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

Background and Objectives: 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. Objectives: 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, GR۱۱۳۸۰۸, WAY ۱۰۰۶۳۵, 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 ۵-HT۳ receptor antagonist at ۱ and ۱۰ mg completely reversed the KM-related antinociception. Furthermore, ketanserin (۵-HT۲A receptor antagonist) and GR۱۱۳۸۰۸ (۵-HT۴ receptor antagonist) both at ۱۰ mg reduced KM-related antinociception; however, ۵-HT۱A receptor antagonist WAY ۱۰۰۶۳۵ and ۵-HT۱B antagonist penbutolol did not decrease KM-related antinociception. All KM doses were not observed with a significant effect on locomotor activity or motor reactions. Conclusion: The results of the current study suggested that serotonergic receptors (i.e., ۵-HT۲A, ۵-HT۳, and ۵-HT۴) are effective in the KM antinociceptive activity in male rats.

Keywords:

Central nervous system , Kaempferol , Pain , Serotonin receptors