Peripheral analgesic effect and possible mechanisms of ferulic acid

Ferulic acid is a bioactive phenolic with a limited number of studies showing the analgesic effect and mechanism of action. The aim of this study was to evaluate the peripheral analgesic efficacy of ferulic acid in the mice with writhing test induced by injection of 0,6% acetic acid, i.p., and to investigate the role of the NO/cGMP/PKG/KATP pathway in this activity. For this purpose, after the determination of the analgesic effect of ferulic acid in 20, 40, 80 and 160 mg/kg (p.o.) doses, NO precursor 100 mg/kg L-arginine (i.p.), nitric oxide synthase inhibitor 30 mg/kg L-NAME (i.p.), guanylate cyclase inhibitor 20 mg/kg methylene blue (i.p.) and KATP channel blocker 10 mg/kg glibenclamide (i.p.) was used separately before the ferulic acid applied at the dose effective for clarifying the mechanism of action. Reduction in the number of writhes was evaluated as analgesic activity. At the 40, 80 and 160 mg/kg doses, ferulic acid significantly decreased writhing numbers. It was determined that 80 mg/kg ferulic acid and 100 mg/kg acetyl salicylic acid had similar activity at close levels. Reduction in the number of writhes caused by ferulic acid at 80 mg/kg; while L-arginine and methylene blue were relatively reversed, L-NAME could not reverse. Glibenclamide pre-treatment significantly inhibited this reduction induced by ferulic acid. The results of the study indicate that ferulic acid has peripheral analgesic activity and this activity is mediated partially by sGMP but primarily by activation of KATP channels. In conclusion, it is possible to say that ferulic acid can be an effective agent for the treatment of pain alone or as an adjuvant. Keywords: Ferulic acid, Nitric oxide, Guanylate cyclase, KATP channels, Pain