Modification of kappa-opioid receptor agonist-induced antinociception by diabetes in the mouse brain and spinal cord.
The supraspinal and spinal antinociceptive effects of several kappa-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 kappa(1)-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 kappa(1)-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 kappa-opioid receptor agonist TRK-820, which has high affinity for kappa(2)- and/or kappa(3)-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 kappa-opioid receptor agonists in diabetic mice are altered in a region-specific manner in the central nervous system (CNS). The dysfunction of kappa-opioid receptor subtypes in diabetic mice may underlie this CNS region-specific variation in the effects of these kappa-opioid receptor agonists.
Ohsawa
Masahiro
M
Department of Pathophysiology and Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, Tokyo 142-8501, Japan.
Kamei
Junzo
J
D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D011759:Pyrrolidines / Q000494:pharmacology / Q000627:therapeutic use; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology
D000700:Analgesics; D001572:Benzofurans; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; C067110:enadoline