Proteinase-activated receptor-2 agonist induced visceral hyperalgesia is prevented by dexamethasone via regulation of colonic mast cells in rats

Low-grade inflammation may play a role in the pathogenesis of irritable bowel syndrome. The aim of this study was to evaluate if dexamethasone (DEX) treatment prevents proteinase-activated receptor-2 (PAR-2) activation induced visceral hyperalgesia in rats, and to determine the role of PAR-2 and colonic mast cells in the effect of corticosteroid therapy.

Methods: Abdominal contractions provoked by rectal distension were recorded in rats. Changes in visceral hypersensitivity provoked by intracolonic administration of PAR-2 activating peptide (SLIGRL), colonic mucosal mast cell proteinase-II (RMCP-II) content, mast cell count and PAR-2 expression were measured after 4 days treatment with DEX (1mg/day/rat ip) or its vehicle (water). Effects of SLIGRL and mast cell degranulator (C48/80) on permeability of colonic strips from vehicle or DEX treated rats were investigated in Using chambers. Effect of short term DEX administration (3x during 24 hours) on mast cell degranulator (BRX537A) provoked visceral hyperalgesia was also determined.

Results: DEX treatment diminished the SLIGRL-induced hyperalgesia for all volumes of distension. This effect was coupled with reduced responsiveness for C48/80 on colonic permeability, decreased RMCP-II content and mast cell number. DEX treatment did not influence colonic mucosal PAR-2 expression and permeability responsiveness for SLIGRL. Short term DEX administration prevented the mast cell degranulator induced visceral hypersensitivity at distension volume of 0.4 mL.

Conclusion: Dexamethasone treatment attenuates PAR-2 agonist induced visceral hypersensitivity in rats through regulation of colonic mast cells.