CONTRASTING ACTIONS OF INTRATHECAL U50,488H, MORPHINE, OR [D-PEN(2), D-PEN(5)] ENKEPHALIN OR INTRAVENOUS U50, 488H ON THE VISCEROMOTOR, RESPONSE TO COLORECTAL DISTENSION IN THE RAT

Background: Visceral sensations are an important component of many clinical pain states. It is apparent that intrathecal pain relief may be more effective if appropriate combinations of drugs rather than a single agent can be used. The purpose of this study was to examine the relative contribution of opioid receptor subtypes to visceral antinociception using colorectal distension as a visceral pain model. Methods: The minimum colorectal distending pressure necessary to evoke a visceromotor response (contraction of abdominal musculature) was determined before and after the administration of opioid agonists for the mu (morphine), delta ([D-Pen(2), D-Pen(5)] enkephalin [DPDPE]), and kappa (U50,488H) opioid receptors. In addition to the three drug administered intrathecally, U50,488H was also administered intravenously. Results: Morphine and DPDPE produced a reversible increase in threshold for activation of the visceromotor response (50% maximum possible effect [MPE] at intrathecal doses of 2.2 and 16.4 mu g, respectively). The maximum intrathecal dose of U50,488H (100 mu g) produced only a 20% MPE. Intravenous U50,488H produced a 50% MPE at a dose of 2.6 mg/kg. Conclusions: The results suggest that spinal mu- and delta- but not kappa-opioid receptors have a significant role in the modulation of visceral nociception induced by coloretal distension. In addition, the results indicate that activation of nonspinal kappa receptors may mediate visceral antinociception.