Effect of cannabinoid receptor agonists on streptozotocin-induced hyperalgesia in diabetic neuropathy.

The effect of CB-1 and CB-2 receptor agonists, as well as an influence of a non-selective inhibitor of nitric oxide synthase (NOS), L-NOArg, and an inhibitor acting preferentially on cyclooxygenase-1 (COX-1), indomethacin, on the action of cannabinoid receptor agonists in a streptozotocin (STZ)-induced neuropathic model was investigated. When administered alone, a non-selective cannabinoid receptor agonist, WIN 55,212-2, a potentially selective CB-1 cannabinoid receptor agonist, Met-F-AEA, and a selective CB-2 cannabinoid receptor agonist, AM1241, dose-dependently reduced STZ-induced hyperalgesia. The results of the present study also demonstrated that inhibitors of COX and NOS increase antihyperalgesic activity of low doses of CB-1 and CB-2 receptor agonists. Hypothetical consequences of this phenomenon are discussed.