Colitis generates remote antinociception in rats: the role of the l-arginine/NO/cGMP/PKG/KATP pathway and involvement of cannabinoid and opioid systems
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Objective and design
The aim of this study was to investigate the possible involvement of the NO/cGMP/PKG/K ATP + pathway, cannabinoids and opioids in remote antinociception associated with 2,4,6-trinitrobenzene sulph onic acid (TNBS)-induced colitis.
TNBS-induced colitis was induced by intracolonic administration of 20 mg of TNBS in 50 % ethanol. After induction, carrageenan (500 μg/paw) or prostaglandin (PG) E2 (100 ng/paw) was injected in the rat’s plantar surface and hypersensitivity was evaluated by the electronic von Frey test. Rats were pre-treated with l-Noarg one hour before carrageenan injection. l-Arginine was given 10 min before l-Noarg injections. ODQ, KT 5823, glibenclamide (Glib), naloxone and AM 251 or AM 630 were administered 30 min prior to carrageenan or PGE2 treatments.
Colitis induction by TNBS reduced PGE2 or carrageenan-induced hypersensitivity. Antinociception produced by TNBS-induced colitis was reversed significantly (P < 0.05) by l-Noarg, ODQ, KT 5823, glibenclamide, naloxone, AM251 and AM630 treatments.
TNBS-induced colitis causes antinociception in the rat paw. This disorder appears to be mediated by activation of the NO/cGMP/PKG/KATP pathway, endocannabinoids and endogenous opioids. This information may contribute to a better understanding of peripheral neurological dysfunctions occurring in Crohn’s disease.
KeywordsTNBS-induced colitis Hypersensitivity NO Opioids Cannabinoids
The authors gratefully acknowledge the technical assistance of Maria Silvandira Freire França, and we thank UFPI/CNPq for fellowship support.
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