Peripheral Analgesic Effect and Possible Mechanisms of Ferulic Acid

Abstract

Ferulic acid is a bioactive phenolic compound that is found intensely in plants used in traditional medicine such as Ferula assa-foetida L.. The analgesic effect of various medicinal plants has been associated with its constituent, ferulic acid. However, there are limited number of studies about mechanism of its analgesic action. The aim of this study was to evaluate the contribution of NO/cGMP/PKG/KATP pathway in peripheral analgesic effect of ferulic acid by acetic acid-induced (0.6 % acetic acid, i.p.) writhing test in mice. For this purpose, following the determination of the analgesic effect of ferulic acid at the doses of 20, 40, 80 and 160 mg/kg (p.o.), 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.) were administered separately prior to ferulic acid treatment at the dose effective for clarifying the mechanism of action. Reduction in the number of writhes was evaluated as peripheral analgesic activity. Ferulic acid significantly decreased the number of writhes at the doses of 40, 80 and 160 mg/kg. 80 mg/kg ferulic acid and 100 mg/kg acetyl salicylic acid demonstrated similar efficacy. L-arginine and methylene blue relatively reversed the reduction in the number of writhes caused by ferulic acid at 80 mg/kg, whereas L-NAME did not. Glibenclamide pre-treatment significantly inhibited analgesic effect induced by ferulic acid. The results of the study indicate that ferulic acid has peripheral analgesic activity and it is mediated predominantly by activation of KATP channels and partially by cGMP. In conclusion, findings of this study demonstrate that ferulic acid may provide an advantage in KATP channel-targeted management of pain.