role of nitric oxide in the antipruritic effect of win 55,212-2, a cannabinoid agonist

Introduction: for centuries, cannabinoids are known to be effective in pain relief. itch is an unpleasant sensation that provokes a desire to scratch. since itch and pain are two sensations sharing a lot in common, we aimed to investigate whether the cannabinoid agonist win 55,212-2 reduces serotonin-induced scratching behavior and also observe whether modulation of nitric oxide (no) production mediates the antipruritic effect of win 55,212-2. methods: scratching behavior is induced by intradermal injection of serotonin (50 μg/50 μl/mouse) to balb/c mice. the cannabinoid agonist win 55,212-2 (1, 3, 10 mg/kg, ip) was given 30 min before serotonin injection. to observe the effect of no modulation on the antipruritic effect of cannabinoids, the endothelial nitric oxide synthase (nos) inhibitor l-name (3 mg/kg, ip), the neuronal nos inhibitor 7-nitroindazole (3 mg/kg, ip), and the no precursor l-arginine (100 mg/kg, ip) were administered together with win 55,212-2. results: win 55,212-2 reduced serotonin-induced scratches at higher doses (3, 10 mg/kg; p<0.0001). the endothelial nos inhibitor l-name, the neuronal nos inhibitor 7-nitroindazole, and the nitric oxide precursor l-arginine did not influence the antipruritic action of win 55,212-2. when no modulators were used alone, only the neuronal nos inhibitor 7-nitroindazole attenuated serotonin-induced scratches (p<0.0001). conclusion: our findings indicate that exogenous cannabinoids may attenuate serotonininduced scratches and no does not mediate the antipruritic effect of win 55,212-2. on the other hand, neuronal nos inhibition may play a role in the production of serotonin-induced scratches.