Pergamon Pharmacology Biochemistry and Behavior, Vol. 52, No. 3, pp. 561-563, 1995 Copyright o 1995 Elwier Science Inc. Printed in the USA. All rights reserved 0091-3057195 $9.50 + .oo owl-3057(95)00140-9 Oxymorphone-Induced Analgesia and Colonic Motility Measured in Colorectal Distension SHANNON L. BRIGGS,’ DONALD C. SAWYER, RICHARD H. RECH AND JAMES J. GALLIGAN Department of Pharmacology, Michigan State University, East Lansing, MI 48824 Received 29 August 1994 BRIGGS, S. L., D. C. SAWYER, R. H. RECH AND J. J. GALLIGAN. Oxymorphone-induced analgesia and co- Ionic motility measured in colorectal distension. PHARMACOL BIOCHEM BEHAV 52(3) 561-563, 1995. -Changes in colonic motility in rats following intravenous (IV) oxymorphone (0.1 mg/kg), atropine (0.1 mg/kg), or saline were monitored to determine whether opioid-induced changes in colonic motility affect antinociceptive measurements when using colorectal distension (CRD) as a nociceptive assay. Polygraph recordings of colonic pressures, contraction frequencies, and the pressure- volume relationship of the stimulus showed that oxymorphone produced a transient increase in contraction frequencies when compared to atropine- and saline-treated rats. The transient increase in contraction frequency caused by oxymorphone declined to baseline levels at 30 min after administration, the time at which the nociceptive threshold for CRD was tested. Neither oxymorphone nor a&opine changed baseline pressures or the pressure-volume curve for the balloon stimulus. Antino- ciceptive results from CRD at 30 min posttreatment showed that only oxymorphone produced significant antinociception. We conclude that oxymorphone does not produce changes in colonic motility that complicate antinociceptive measurements in CRD and that CRD is an effective means of testing opioid-induced visceral antinociception. Colorectal distension Visceral antinociception Oxymorphone Atropine DISTENDING hollow organs, such as the colon, is a means of studying visceral nociception in a variety of species (1,s ,8- 10,13-15). Studies using CRD in testing opioids or other anti- nociceptive agents generally have not included data regarding how colonic motility may affect meaurements of antinocicep- tion. Mu opioids are known to produce effective antinocicep- tion as well as powerful effects on gastrointestinal motility (3,9,12,16). Thus, when using CRD as a nociceptive assay in testing opioids, especially p opioids, it is important to know how these agents affect the distensibility of the colon, i.e., elastic and contractile properties of the colon. If opioids relax the colon and increase distensibility at the time when antinoci- ceptive measurements are taken, then those measurements may be misleading. In addition, an increase in the threshold pressure stimulus following opioid treatments could be due to the increased distensibility of the colon and not a true antino- ciceptive effect. If the colon is affected by ~1 opioids in this manner, then CRD may not be appropriate as a nociceptive assay, because opioids may be creating an apparent antinoci- ceptive effect by increasing the colonic diameter. On the other hand, if colonic motility is not changed by opioids, then CRD would be useful as a nociceptive assay. These studies were done to assess changes in colonic motility caused by oxymor- phone to determine whether oxymorphone had changed co- ionic motility at a time when antinociceptive measurements were made. METHODS Su bjecfs Five Harlan Sprague-Dawley rats (480-590 g), trained for the CRD protocol, randomly received one IV dose of each of the following treatments: atropine sulfate (0.1 mg/kg; The Butler Company, Columbus, OH), oxymorphone hydrochlo- ride (0. I mg/kg; Numorphan; DuPont Pharmaceuticals, Ma- nati, Puerto Rico), and saline (control). All drugs were admin- istered in a blinded manner. The dose of atropine was selected for its gastrointestinal effects (4,17) and the dose of oxymor- ’ Requests for reprints should be addressed to S. L. Briggs, B-300 Life Sciences, Michigan State University, East Lansing, MI 48824-1317. 561