Intraintestinal capsaicin transiently reduces CGRP-like immunoreactivity in rat submucosal plexus

Abstract

Intraintestinal infusion of the sensory neurotoxin, capsaicin, transiently abolishes behavioral responses to chemical stimulation of the intestine. This desensitizing action of capsaicin may be due to an action on CGRP-containing nerve terminals, which are postulated to serve a sensory function in the enteric plexuses. To determine whether intraintestinal capsaicin treatment alters CGRP-like immunoreactivity (CGRP-li) in the enteric plexuses, we performed immunohistochemical analyses of the small intestinal submucosal and myenteric plexuses of rats at various times after intestinal infusion of capsaicin (5 mg) or its vehicle. Intestinal capsaicin treatment, but not vehicle treatment, reduced CGRP-li, but not substance-P-like immunoreactivity (SP-li), in nerve fibers of the submucosal plexus. CGRP-li was reduced in submucosal interganglionic connectives and in nerve fibers associated with submucosal blood vessels. CGRP-li of submucosal connectives was reduced by 1 h post-infusion. Reduction of CGRP-li in the submucosal fibers also was pronounced 24 h after intraintestinal capsaicin treatment. By 48 h after intestinal capsaicin infusion, CGRP-li was not distinguishable from vehicle-treated animals. There were no consistent immunohistochemical changes in CGRP-li or SP-li in the myenteric plexus at any time. These results indicate that intestinal capsaicin selectively induces transient reduction of CGRP-li in nerve fibers of the submucosal plexus. The chronology of depletion and reappearance of CGRP-li is congruent with previously reported, transient impairment of sensory function observed following intestinal capsaicin infusion.