The antinociceptive effects of endomorphin-1 and endomorphin-2 in diabeticmice

The antinociceptive effects of endomorphin-1 and endomorphin-2, endogenous mu-opioid receptor agonists, were examined using the tail-flick test in non -diabetic and diabetic mice. Endomorphin-1, at doses of 1 to 10 mu g, i.c.v ., and endomorphin-2, at doses of 3 to 30 mu g, i.c.v., each dose dependent ly inhibited the tail-flick response in both non-diabetic and diabetic mice . There was no significant difference between the antinociceptive effects o f endomorphin-1 in non-diabetic mice and diabetic mice. The antinociceptive effect of endomorphin-2 was greater in non-diabetic mice than in diabetic mice. In non-diabetic mice, the antinociceptive effects of endomorphin-1 an d endomorphin-2 were significantly reduced by beta-funaltrexanline, a mu-op ioid receptor antagonist, and naloxonazine, a selective mu(1)-opioid recept or antagonist, but not by naltrindole, a delta-opioid receptor antagonist, or nor-binaltorphimine, a kappa-opioid receptor antagonist. In diabetic mic e, the antinociceptive effect of endomorphin-3 was significantly reduced by beta-funaltrexamine and naloxonazine. However, these mu-opioid receptor an tagonists had no significant effect on the antinociceptive effect of endomo rphin-1 in diabetic mice. The antinociception induced by endomorphin-1 in d iabetic mice was significantly reduced by naltrindole and 7-benzylidenenalt rexon, a selective delta(1)-opioid receptor antagonist, administered i.c.v. However. nor-binaltorphimine had no significant effect on the antinocicept ive effects of endomorphin-1 and endomorphin-2 in diabetic mice. These resu lts indicate that the antinociceptive effects of endomorphin-1 and endomorp hin-2, in non-diabetic mice an mediated through the activation of mu(1)-opi oid receptors, whereas in diabetic mice, endomorphin-1 and endomorphin-2 ma y produce antinociception through different actions at delta(1)- and mu(1)- opioid receptors, respectively. (C) 2000 Elsevier Science B.V. All rights r eserved.