Modification of κ-opioid receptor agonist-induced antinociception by diabetes in the mouse brain and spinal cord

The supraspinal and spinal antinociceptive effects of several κ-opioid receptor agonists were examined in diabetic and non-diabetic mice using the tail-flick assay. The antinociception induced by intrathecal (i.t.), but not intracerebroventricular (i.c.v.), CI-977, a highly selective κ-opioid receptor agonist, in diabetic mice was less than that in non-diabetic mice. The antinociceptive effects of ICI-199,441 and R-84760, high potency κ₁-opioid receptor agonists, given i.c.v., but not i.t., were attenuated in diabetic mice compared to those in non-diabetic mice. On the other hand, the antinociceptive effects of the new κ-opioid receptor agonist TRK-820, which has high affinity for κ₂- and/or K₃-opioid receptors, injected both i.c.v. and i.t. in diabetic mice were markedly less than those in non-diabetic mice. These results indicate that the antinociceptive effects of those κ-opioid receptor agonists in diabetic mice are altered in a region-specific manner in the central nervous system (CNS). The dysfunction of κ-opioid receptor subtypes in diabetic mice may underlie this CNS region-specific variation in the effects of these κ-opioid receptor agonists.