TY - JOUR T1 - Effects of <em>Kappa</em>-Opioid Receptor Agonists on Responses to Colorectal Distension in Rats with and without Acute Colonic Inflammation JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 707 LP - 715 VL - 285 IS - 2 AU - Maureen B. Burton AU - G. F. Gebhart Y1 - 1998/05/01 UR - http://jpet.aspetjournals.org/content/285/2/707.abstract N2 - The objective of this study was to evaluate the effects ofkappa-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 &gt; U69,593 &gt; U50,488 ≥ morphine ≥ EMD61,753 &gt; 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 thatkappa-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. The American Society for Pharmacology and Experimental Therapeutics ER -