatory environment

“…In peripheral inflammation such as TMJ inflammation, PGE 2 sensitize peripheral nociceptors through activation of EP receptors on peripheral nerve terminals (Kumazawa et al, 1993;Barbosa et al, 2012), which cause an increase in the excitability of peripheral neurons (Rodrigues et al, 2006;Omote et al, 2002).…”