polydatin relieves nociceptive pain: possible role of larginine/no/cgmp/katp channel signaling pathway in mice

Background :the role of the l-arginine (l-arg)/nitric oxide (no)/cyclic gmp (cgmp)/atp-sensitive potassium channel (katp) channel pathway in pain regulation is well-known. previous studies have confirmed the pain-relieving effects of polydatin, but the exact mechanisms behind anti-nociception are not fully understood. objectives :this study aimed to investigate how the l-arg/no/cgmp/katp channel pathway mediates the pain-relieving effects of polydatin in mice. methods :the formalin test was employed to assess nociceptive pain. mice were administered several compounds before receiving intraperitoneal doses of polydatin. the compounds included l-arg, a precursor of no; n(gamma)-nitro-l-arginine methyl ester (l-name), an inhibitor of no synthase; and s-nitroso-n-acetylpenicillamine (snap), a donor of no. additionally, glibenclamide, a blocker of the katp channel, and sildenafil, a phosphodiesterase inhibitor, were also administered. results :the results showed that intraperitoneal injection of polydatin at different doses (5, 10, and 15 mg/kg) led to dose-dependent and significant anti-nociception in both the early and late phases of the formalin test. the anti-nociceptive effects of polydatin were augmented when mice were pretreated with snap, while pretreatment with l-name and glibenclamide reduced these effects in the formalin test. conclusions :in conclusion, this study demonstrates the anti-nociceptive effect of polydatin and the involvement of the no/cgmp/katp channel pathway in such an effect.