The estrous cycle modulates voltage-gated ion channels in trigeminal ganglion neurons

Migraines typically occur more frequently in women than men because of the effects of estrogen on both the frequency and severity of migraine attacks. Many women suffer from migraine attacks during menstruation, which are known as menstrual migraines. The pathophysiology of menstrual migraines can be explored by using the rat estrous cycle, which shows a cyclical fluctuation of estrogen level that resembles the menstrual cycle. The aim of this study was to investigate whether different stages of the estrous cycle are involved in migraine development by comparing the excitability of trigeminal ganglion (TG) neurons in four different stages of the estrous cycle by using action potential (AP) parameter assessments. The stages of the estrous cycle were identified by a vaginal smear and measuring the estrogen levels in collected blood. The proestrus and estrus stages had higher estrogen levels compared with the diestrus and metestrus stages. Whole-cell patch clamp recordings demonstrated that TG neurons in the proestrus and estrus stage had lower AP threshold, lower rheobase, higher AP height, shorter AP falling time and deeper afterhyperpolarization (AHP) depth. Hence, our results revealed that the high level of estrogen in the proestrus and estrus stage alters the AP properties of TG neurons. Estrogen may increase membrane excitability and the summation of cellular responses, which alters the AP properties. The alterations of the AP properties in the proestrus and estrus stage may relate to a modification of voltage-gated ion channels in TG neurons, which is a pathogenesis for menstrual migraine. No COI.