ArticleThe journal of headache and pain2020
Estrogen receptors α, β and GPER in the CNS and trigeminal system - molecular and functional aspects.
Article in The journal of headache and pain, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- The progress and evolutionary direction of menstrual migraine research: a bibliometric analysis from 1994 to 2026.Frontiers in medicine · 2026Pooled it
- Oxytocin receptor antagonism in migraine: a randomized, double-blind, placebo-controlled provocation study.The journal of headache and pain · 2026Trial
- The Estrogen-CGRP Axis in Migraine: Neuroimmune Mechanisms, Sex Differences, and Therapeutic Implications.Molecular neurobiology · 2026Review
- Morning Headaches as a Specific Obstructive Sleep Apnea Characteristic in a Large Sleep Clinic Population.Life (Basel, Switzerland) · 2026Article
- Activation of the G-protein coupled estrogen receptor 1 (GPER1) reduces transient receptor potential vanilloid 1 (TRPV1) activity and human iPSC-derived nociceptive neuron firing.Stem cell research & therapy · 2026Article
- 17α-Estradiol: A mildly feminizing estrogen with sex-specific metabolic and lifespan benefits.Ageing research reviews · 2026Review
- Regenerative Medicine Approaches to Craniofacial and Corneal Neuropathic Pain.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Efficacy and safety of rimegepant in Chinese women with pure menstrual migraine: a retrospective observational study.BMC neurology · 2026Observational
- Not just neurons: glial mechanisms driving sex-specific vulnerability to withdrawal and relapse in substance use disorder.Frontiers in neuroendocrinology · 2026Review
- Hypothalamic and sex-related hormones in migraine.The journal of headache and pain · 2026Review
- Potential Roles of G Protein-Coupled Receptor 30 (GPR30) in Migraine Pathophysiology.Journal of pain research · 2026Review
- Modifying Factors of Adult Hippocampal Neurogenesis: A Dorsoventral Perspective in Health and Disease.Cells · 2025Review
- Expression of melatonin receptors in trigeminal and sphenopalatine ganglia: potential targets for primary headache disorders.The journal of headache and pain · 2025Article
- Chloroindazole based estrogen receptor β ligands with favorable pharmacokinetics promote functional remyelination and visual recovery.Scientific reports · 2025Article
- Estradiol Prevents Amyloid Beta-Induced Mitochondrial Dysfunction and Neurotoxicity in Alzheimer's Disease via AMPK-Dependent Suppression of NF-κB Signaling.International journal of molecular sciences · 2025Article
- RAMP1-dependent hormonal regulation of CGRP and its receptor in the trigeminal ganglion.The journal of headache and pain · 2025Article
- The role and interaction of hypothalamic-related neurotransmitters in migraine.The journal of headache and pain · 2025Review
- Advancing understanding of migraine pathophysiology and therapy by consideration of patient sex.Cephalalgia : an international journal of headache · 2025Review
- Relationship of Reduced Pain Intensity and Improved Quality-of-Life with Menstrual Migraine with Aspirin, Acetaminophen, and Caffeine Combination.Healthcare (Basel, Switzerland) · 2025Article
- Sexual Dimorphism in Migraine. Focus on Mitochondria.Current pain and headache reports · 2025Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundMigraine occurs 2-3 times more often in females than in males and is in many females associated with the onset of menstruation. The steroid hormone, 17β-estradiol (estrogen, E2), exerts its effects by binding and activating several estrogen receptors (ERs). Calcitonin gene-related peptide (CGRP) has a strong position in migraine pathophysiology, and interaction with CGRP has resulted in several successful drugs for acute and prophylactic treatment of migraine, effective in all age groups and in both sexes.
methodsImmunohistochemistry was used for detection and localization of proteins, release of CGRP and PACAP investigated by ELISA and myography/perfusion arteriography was performed on rat and human arterial segments.
resultsERα was found throughout the whole brain, and in several migraine related structures. ERβ was mainly found in the hippocampus and the cerebellum. In trigeminal ganglion (TG), ERα was found in the nuclei of neurons; these neurons expressed CGRP or the CGRP receptor in the cytoplasm. G-protein ER (GPER) was observed in the cell membrane and cytoplasm in most TG neurons. We compared TG from males and females, and females expressed more ER receptors. For neuropeptide release, the only observable difference was a baseline CGRP release being higher in the pro-estrous state as compared to estrous state. In the middle cerebral artery (MCA), we observed similar dilatory ER-responses between males and females, except for vasodilatory ERβ which we observed only in female arteries.
conclusionThese data reveal significant differences in ER receptor expression between male and female rats. This contrasts to CGRP and PACAP release where we did not observe discernable difference between the sexes. Together, this points to a hypothesis where estrogen could have a modulatory role on the trigeminal neuron function in general rather than on the acute CGRP release mechanisms and vasomotor responses.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.