Background: Many women experience menstrual migraines that develop into recurrent migraine attacks during menstruation. In the human menstrual cycle, the estrogen level fluctuates according to changes in the follicular and luteal phases. The rat estrous cycle is used as an animal model to study the effects of estrogen fluctuation.
Objective: To investigate whether the estrous cycle is involved in migraine development by comparing the neuronal excitability
of trigeminal ganglion (TG) neurons in each stage of the estrous cycle.
Material and Method: Female rats were divided into four experimental groups based on examinations of the cytologies of
vaginal smears, and serum analyses of estrogen levels following each stage of the estrous cycle. The rats in each stage of the
estrous cycle were anesthetized and their trigeminal ganglia were removed. The collections of trigeminal ganglia were
cultured for two to three hours, after which whole-cell patch clamp experiments were recorded to estimate the electrophysiological properties of the TG neurons.
Results: There were many vaginal epithelial cells and high estrogen levels in the proestrus and estrus stages of the estrous
cycle. Electrophysiological studies revealed that the TG neurons in the proestrus and estrus stages exhibited significantly lower thresholds of stimulation, and significant increase in total spikes compared to the TG neurons that were collected in the diestrus stage.
Conclusion: Our results revealed that high estrogen levels in the proestrus and estrus stages altered the thresholds, rheobases, and total spikes of the TG neurons. High estrogen levels in the estrous cycle induced an increase in neuronal excitability and the peripheral sensitization of TG neurons. These findings may provide an explanation for the correlation of estrogen fluctuations during the menstrual cycle with the pathogenesis of menstrual migraines.

Keywords: Menstrual migraine, Peripheral sensitization, Estrous cycle, Trigeminal ganglion (TG) neurons, Whole-cell patch clamp recording