Kappa, but not mu or delta, opioids attenuate responses to distention of afferent fibers innervating the rat colon.
OBJECTIVE
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.
Sengupta
J N
JN
Department of Pharmacology, College of Medicine, University of Iowa, Iowa City, USA.
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Gebhart
G F
GF
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000344:Afferent Pathways / Q000502:physiology*; D000818:Animals; D001593:Benzyl Compounds / Q000494:pharmacology; D003106:Colon / Q000294:innervation*; D005283:Fentanyl / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology; D011437:Propylamines / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000502:physiology*; D017473:Receptors, Opioid, kappa / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000502:physiology*
D001593:Benzyl Compounds; D011437:Propylamines; D011759:Pyrrolidines; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; C067749:fedotozine; D005283:Fentanyl