Distinct populations of sensory neurons mediate the peristaltic reflex elicited by muscle stretch and mucosal stimulation

Abstract

Recent studies suggest that muscle stretch and mucosal stimulation elicit intestinal peristalsis by activating distinct populations of sensory neurons that converge on the same population of enteric motor neurons. The present study sought to characterize the origin and projections of these sensory neurons. The reflex was elicited by applying muscle stretch and mucosal stroking to the central compartment of a three-compartment flat-sheet preparation of rat colon while ascending contraction and descending relaxation were measured in the orad and caudad compartments, respectively. Identical graded responses were elicited by muscle stretch and mucosal stimulation: atropine (1 μM) and the tachykinin antagonist spantide (10 μM) inhibited ascending contraction when added to the orad compartment only, while the vasoactive intestinal peptide antagonist VIP-10-28 (10 μM) and the NO synthase inhibitor N(G)-nitro-L-arginine (100 μM) inhibited descending relaxation when added to the caudad compartment only. Addition of capsaicin (1 μM) to the central compartment for 30 min abolished ascending contraction and descending relaxation elicited by muscle stretch and mucosal stimulation. Recovery of response was complete when capsaicin was applied to the mucosa of the colon in situ and measurements made 1 d after, implying that at this low concentration capsaicin depleted sensory nerve terminals of their transmitter content. Each of the following procedures, (1) excision of the inferior mesenteric ganglion, (2) application of 30 mM capsaicin to the ganglion for 30 min, (3) application of capsaicin followed by excision of the mesenteric ganglion, and (4) severing the fibers between the inferior mesenteric and dorsal root ganglia, all performed 2-3 weeks previously, abolished ascending contraction and descending relaxation elicited by muscle stretch but not by mucosal stimulation. Identical results were obtained in separate experiments in which muscle stretch was applied to intact whole colonic segments. Finally, removal of the mucosa had no effect on the responses to muscle stretch. The results demonstrate that sensory neurons activated by mucosal stimulation are wholly intrinsic, whereas sensory neurons activated by muscle stretch are extrinsic with cell bodies in the dorsal root ganglia and axonal projections to the motor limb of the reflex.