Rats with experimental
colitis suffer from impaired gastric emptying (GE). We previously showed that this phenomenon involves afferent neurons within the pelvic nerve. In this study, we aimed to identify the mediators involved in this afferent hyperactivation.
Colitis was induced by trinitrobenzene
sulfate (TNBS) instillation. We determined GE, distal front, and geometric center (GC) of intestinal transit 30 min after intragastric administration of a semiliquid
Evans blue solution. We evaluated the effects of the transient receptor potential vanilloid type 1 (TRPV1) antagonists
capsazepine (5-10 mg/kg) and N-(4-tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl)tetrahydropyrazine-1(2H)carboxamide (BCTC; 1-10 mg/kg) and the
calcitonin gene-related peptide (
CGRP) receptor antagonist CGRP-(8-37) (150 microg/kg). To determine
TRPV1 receptor antagonist sensitivity, we examined their effect on
capsaicin-induced relaxations of isolated gastric fundus muscle strips. Immunocytochemical staining of TRPV1 and RT-PCR analysis of TRPV1
mRNA were performed in dorsal root ganglion (DRG) L6-S1. TNBS-induced
colitis reduced GE but had no effect on intestinal motility.
Capsazepine reduced GE in controls but had no effect in rats with
colitis. At doses that had no effects in controls, BCTC and
CGRP-(8-37) significantly improved
colitis-induced
gastroparesis.
Capsazepine inhibited
capsaicin-induced relaxations by 35% whereas BCTC completely abolished them. TNBS-induced
colitis increased TRPV1-like immunoreactivity and TRPV1
mRNA content in pelvic afferent neuronal cell bodies in DRG L6-S1. In conclusion, distal
colitis in rats impairs GE via sensitized pelvic afferent neurons. We provided pharmacological, immunocytochemical, and molecular
biological evidence that this sensitization is mediated by TRPV1 receptors and involves CGRP release.