Kappa, but not mu or delta, opioids attenuate responses to distention of afferent fibers innervating the rat colon

Gastroenterology. 1996 Oct;111(4):968-80. doi: 10.1016/s0016-5085(96)70064-1.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Afferent Pathways / physiology*
  • Animals
  • Benzyl Compounds / pharmacology
  • Colon / innervation*
  • Fentanyl / pharmacology
  • Male
  • Morphine / pharmacology
  • Propylamines / pharmacology
  • Pyrrolidines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid, delta / physiology*
  • Receptors, Opioid, kappa / physiology*
  • Receptors, Opioid, mu / physiology*


  • Benzyl Compounds
  • Propylamines
  • Pyrrolidines
  • Receptors, Opioid, delta
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Morphine
  • fedotozine
  • Fentanyl