Send to

Choose Destination
See comment in PubMed Commons below
J Pharmacol Exp Ther. 1998 May;285(2):707-15.

Effects of kappa-opioid receptor agonists on responses to colorectal distension in rats with and without acute colonic inflammation.

Author information

Department of Pharmacology, College of Medicine, University of Iowa, Iowa City, USA.


The objective of this study was to evaluate the effects of kappa-opioid receptor agonists on pressor and visceromotor responses to colorectal distension in awake, unrestrained rats, a model of visceral pain. Because visceral pain can be enhanced in the presence of inflammation, the study was conducted in rats that had been given either intracolonic saline or 5% acetic acid 6 hr before drug administration. We developed a method of staircase colorectal distension as a means of obtaining stimulus-response functions over a short period of time. Kappa-opioid receptor agonists, given i.v. in a cumulative dose paradigm, dose-dependently attenuated both the pressor and visceromotor responses to colorectal distension. In addition, all drugs tested also increased response threshold. The rank order of potency of the drugs tested was: CI977 > U69,593 > U50,488 > or = morphine > or = EMD61,753 > ICI204,448. Effective doses of these drugs were antagonized by naloxone, but not by either of two kappa-opioid receptor-selective antagonists (nor-binaltorphimine and 2-(3,4-dichlorophenyl)-N-methyl-N-(1-[3-isothiocyanate phenyl]-2-[1-pyrrolidinyl]ethyl)-acetamide). Acute inflammation of the colon did not lead to changes in the potency of the agonists tested. The present results provide further evidence that kappa-opioid receptor agonists significantly attenuate visceral nociception and, in conjunction with other information, suggest that a peripherally restricted kappa-opioid receptor agonist would be therapeutically effective in relieving visceral pain.

[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons


    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center