Anti-nociceptive Activity of L-citrulline in Mice Using Formalin and Hot Plate Tests: Possible Mechanism of Action

Abstract

Background: Peripheral pain regulation is a very complex phenomenon due to the numerous neural pathways responsible for it. Objectives: The current study aimed to determine the anti-nociceptive activity of L-citrulline and the possible role of opioidergic, nitric oxide (NO), and serotoninergic systems in mice using the formalin and hot plate tests. Methods: In this study, 300 male NMRI mice were divided into 2 groups: 150 mice were used for the formalin test and 150 for the hot plate test (tests 1-6) with 4 sub-groups in each (n=50). The formalin test determined pain caused by the injection of formalin in the hind paw, and the hot plate test recorded pain reactions caused by heat stimulation as response latency time. Further, time mice capable of staying on the rotarod bar were determined. Results: Morphine reduced licking and biting time and latency time in the hot plate (P0.05. Conclusion: It seems that L-citrulline has anti-nociceptive effects, and its role is mediated by opioidergic, NO systems, as well as 5-HT2 and 5-HT3 receptors. Further, L-citrulline did not disturb motor coordination.

Keywords

• anti-nociceptive
• l-citrulline
• opioidergic
• nitric oxide
• serotoninergic