Role of TRPV1 and TRPA1 in visceral hypersensitivity to colorectal distension during experimental colitis in rats

• Published in: European journal of pharmacology Vol. 698; no. 1-3; pp. 404 - 412
• Main Authors: Vermeulen, Wim, Joris G., De Man, Heiko U., De Schepper, Bult, Hidde, Moreels, Tom G., Pelckmans, Paul A., Benedicte Y., De Winter
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05.01.2013
• Subjects: Acetanilides - administration & dosage; Acetanilides - pharmacology; Animals; Antagonists; Colitis; Colitis - metabolism; Colitis - physiopathology; Colon - drug effects; Colon - metabolism; Colon - physiopathology; Drug Synergism; endoscopy; ethanol; Female; histology; hypersensitivity; microscopy; myeloperoxidase; Pain; pharmacology; Purines - administration & dosage; Purines - pharmacology; Pyrazines - administration & dosage; Pyrazines - pharmacology; Pyridines - administration & dosage; Pyridines - pharmacology; Rats; Rats, Wistar; Rectum - drug effects; Rectum - metabolism; Rectum - physiopathology; Reflex - drug effects; spinal cord; sulfonic acid; synergism; Transient receptor potential ankyrin 1; Transient receptor potential vanilloid 1; Trinitrobenzenesulfonic Acid - administration & dosage; Trinitrobenzenesulfonic Acid - pharmacology; TRPA1 Cation Channel; TRPC Cation Channels - antagonists & inhibitors; TRPC Cation Channels - metabolism; TRPV Cation Channels - antagonists & inhibitors; TRPV Cation Channels - metabolism; Visceral hypersensitivity; Transient receptor potential vanilloid 1; Pain; Colitis; Visceral hypersensitivity; Transient receptor potential ankyrin 1
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2012.10.014

The aim of the present study is to investigate the effects of TRPV1 and TRPA1 receptor antagonists and their synergism on the visceromotor responses during experimental colitis in rats. Colitis was induced in rats by a TNBS/ethanol enema at day 0 and was assessed at day 3 using endoscopy, histology and a myeloperoxidase assay. The visceromotor response to colorectal distension (10–80mmHg) was evaluated in conscious rats before (control condition) and 3 days after 2,4,6-trinitrobenzene sulfonic acid (TNBS) administration (colitis condition). At day 3, visceromotor responses were assessed before and after treatment with a TRPV1 (BCTC) or TRPA1 (TCS-5861528) receptor antagonist either alone or in combination and either after intraperitoneal or intrathecal administration. Endoscopy, microscopy and myeloperoxidase activity indicated severe colonic tissue damage 3 days after TNBS administration. Colorectal distension-evoked visceromotor responses demonstrated a 2.9-fold increase during acute colitis (day 3) compared to control conditions. Intraperitoneal and intrathecal administration of BCTC or TCS-5861528 partially reversed the colitis-induced increase in visceromotor responses compared to control conditions (P<0.05). Intraperitoneal blockade of TRPA1 plus TRPV1 further decreased the enhanced visceromotor responses at high distension pressures (40–80mmHg) compared to blockade of either TRPV1 or TRPA1 alone. This synergistic effect was not seen after combined intrathecal blockade of TRPA1 plus TRPV1. The present study demonstrates that in the rat, TRPV1 and TRPA1 play a pivotal role in visceral hypersensitivity at the peripheral and spinal cord level during acute TNBS colitis. Target interaction, however, is presumably mediated via a peripheral site of action.