Kappa-opioid receptor-mediated thermonociceptive mechanisms in streptozotocin diabetes

The effects of the benzomorphan kappa-opiate antagonist MR 2266 and its dextro enantiomer MR 2267 were assessed on thermonociception in male Swiss Webster mice. Experimental diabetes was induced by injecting streptozotocin (200 mg/kg IP, 7-8 days before). Animals with dextrose treatment (5 g/kg, IP, at the time of opiate injection) were used as acute hyperglycemic controls. Nociception was assessed by supraspinal nociceptive reflex (licking and jumping in hot plate test) indicative of higher cognitive process as well as a predominantly lower spinal monosynaptic reflex (tail immersion test). In normoglycemic, acute hyperglycemic and diabetic mice, MR 2266 decreased, while MR 2267 increased, the reaction latencies. The results indicate tonic stereospecific kappa-opiate receptor-mediated spinal and supraspinal thermonociceptive reactions are not modulated by experimental diabetes and thus are distinct from those of naloxone-sensitive mu-opiate receptor sites.