Role of neurokinin 3 receptors on responses to colorectal distention in the rat: Electrophysiological and behavioral studies

Background & Aims: Tachykinins contribute to the control of gastrointestina l motility and modulation of somatic and visceral pain. The role of neuroki nin (NK) B and NK3 receptors in visceral pain and gastrointestinal disorder s has not been determined. Methods: Using electromyographic recordings of b oth abdominal and colonic muscle and electrophysiological recordings of pel vic nerve afferent fibers, we studied drug effects on responses to colorect al distention. Results: In awake rats, intraperitoneal administration of th e NK3-receptor antagonist SR 142,801 reduced, whereas the NK3-receptor agon ist senktide increased, both the rectocolonic inhibitory reflex and abdomin al contractions produced by colorectal distention. In contrast, intracerebr oventricular administration of SR 142,801 increased the number of abdominal contractions without affecting the rectocolonic inhibitory reflex produced by colorectal distention. In a similar manner, intracerebroventricular inj ection of senktide diminished the number of abdominal contractions. In elec trophysiological experiments, SR 142,801 decreased responses of pelvic nerv e afferent fibers to colorectal distention. Responses of pelvic nerve fiber s to urinary bladder distention, however, were unaffected by SR 142,801. Co nclusions: These results suggest that peripheral NK3 receptors are involved in the mediation of both visceral nociception and gastrointestinal disorde rs. Also, central NK3 receptors seem to play a role in the modulation of vi sceral nociception.