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• W4384661610 abstract "Abstract Background Migraine is more prevalent in females, raising the possibility that sex and gonadal hormones modulate migraine. We recently demonstrated that minimally invasive optogenetic spreading depolarization (opto-SD) elicits robust periorbital allodynia. The objective of this study was to test the hypothesis that opto-SD induced migraine-like pain behavior is worse in females and varies during the estrus cycle. Methods Single or repeated opto-SDs were induced in male and female adult Thy1-ChR2-YFP transgenic mice. Von Frey monofilaments were used to test periorbital mechanical allodynia. Mouse grimace was also examined under increasing light intensity to quantify spontaneous discomfort and light-aversive behavior. Vaginal smears were obtained for estrus cycle staging at the end of behavioral testing. Results A multi-variable regression analysis was performed using a male and female cohort to test the effect of independent variables on periorbital allodynia. Opto-SD predicted lower periorbital thresholds as compared with sham stimulation ( p < 0.0001). Additionally, female sex predicted lower periorbital thresholds compared with males ( p = 0.011). There were significant interactions between opto-SD and time (interaction p = 0.030) as animals tended to recover from opto-SD allodynia over time, and between sex and time ( p = 0.020) as females tended to take longer to recover. Proestrus, estrus (PE) and metestrus, diestrus (MD) stages were combined to represent high versus low circulating estradiol relative to progesterone, respectively. Multi-variable regression revealed an effect of estrus cycle ( p = 0.015) on periorbital thresholds. In the sham group, PE had lower thresholds than MD. However, there was no interaction between opto-SD and the estrus cycle ( p = 0.364). Grimace scores were also examined at incremental light intensities. There was an effect of opto-SD ( p < 0.0001), light intensity ( p = 0.001) and estrus cycle ( p = 0.024) on grimace without interaction among them (three-way ANOVA). Conclusions Female sex and estrus stages with high circulating estradiol relative to progesterone lower trigeminal pain thresholds and augment photosensitivity. In females, opto-SD increased pain behavior and photosensitivity irrespective of the estrus stage. Graphical Abstract" @default.
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• W4384661610 date "2023-07-19" @default.
• W4384661610 modified "2023-09-25" @default.
• W4384661610 title "The effect of sex and estrus cycle stage on optogenetic spreading depression induced migraine-like pain phenotypes" @default.
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• W4384661610 doi "https://doi.org/10.1186/s10194-023-01621-1" @default.
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• W4384661610 hasPublicationYear "2023" @default.
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