title: Colitis generates remote antinociception in rats: the role of the L-arginine/NO/cGMP/PKG/KATP pathway and involvement of cannabinoid and opioid systems.
abstract: OBJECTIVE
  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.
authors.affiliation: LAFFEX Laboratory of Experimental Physiopharmacology, School of Physiotherapy, Biotechnology and Biodiversity Center Research (BIOTEC), Federal University of Piauí-CMRV, Parnaíba, PI, 64202-020, Brazil, andreluiz@ufpi.edu.br.
authors.forename: André Luiz
authors.initials: AL
authors.lastname: dos Reis Barbosa
authors.forename: Rhamon Barroso
authors.initials: RB
authors.lastname: de Sousa
authors.forename: João Nathanael Lima
authors.initials: JN
authors.lastname: Torres
authors.forename: Thiago Mattar
authors.initials: TM
authors.lastname: Cunha
authors.forename: Fernando
authors.initials: F
authors.lastname: de Queiroz Cunha
authors.forename: Pedro Marcos Gomes
authors.initials: PM
authors.lastname: Soares
authors.forename: Ronaldo
authors.initials: R
authors.lastname: de Albuquerque Ribeiro
authors.forename: Mariana Lima
authors.initials: ML
authors.lastname: Vale
authors.forename: Marcellus Henrique Loiola Ponte
authors.initials: MH
authors.lastname: Souza
mesh_terms: D000701:Analgesics, Opioid / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000737:chemistry; D002186:Cannabinoids / Q000378:metabolism; D002351:Carrageenan / Q000737:chemistry; D003092:Colitis / Q000378:metabolism*; D003106:Colon / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D015232:Dinoprostone / Q000737:chemistry; D054086:KATP Channels / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism*; D059225:Nociception / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014302:Trinitrobenzenesulfonic Acid / Q000737:chemistry
chemical_list: D000701:Analgesics, Opioid; D002186:Cannabinoids; D054086:KATP Channels; D009569:Nitric Oxide; D014302:Trinitrobenzenesulfonic Acid; D002351:Carrageenan; D001120:Arginine; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP; D015232:Dinoprostone