Possible Involvement of Serotonergic Mechanism(s) in the Antinociceptive Effects of kaempferol

Background and Objective: A flavonoid kaempferol (KM) exerts an anti-inflammatory effect and is reportedly capable of preventing metabolic diseases. Nonetheless, a limited number of studies have been carried out on the antinociceptive effects of kaempferol. The present study aimed to investigate the involvement of serotonin receptors in the antinociceptive-like activity of KM in male Wistar rats using the tail-flick test. Materials and Methods: The compounds (i.e., KM, morphine, and diclofenac) were intracerebroventricularly administered to rats for the examination of central effects on the thermal pain using the tail-flick test. For the evaluation of the involvement of serotonin receptors in the possible antinociceptive effects of kaempferol, several antagonists (i.e., tropisetron, ketanserin, GR113808, WAY 100635, and penbutolol) were used. Additionally, locomotor activity and motor responses were investigated by the rotarod test after KM treatment. Results: The intracerebroventricular microinjections of KM showed antinociceptive effects using the tail-flick test. The pretreatment with tropisetron as a 5-HT3 receptor antagonist at 1 and 10 μg completely reversed the KM-related antinociception. Furthermore, ketanserin (5-HT2A receptor antagonist) and GR113808 (5-HT4 receptor antagonist) both at 10 μg reduced KM-related antinociception; however, 5-HT1A receptor antagonist WAY 100635 and 5-HT1B antagonist penbutolol did not decrease KM-related antinociception. All KM doses were not observed with a significant effect on locomotor activity or motor reactions. Conclusions: The results of the current study suggested that serotonergic receptors (i.e., 5-HT2A, 5- HT3, and 5-HT are effective in the KM antinociceptive activity in male rats.