AU - Gercek, Oyku Zeynep AU - Oflaz, Busra AU - Oguz, Neslihan AU - Demirci, Koray AU - Gunduz, Ozgur AU - Ulugol, Ahmet TI - Role of Nitric Oxide in the Antipruritic Effect of WIN 55,212-2, a Cannabinoid Agonist PT - JOURNAL ARTICLE TA - BCN JN - BCN VO - 11 VI - 4 IP - 4 4099 - http://bcn.iums.ac.ir/article-1-1153-en.html 4100 - http://bcn.iums.ac.ir/article-1-1153-en.pdf SO - BCN 4 ABĀ  - 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 serotonin-induced 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. CP - IRAN IN - Trakya University, Faculty of Medicine, Department of Medical Pharmacology, 22030-Edirne, TURKEY LG - eng PB - BCN PG - 473 PT - Original YR - 2020