Colitis generates remote antinociception in rats: the role of the L-arginine/NO/cGMP/PKG/KATP pathway and involvement of cannabinoid and opioid systems

Inflamm Res. 2014 Dec;63(12):969-77. doi: 10.1007/s00011-014-0773-x. Epub 2014 Oct 7.

Abstract

Objective and design: The aim of this study was to investigate the possible involvement of the NO/cGMP/PKG/KATP+ pathway, cannabinoids and opioids in remote antinociception associated with 2,4,6-trinitrobenzene sulph onic acid (TNBS)-induced colitis.

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / metabolism
  • Animals
  • Arginine / chemistry
  • Cannabinoids / metabolism
  • Carrageenan / chemistry
  • Colitis / metabolism*
  • Colon / drug effects
  • Cyclic GMP / metabolism*
  • Cyclic GMP-Dependent Protein Kinases / metabolism*
  • Dinoprostone / chemistry
  • KATP Channels / metabolism*
  • Male
  • Neurons / drug effects*
  • Nitric Oxide / metabolism*
  • Nociception / drug effects*
  • Rats
  • Rats, Wistar
  • Trinitrobenzenesulfonic Acid / chemistry

Substances

  • Analgesics, Opioid
  • Cannabinoids
  • KATP Channels
  • Nitric Oxide
  • Trinitrobenzenesulfonic Acid
  • Carrageenan
  • Arginine
  • Cyclic GMP-Dependent Protein Kinases
  • Cyclic GMP
  • Dinoprostone