PT645. The Opiodergic, Serotonergic and Noradrenergic Modulation of Ferulic Acid-Induced Central Analgesia

Ferulic acid is a caffeic acid derivative and a common phenolic compound quite abundant in various medicinal plants that used for pain relief. The antinociceptive effect of ferulic acid has been shown; however, the action mechanisms of ferulic acid still remain unclear. The purpose of the present study was to investigate the possible mechanism of action of ferulic acid-induced antinociception in vivo by using hot-plate and tail-immersion tests. The involvement of noradrenergic, serotonergic, opioidergic and cholinergic mechanisms on the antinociception induced by 80 mg/kg ferulic acid were investigated by examining the effects of 1 mg/kg yohimbine as an α2-adrenoceptor antagonist, 1 mg/kg ketanserin as a serotonin 5-HT2A/2C receptor antagonist, 5 mg/kg naloxone as a non-specific opioid antagonist, 5 mg/kg atropine as a nonspecific muscarinic antagonist and 1 mg/kg mecamylamine as a non-specific nicotinic antagonist pretreatments in mice. Ferulic acid at the doses of 80 mg/kg (p.o.) produced an antinociception in hot-plate tests and at the doses of 40 and 80 mg/kg in tail-immersion test. Yohimbine, naloxone, atropine and mecamylamine, but not ketanserin, reversed the antinociceptive effect of ferulic acid in hot-plate test while yohimbine, naloxone, atropine and mecamylamine, but not ketanserin, reversed the antinociception in tail-immersion test. These results indicated that ferulic acid possesses central antinociception through mechanisms that involve an interaction with supraspinal/spinal noradrenergic, opioidergic and spinal cholinergic systems, except serotonergic system. In particular, ferulic acid acts as μopioidergic agonists.