Effects of kappa opioids in the inflamed rat colon

Pain. 1999 Feb;79(2-3):175-85. doi: 10.1016/s0304-3959(98)00175-4.


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.

Publication types

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

MeSH terms

  • Acetamides / therapeutic use
  • Action Potentials / drug effects
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / therapeutic use*
  • Animals
  • Benzamides / therapeutic use
  • Chronic Disease
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis / psychology
  • Colon / innervation
  • Colon / physiopathology
  • Electrophysiology
  • Male
  • Morphine / therapeutic use
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Nerve Fibers / drug effects
  • Nerve Fibers / pathology
  • Neurons, Afferent / drug effects
  • Pain Measurement
  • Piperazines / therapeutic use
  • Pressure
  • Pyrrolidines / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid, kappa / agonists
  • Receptors, Opioid, kappa / drug effects*
  • Rectum / physiopathology
  • Trinitrobenzenesulfonic Acid


  • Acetamides
  • Analgesics, Opioid
  • Benzamides
  • Narcotic Antagonists
  • Piperazines
  • Pyrrolidines
  • Receptors, Opioid, kappa
  • 4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide
  • Naloxone
  • Morphine
  • Trinitrobenzenesulfonic Acid
  • asimadoline