Date Published: January 25, 2019
Publisher: Public Library of Science
Author(s): Jun Sato, Hideaki Inagaki, Mayu Kusui, Makoto Yokosuka, Takahiro Ushida, Chang-Qing Gao.
Weather changes accompanied by decreases in barometric pressure are suggested to trigger meteoropathy, i.e., weather-related pain. We previously reported that neuropathic pain-related behavior in rats is aggravated by lowering barometric pressure, and that this effect is abolished by inner ear lesions. These results suggest that mechanisms that increase vestibular neuronal activity may parallel those that contribute to meteoropathy generation. However, it remains unknown whether changes in barometric pressure activate vestibular neuronal activity. To address this issue, we used expression of c-Fos protein as a marker for neural activation. Male and female mice were placed in a climatic chamber, and the barometric pressure was lowered by 40 hPa, from 1013 hPa, for 50 min (LP stimulation). The total number of c-Fos-positive cells in the vestibular nuclei was counted bilaterally after LP stimulation. We also video-recorded mouse behaviors and calculated the total activity score during the LP stimulation. LP stimulation resulted in significant c-Fos expression in the superior vestibular nucleus (SuVe) of male and female mice. There was no effect of LP stimulation on the total activity score. These data show that distinct neurons in the SuVe respond to LP stimulation. Similar mechanisms may contribute to the generation of meteoropathy in humans.
It has long been assumed that weather changes can trigger episodes of meteoropathy, such as headache and other forms of chronic pain [1–6]. Meteorological factors that influence pain include barometric pressure, humidity, wind, precipitation, and temperature [6–9]. We have previously demonstrated that lowering barometric pressure (5–27 hPa lower than atmospheric pressure; LP stimulation) using a climatic chamber leads to increased pain-related behaviors in rats with chronic constriction injury (CCI)  and monoarthritic rats . We have also reported that the LP-induced increase in pain-related behaviors vanishes after drug-induced destruction of the inner ear in CCI rats . In another study, we extracellularly recorded neural activities in vestibular nuclei with a glass microelectrode and examined the effect of LP (40 hPa/ 8 min) in normal anesthetized rats. Seven out of 20 recorded vestibular neurons increased their discharge frequency upon LP stimulation . These results suggest that the barometric sensor/sensing system influencing nociceptive behavior during LP in CCI rats is located in the inner ear. However, it is not known whether changes in barometric pressure activate vestibular neuronal activity in mice. If so, mechanisms that increase vestibular neuronal activity may parallel those that contribute to the development of meteoropathy. To investigate this issue, in this study, we used the expression of the immediate early-gene c-Fos, as a marker for neuronal activity in the vestibular nuclei and found that distinct vestibular neurons indeed respond to LP stimulation.
We examined whether LP stimulation induced neural activation in the vestibular nuclei. For this analysis, vestibular nuclear segments were immunohistologically examined for c-Fos protein, a marker of neuronal activation. The photomicrographs in Fig 2 were taken from SuVe and LVe sections bilaterally (SuVe: A and B, LVe: C and D) from male mice exposed to the LP stimulation (A1, B1, C1, and D1) or to control conditions (A2, B2, C2, and D2). The photomicrographs in Fig 3 were taken from SpVe and MVe sections bilaterally (A and B) from male mice exposed to the LP stimulation (A1 and B1) or to control conditions (A2 and B2). The tissues were processed for c-Fos immunostaining. As shown in Fig 2, we found c-Fos immunoreactivity in some SuVe cells after LP stimulation (A1 and B1), but little or no immunoreactivity was observed under control conditions (A2 and B2). Fig 4 shows the average number of c-Fos-immunopositive cells for each vestibular nucleus. This number was significantly increased in the SuVe of mice of both sexes exposed to LP stimulation. Two-way ANOVA revealed a significant effect of barometric pressure (F1, 30 = 9.76, p < 0.01) but not sex, and no significant interaction between the two factors. Post hoc analysis indicated that LP stimulation significantly increased the average number of c-Fos-positive cells in the SuVe (p < 0.01). In other vestibular nuclei, namely in the LVe, MVe, and SpVe, the number of c-Fos-immunopositive cells in each nucleus was not affected by barometric pressure or sex (two-way ANOVA, p > 0.05).
This is the first study investigating the impact of barometric pressure changes on neuronal activity in the vestibular nuclei in mice. The rationale of the present study was to examine if changes in barometric pressure within a range of natural weather changes may influence the activity of second-order neurons in the vestibular nuclei of mice, particularly of neurons receiving vestibular afferent input. Our present data clearly demonstrate that distinct neurons in the SuVe respond to LP stimulation. These data are consistent with our previous observation that some vestibular neurons in rats increased their discharge frequency upon LP stimulation .