J N Sengupta1, X Su, G F Gebhart. 1. Department of Pharmacology, College of Medicine, University of Iowa, Iowa City, USA.
Abstract
BACKGROUND & AIMS: Discomfort and pain are the principal conscious sensations that arise from the viscera, and both are increased in frequency and intensity in patients with a functional bowel disorder. Visceral receptors, perhaps sensitized, may contribute to these altered sensations. The aim of this study was to evaluate the effects of opioid receptor-selective agonists on afferent fibers innervating the colon. METHODS: Mechanosensitive pelvic nerve afferent fibers were recorded from the decentralized S1 dorsal root in anesthetized rats. The effects of opioid agonists, given intra-arterially, were studied based on the fiber's responses to noxious colorectal distention (CRD) (80 mm Hg, 30 seconds). RESULTS: A total of 115 distention-sensitive fibers innervating the colon were studied, including 32 that were studied after colonic inflammation with 2.5% acetic acid. Neither mu-(morphine and fentanyl) nor delta- ([D-Pen2, D-Pen5]enkephalin- and SNC-80) opioid receptor agonists affected responses to CRD. In contrast, kappa- (U-50,488 and fedotozine) opioid receptor agonists dose-dependently attenuated responses to CRD. Acetic acid sensitized about half of the fibers studied, but neither the potency nor the efficacy of U-50, 488 or FDZ were changed after colonic inflammation. CONCLUSIONS: These results suggest a role for peripheral kappa-opioid receptors in the modulation of visceral nociception.
BACKGROUND & AIMS: Discomfort and pain are the principal conscious sensations that arise from the viscera, and both are increased in frequency and intensity in patients with a functional bowel disorder. Visceral receptors, perhaps sensitized, may contribute to these altered sensations. The aim of this study was to evaluate the effects of opioid receptor-selective agonists on afferent fibers innervating the colon. METHODS: Mechanosensitive pelvic nerve afferent fibers were recorded from the decentralized S1 dorsal root in anesthetized rats. The effects of opioid agonists, given intra-arterially, were studied based on the fiber's responses to noxious colorectal distention (CRD) (80 mm Hg, 30 seconds). RESULTS: A total of 115 distention-sensitive fibers innervating the colon were studied, including 32 that were studied after colonic inflammation with 2.5% acetic acid. Neither mu-(morphine and fentanyl) nor delta- ([D-Pen2, D-Pen5]enkephalin- and SNC-80) opioid receptor agonists affected responses to CRD. In contrast, kappa- (U-50,488 and fedotozine) opioid receptor agonists dose-dependently attenuated responses to CRD. Acetic acid sensitized about half of the fibers studied, but neither the potency nor the efficacy of U-50, 488 or FDZ were changed after colonic inflammation. CONCLUSIONS: These results suggest a role for peripheral kappa-opioid receptors in the modulation of visceral nociception.
Authors: Søren S Olesen; Jacob Juel; Carina Graversen; Yuri Kolesnikov; Oliver H G Wilder-Smith; Asbjørn M Drewes Journal: World J Gastroenterol Date: 2013-11-14 Impact factor: 5.742