EFFECT OF DIABETES ON THE ANTINOCICEPTIVE EFFECT OF BETA-ENDORPHIN

We examined whether streptozotocin-induced diabetes can modulate beta- endorphin-induced antinociception in mice. While beta-endorphin admini stered i.c.v. produced a dose-dependent inhibition of the tail-flick r esponse in both diabetic and non-diabetic mice, the antinociceptive re sponse was greater in diabetic mice than in non-diabetic mice. The ED5 0 value of beta-endorphin administered i.cv. in diabetic mice was sign ificantly lower than that in non-diabetic mice. The antinociceptive ef fects of beta-endorphin administered i.c.v. in both diabetic and non-d iabetic mice were significantly antagonized by s.c. administration of naltrindole, a selective delta-opioid receptor antagonist. Beta-Endorp hin administered i.t. also produced a dose-dependent antinociception i n both diabetic and non-diabetic mice. However, the ED50 value of beta -endorphin administered i.t. in diabetic mice was significantly higher than that in non-diabetic mice. The antinociceptive effect of beta-en dorphin administered i.t. in both diabetic and non-diabetic mice were significantly antagonized by s.c. administration of nor-binaltorphimin e, a selective kappa-opioid receptor antagonist. On the other hand, th e antinociceptive potency of DPDPE, a selective delta-opioid agonist, administered i.t. is significantly increased in diabetic mice, as comp ared with non-diabetic mice, whereas, the antinociceptive potency of U -50,488H, a kappa-opioid receptor agonist, administered i.t. is signif icantly less than in non-diabetic mice. These results suggest that dia betes may modulate beta-endorphin-induced antinociception differently at the spinal and supraspinal levels.