STREPTOZOTOCIN-INDUCED DIABETES SELECTIVELY ALTERS THE POTENCY OF ANALGESIA PRODUCED BY MU-OPIOID AGONISTS, BUT NOT BY DELTA-OPIOID AND KAPPA-OPIOID AGONISTS

To investigate the possible mechanisms of the alterations in morphine-induced analgesia observed in diabetic mice, we examined the influence of streptozotocin-induced (STZ-induced) diabetes on analgesia mediated by the different opioid receptors. The antinociceptive potency of morphine (10 mg/kg), administered s.c., as determined by both the tail-pinch and the tail-flick test, was significantly reduced in diabetic mice as compared to that in controls. Mice with STZ-induced diabetes had significantly decreased sensitivity to intracerebroventricularly (i.c.v.) administered mu-opioid agonists, such as morphine (10-mu-g) and [D-Ala2,N-Me Phe4,Gly-ol5]enkephalin (DAMGO, 0.5-mu-g). However, i.e.v. administration of [D-Pen2.5]enkephalin (DPDPE, 5-mu-g), a delta-opioid agonist, and U-50,488H (50-mu-g), a kappa-opioid agonist, produced pronounced antinociception in both control and diabetic mice. Furthermore, there were no significant differences in antinociceptive potency between diabetic and control mice when morphine (1-mu-g), DAMGO (10-mu-g), DPDPE (0.5-mu-g) or U-50,488H (50-mu-g) was administered intrathecally. In conclusion, mice with STZ-induced diabetes are selectively hyporesponsive to supraspinal mu-opioid receptor-mediated antinociception, but they are normally responsive to activation of delta- and kappa-opioid receptors.