Contrasting actions of intrathecal U50,488H, morphine, or [D-Pen2, D-Pen5] enkephalin or intravenous U50,488H on the visceromotor response to colorectal distension in the rat.

Abstract

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. 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-Pen2, D-Pen5] enkephalin [DPDPE]), and kappa (U50,488H) opioid receptors. In addition to the three drugs administered intrathecally, U50, 488H was also administered intravenously. 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 micrograms, respectively). The maximum intrathecal dose of U50,488H (100 micrograms) produced only a 20% MPE. Intravenous U50,488H produced a 50% MPE at a dose of 2.6 mg/kg. 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 colorectal distension. In addition, the results indicate that activation of nonspinal kappa receptors may mediate visceral antinociception.