@article {Burton707, author = {Maureen B. Burton and G. F. Gebhart}, title = {Effects of Kappa-Opioid Receptor Agonists on Responses to Colorectal Distension in Rats with and without Acute Colonic Inflammation }, volume = {285}, number = {2}, pages = {707--715}, year = {1998}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {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 \> 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 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}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/285/2/707}, eprint = {https://jpet.aspetjournals.org/content/285/2/707.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }