Visceral antinociceptive effects of spinal clonidine combined with morphine, [D-Pen2, D-Pen5] enkephalin, or U50,488H

Abstract

Background: Visceral pain is an important component of many clinical pain states. The perispinal administration of drug combinations rather than a single agent may reduce side effects while maximizing analgesic effectiveness. The purpose of this study was to examine the nature of interactions between an α2-adrenergic agonist (clonidine) and a μ-opioid agonist (morphine), a δ-opioid agonist ([D-Pen2, D-Pen5] enkephalin [DPDPE]), or a κ-opioid agonist (U50,488H). Methods: Colorectal distension was used to elicit a nociceptive visceromotor response (contraction of abdominal musculature) in rats. The ability of intrathecally administered clonidine alone or in combination with morphine, DPDPE, or U50,488H to alter thresholds for the production of the visceromotor response was examined. Results: Clonidine produced dose-dependent reduction in visceromotor response thresholds and, when combined with morphine or DPDPE, produced a synergistic reduction in the threshold. U50,488H, at the doses tested, showed no synergistic interaction with clonidine. Conclusions: Spinal combinations of α2-adrenergic and μ- or δ- but not κ-opioid agonists may be beneficial in the control of visceral pain.