The alternation pattern of estrous cycle modulating electrophysiological properties in primary-cultured trigeminal ganglia neurons

Abstract

Migraine occurs more frequently in women than men. Many women suffer from migraine attacks during menstruation, which are known as menstrual migraine. The aim of this study was to investigate whether different stages of the estrous cycle are involved in migraine development by comparing the excitability and sensitivity of trigeminal ganglion (TG) neurons in four different stages of the estrous cycle by using action potential (AP) parameter assessments performed with whole-cell patch clamp recordings. The result showed that TG neurons in the proestrus and estrus stage had lower AP threshold, lower rheobase, higher AP height, shorter AP falling time and deeper after-hyperpolarization (AHP) depth. In addition, The summation of AP development indicated that TG neurons in proestrus and estrus stages exhibited significantly lower thresholds and rheobase of stimulation, and significant increase of total spikes compared with the TG neurons in the diestrus stage. Our results revealed that fluctuation of estrogen levels in the proestrus and estrus stages altered the single AP properties and summation of AP development of TG neurons. High estrogen levels in proestrus and estrus stages of the estrous cycle may induce increases of neuronal excitability and sensitivity in TG neurons that result in modulation of voltage-gated ion channels and peripheral sensitization. These findings may provide an explanation for the correlation of estrogen fluctuations during the menstrual cycle with the pathogenesis of menstrual migraine.