The effect of intrathecal opioid-receptor agonists on visceral noxious stimulation in rabbits

Conflicting results have been published concerning the effects of different opioid-receptor agonists against visceral noxious stimulation. The introduction of colorectal distention facilitates research in this field. The aim of this study was to examine intrathecally administered opioid agonists against colorectal distention in conscious rabbits.

Rabbits were equipped with a subcutaneous intrathecal injection system. Colorectal distention was induced by inflation of a balloon inserted into the descending colon. The test parameter was the pressure eliciting a characteristic visceromotor response. Examinations were performed before and after administration of the following drugs: morphine, U50488H, [D-Pen2, D-Pen5]enkephalin (DPDPE), naloxone, MR2266, naltrindole, saline, and acidified saline.

The visceromotor response to colorectal distention was inhibited in a dose-dependent fashion by intrathecal opioids acting as agonists at all three types of opioid receptors. Morphine was antagonized more effectively by intrathecal than intramuscular naloxone. U50488H and DPDPE were equally antagonized by the specific antagonists MR2266 and naltrindole. Electrical thresholds in the lumbar region were increased, although they remained unaltered in the cervical region after administration of all three agonists.

Intrathecal administration of different opioid agonists produces a dose-dependent spinal effect. The rank order of potencies in this model is DPDPE > U50488H > morphine > saline = 0.