The Involvement of NO–cGMP–ATP Sensitive K+ Channels Pathway in Protocatechuic Acid Peripheral Analgesia

Protocatechuic acid (PCA) is a widely distributed natural bioactive phenolic acid. The various pharmacological activities such as antioxidant, antidiabetic and anti-inflammatory activities have been identified. However, the studies focused on the analgesic effect of protocatechuic acid are limited and the action mechanisms of PCA still remain unclear. The NO-cGMP-ATP-sensitive K+ channels pathway is one of the mechanism of action for various analgesic drugs. The present study was conducted to investigate the involvement of NO–cGMP–ATP sensitive K+ channels pathway in analgesic effect of p.o. administration of 300 mg/kg protocatechuic acid in acetic acid-induced writhing test in mice. It was shown that pre-treatment with glibenclamide (10 mg/kg, i.p.), an ATPsensitive K+ channel blocker, and methylene blue (20 mg/kg, i.p.), a guanylate cyclase inhibitor, did not notably change antinociception produced by 300 mg/kg protocatechuic acid, however administration of nitro-L-arginine methyl ester (10 mg/kg, i.p.), a nitric oxide synthase inhibitor, significantly reversed protocatechuic acid antinociception. The results show that the peripheral mechanism of action of protocatechuic acid-induced antinociception involved another nitric oxide related pain pathway, not NO–cGMP–ATP sensitive K+ channels pathway.