ArticleThe journal of headache and pain2023
The effect of sex and estrus cycle stage on optogenetic spreading depression induced migraine-like pain phenotypes.
Article in The journal of headache and pain, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 21 citations in OpenAlex.
- Cochlear Functional Changes and CGRP Modulation in a Chronic Nitroglycerin Migraine-Like Rat Model.The European journal of neuroscience · 2026Article
- Intranasal hybrid nanoparticles encapsulating rizatriptan enhance antimigraine efficacy in an optogenetic spreading depression model.International journal of pharmaceutics · 2026Article
- Tsunamis hiding in plain sight: spreading depression in clinical neurology.Nature reviews. Neurology · 2026Review
- The pPVTThe journal of headache and pain · 2026Article
- Spreading depolarization activates the cGAS-STING pathway and drives cranial nociception: therapeutic potential of STING modulation.The journal of headache and pain · 2026Article
- Is canonical SD a clinically relevant model of migraine? Argument pro.The journal of headache and pain · 2025Review
- Is canonical SD a clinically relevant model of migraine? Argument con.The journal of headache and pain · 2025Review
- Altered expressions of CGRP, SULT1A1, HMGB1, and HIF-1α in the trigeminal ganglion in medication overuse headache in female rats.The journal of headache and pain · 2025Article
- Spreading depolarization as a therapeutic target in migraine.Nature reviews. Neurology · 2025Review
- Oral atogepant mitigates spreading depolarization-induced pain and anxiety behavior in mice.The journal of headache and pain · 2025Article
- The mysterious link between migraine aura and migraine headache.PLoS biology · 2025Article
- Progesterone receptors regulate susceptibility to spreading depression.Experimental neurology · 2025Article
- Article
- Oxytocin shortens spreading depolarization-induced periorbital allodynia.The journal of headache and pain · 2024Article
- The Influence of Sex Steroid Hormone Fluctuations on Capsaicin-Induced Pain and TRPV1 Expression.International journal of molecular sciences · 2024Article
- Impacts of sex differences on optogenetic, chemogenetic, and calcium-imaging tools.Current opinion in neurobiology · 2024Review
- Assessing the association between age at first sexual intercourse and migraine: a Mendelian randomization study.Frontiers in neurology · 2024Article
- Medication overuse headache is associated with elevated lipopolysaccharide binding protein and pro-inflammatory molecules in the bloodstream.The journal of headache and pain · 2023Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundMigraine 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.
methodsSingle 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.
resultsA 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).
conclusionsFemale 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.
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