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Vol. 285, Issue 2, 707-715, May 1998
Department of Pharmacology, College of Medicine, Bowen Science
Building, The University of Iowa, Iowa City, Iowa
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 
morphine 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.
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