The participation of serotonergic and noradrenergic modulation in rosmarinic acid-induced analgesia

Rosmarinic acid is a polyphenol which has antioxidant, anti-inflammatory and neuroprotective properties. It has been showed that rosmarinic acid has an analgesic effect, however, the mechanism of action has not been sufficiently clarified. In the thesis, it was aimed to evaluate the central analgesic activity of 0.3, 1 and 3 mg/kg (p.o.) rosmarinic acid in mice by hot-plate and tail-immersion tests in a time depend manner, peripheral analgesic activity by acetic acid-induced writhing test and to research the role of serotonergic system by using ketanserin (1 mg/kg, i.p.), 5HT2A/2C receptor antagonist, and yohimbine (1 mg/kg, i.p.), α2-adrenergic receptor antagonist, on antinociception of rosmarinic acid. Antagonists were administrated 30 minutes prior test material. The enhanced withdrawal responses to thermal stimuli were observed 45 minutes after administration of 1 mg/kg rosmarinic acid; 30, 45 and 60 minutes after 3 mg/kg rosmarinic acid administration in hot-plate test; and also 45 and 60 minutes after 1 and 3 mg/kg rosmarinic acid administration in tail-immersion test. In writhing test, the number of writhing significantly decreased 45 minutes after the administration of 0.3, 1 and 3 mg/kg rosmarinic acid. The antinociception induced by rosmarinic acid was significantly reversed by ketanserin only in tail-immersion test while yohimbine reversed relatively in hot-plate and significantly in tail-immersion test. The number of writhes which is reduced by administration of rosmarinic acid were increased by yohimbine pre-treatment. Rosmarinic acid provides central and peripheral analgesic effects by modulating serotonergic and noradrenergic systems which are located in descending inhibitory pathway and also by stimulating peripheral noradrenergic system. Therefore, rosmarinic acid is a natural agent which can be used safely by one-self or as an adjuvant in pain management.