Menthol inhibits the respiratory rhythm in brainstem preparations of the newborn rats.

Menthol is known as an agonist for cold-sensitive transient receptor potential channels (TRPM8) and also as a direct modulator of GABA channels. We examined the effects of menthol on respiratory rhythm generation in the brainstem-spinal cord preparations isolated from newborn rats. Menthol decreased respiratory rhythm dose-dependently (0.1-1 mM). Effects of menthol were reversed by the GABAA antagonist, bicuculline. Menthol caused pronounced reduction in the driving potential of pre-inspiratory but not inspiratory neurons. Expression of the TRPM8 channel protein was not detected in the respiratory related region of the rostral ventrolateral medulla by immunohistochemistry. The results suggest that the potent inhibitory action of menthol on burst generation of pre-inspiratory neurons is because of direct activation of tonic GABA channels by menthol.