Role of Nitric Oxide in the Antipruritic Effect of WIN 55,212-2, a Cannabinoid Agonist

Basic and Clinical Neuroscience

ARTICLE

Gercek, Oyku Zeynep¹  Oflaz, Busra¹  Oguz, Neslihan¹  Demirci, Koray¹  Gunduz, Ozgur¹  Ulugol, Ahmet¹ 

[1] Department of Medical Pharmacology, Faculty of Medicine, Trakya University

关键词: Cannabinoid system;    Nitric oxide;    Pruritus;    Serotonin;    WIN 55;    212-2;   

DOI  :  10.32598/bcn.9.10.465

来源: Iran University of Medical Sciences

【 摘 要 】

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.

【 授权许可】

Unknown