Faculty Collaboration Database

Effects of kappa opioids in the inflamed rat colon. Pain 1999 Feb;79(2-3):175-85

Date

03/06/1999

Pubmed ID

10068163

DOI

10.1016/s0304-3959(98)00175-4

Scopus ID

2-s2.0-0033057419 (requires institutional sign-in at Scopus site)   126 Citations

Abstract

The objective of this study was to examine the antinociceptive effects of peripherally restricted kappa-opioid receptor agonists (ORAs) in a rat model of inflammatory bowel disease produced by intracolonic instillation of trinitrobenzine sulfonic acid (TNBS). Antinociceptive effects of mu-(morphine) and kappa-ORAs (EMD 61,753 and ICI 204,488) were evaluated in a behavioral model of visceral nociception. The effects of these agonists and a delta-ORA (SNC 80) on responses of pelvic nerve afferent fibers innervating the colon were also tested. In the behavioral study, systemic injections of morphine and both kappa-ORAs dose-dependently inhibited the visceromotor response to colorectal distension in rats with uninflamed or inflamed colons. The inhibitory effects of kappa-ORAs, but not morphine, were significantly greater in rats with colons inflamed 4 days previously by TNBS. A mu-receptor-selective dose (30 microg/kg) of naloxone methiodide (NLXM) blocked the inhibitory effect of morphine, but not of EMD 61,753. In the single-fiber study, neither morphine nor the delta-ORA SNC 80 attenuated the responses of pelvic nerve afferent fibers, whereas kappa-ORAs dose-dependently inhibited responses of pelvic nerve afferent fibers with significantly greater potency in the inflamed colon. Pretreatment with a non-opioid receptor-selective dose (2 mg/kg) of NLXM produced a rightward shift in the dose-response function of EMD 61,753. The greater potency of kappa-ORAs in the TNBS-inflamed condition suggests a peripheral upregulation of kappa-opioid receptors in colonic inflammation.

Author List

Sengupta JN, Snider A, Su X, Gebhart GF

Author

Jyoti N. Sengupta PhD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acetamides
Action Potentials
Analgesics, Opioid
Animals
Benzamides
Chronic Disease
Colitis
Colon
Electrophysiology
Male
Morphine
Naloxone
Narcotic Antagonists
Nerve Fibers
Neurons, Afferent
Pain Measurement
Piperazines
Pressure
Pyrrolidines
Rats
Rats, Sprague-Dawley
Receptors, Opioid, kappa
Rectum
Trinitrobenzenesulfonic Acid