Expression of Fos protein in brainstem after application of l-menthol to the rat nasal mucosa

There are two functional pathways for the nasotrigeminal reflex: the spinal nucleus of trigeminal nerve (SPV) to the Kölliker-Fuse (KF) nucleus and the nucleus of solitary tract (NTS) to the lateral parabrachial nucleus (PBl). Although stimulation of the nasal mucosa by cool temperature induces respiratory depression, it is still unknown whether these nuclei are activated. In the present study, we examined the expression of Fos protein in rat brainstem neurons after nasal application of l-menthol, which is known to activate cold-sensitive nasal receptors. Application of l-menthol, but not paraffin oil, decreased the respiratory rate from 99.7 ± 15.6 to 78.5 ± 7.3 min−1. Furthermore, a significantly higher density of Fos-immunoreactive cells was observed in the SPV and KF in the l-menthol rats than in the controls. In the SPV, the density of Fos-immunoreactive cells was highest at approximately 0.5 mm rostral to the obex in both the l-menthol (48.5 ± 11.5 cells/section) and paraffin oil (26.0 ± 9.6 cells/section) groups. In the KF, the mean density of Fos-immunoreactive cells was highest at approximately 5.0 mm rostral to the obex in both groups (l-menthol: 67.8 ± 14.0 cells/section, control: 41.0 ± 12.7 cells/section). The present study suggests that the SPV-KF pathway is important for the cold-induced respiratory depression.