[P1-3-27] Effects of topical application of menthol on nociceptive behaviors in the oral region of rats
Keywords:メントール、TRPM8、鎮痛
Menthol is added to various medicines for pain relief. However, the mechanism of its action is unclear. It has been suggested that activation of TRPM8, known as a menthol and cold receptor, mediates both analgesia and nociception. To investigate the role of TRPM8 in pain in the oral region, we examined effects of topical application of menthol on nociceptive behaviors in rats. Wild-type male Wistar rats (300-500 g) were used for experiments. Menthol (1 M,100 mM,10 mM), AITC(100 mM), and capsaicin(100 μM) were used as stimulants, and 1% DMSO was used as a control. A drop of the stimulants was applied on the labial fornix region of the inferior incisors of the rats. Immediately after the dropping, mouth rubbing by both fore-limbs was observed for 5 min as a pain-related behavior. To examine the analgesic effects of menthol, menthol and capsaicin or AITC were applied simultaneously. Since TRPA1 is activated by menthol, we performed the same experiments for TRPA1 knockout male rats. The application of low concentrations of menthol (10 and 100 mM) did not prolong the rubbing time. Simultaneous application of the low concentrations of menthol with capsaicin, an agonist of TRPV1, significantly inhibited capsaicin-induced prolongation of rubbing time, but not with AITC, an agonist of TRPA1. The results suggested that activation of TRPM8 by low concentrations of menthol inhibit TRPV1-mediated pain. Contrary to the low concentration, the application of 1 M menthol significantly prolonged the rubbing time compared with control groups. Since the prolonged rubbing time was not observed in the TRPA1 knockout mice, the increased rubbing behavior was mediated by activation of TRPM8. Our results suggest that activation of TRPM8 by high and low concentrations of menthol induces nociception and analgesic effects, respectively.