This study aimed to investigate the central antinociceptive effects of ferulic acid, a common phenolic compound found in various medicinal plants used for pain relief, and the contribution of cholinergic, serotonergic, opiopidergic and noradrenergic modulation in ferulic acid-induced antinociception. The hotplate (integrated supraspinal response) and tail-immersion (spinal reflex) tests were used to measure pain thresholds in mice. The involvement of noradrenergic, serotonergic, opioidergic, and cholinergic mechanisms in the antinociception induced by 80 mg/kg (po) ferulic acid were investigated by examining the effects of 1 mg/kg yohimbine as an alpha(2)-adrenoceptor antagonist, 1 mg/kg ketanserin as a serotonin 5-HT2A/2C receptor antagonist, 5 mg/kg naloxone as a nonspecific opioid antagonist, 5 mg/kg atropine as a nonspecific muscarinic antagonist, and 1 mg/kg mecamylamine as a nonspecific nicotinic antagonist pretreatments in mice. Ferulic acid at the doses of 80 mg/kg produced antinociception in hot-plate test and tail-immersion test. Yohimbine and naloxone, but not ketanserin, atropine and mecamylamine, remarkably reversed the antinociceptive effect of ferulic acid in hot-plate test while yohimbine, naloxone, atropine and mecamylamine, but not ketanserin, remarkably reversed the antinociception in tail-immersion test. These results indicated that ferulic acid induces central antinociception through mechanisms involving an interaction with supraspinal/spinal noradrenergic, opioidergic, and spinal cholinergic systems, excluding serotonergic system. All these modulatory systems manage the analgesic effect of ferulic acid with perfect coordination. Therefore, it seems that ferulic acid can be used in pain management as a coadjuvant or monotherapeutic agent.