ArticleCephalalgia : an international journal of headache2022
A prolactin-dependent sexually dimorphic mechanism of migraine chronification.
Article in Cephalalgia : an international journal of headache, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Prolactin and pain of endometriosis.Pharmacology & therapeutics · 2023Pooled it
- Peri-adolescent ethanol exposure differentially affects mechanical and thermal sensitivity in rats.The journal of pain · 2026Article
- The therapeutic pipeline in migraine: What does the future hold?Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Spinal glial cell derived extra-pituitary prolactin contributes to postoperative pain in females.Frontiers in aging neuroscience · 2026Article
- Macrophages and iNOS contribute to the effects of dural prolactin and repeated stress in mouse migraine models.The journal of headache and pain · 2025Article
- Dopamine and prolactin in migraine: Mechanisms and potential therapeutic targets.Journal of neuroendocrinology · 2025Review
- Symptoms of allodynia and pain thresholds amongst those with acute post-traumatic headache attributed to mild traumatic brain injury: a prospective, longitudinal study.The journal of headache and pain · 2025Article
- Article
- Symptoms of Allodynia and Pain Thresholds Amongst Those with Acute Post-Traumatic Headache Attributed to Mild Traumatic Brain Injury: A Prospective, Longitudinal Study.Research square · 2025Article
- A prolactin-targeting antibody to prevent stress-induced peripheral nociceptor sensitization and female postoperative pain.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The role and interaction of hypothalamic-related neurotransmitters in migraine.The journal of headache and pain · 2025Review
- Multi-omic integration with human DRG proteomics highlights TNFα signalling as a relevant sexually dimorphic pathway.bioRxiv : the preprint server for biology · 2025Article
- Chronification of migraine sensitizes to CGRP in male and female mice.Cephalalgia : an international journal of headache · 2025Article
- Prolactin-induced sensitization of trigeminal nociceptors promotes migraine co-morbidity in endometriosis.Cephalalgia : an international journal of headache · 2025Article
- Nociceptors are functionally male or female: from mouse to monkey to man.Brain : a journal of neurology · 2024Article
- A male-specific mechanism of meningeal nociceptor sensitization promoting migraine headache.Cephalalgia : an international journal of headache · 2024Article
- Role of HDAC5 Epigenetics in Chronic Craniofacial Neuropathic Pain.International journal of molecular sciences · 2024Review
- Female-selective mechanisms promoting migraine.The journal of headache and pain · 2024Review
- Understanding the Biological Relationship between Migraine and Depression.Biomolecules · 2024Review
- Prolactin and oxytocin: potential targets for migraine treatment.The journal of headache and pain · 2023Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveDetermination of possible sex differences in mechanisms promoting migraine progression and the contribution of prolactin and the prolactin long (PRLR-L) and short (PRLR-S) receptor isoforms.
backgroundThe majority of patients with chronic migraine and medication overuse headache are female. Prolactin is present at higher levels in women and increases migraine. Prolactin signaling at the PRLR-S selectively sensitizes nociceptors in female rodents, while expression of the PRLR-L is protective.
methodsMedication overuse headache was modeled by repeated sumatriptan administration in male and female mice. Periorbital and hindpaw cutaneous allodynia served as a surrogate of migraine-like pain. PRLR-L and PRLR-S isoforms were measured in the trigeminal ganglion with western blotting. Possible co-localization of PRLR with serotonin 5HT1B and 5HT1D receptors was determined with RNAscope. Cabergoline, a dopamine receptor agonist that inhibits circulating prolactin, was co-administered with sumatriptan. Nasal administration of CRISPR/Cas9 plasmid was used to edit expression of both PRLR isoforms.
resultsPRLR was co-localized with 5HT1B or 5HT1D receptors in the ophthalmic region of female trigeminal ganglion. A single injection of sumatriptan increased serum PRL levels in female mice. Repeated sumatriptan promoted cutaneous allodynia in both sexes but down-regulated trigeminal ganglion PRLR-L, without altering PRLR-S, only in females. Co-administration of sumatriptan with cabergoline prevented allodynia and down-regulation of PRLR-L only in females. CRISPR/Cas9 editing of both PRLR isoforms in the trigeminal ganglion prevented sumatriptan-induced periorbital allodynia in females.
interpretationWe identified a sexually dimorphic mechanism of migraine chronification that involves down-regulation of PRLR-L and increased signaling of circulating prolactin at PRLR-S. These studies reveal a previously unrecognized neuroendocrine mechanism linking the hypothalamus to nociceptor sensitization that increases the risk of migraine pain in females and suggest opportunities for novel sex-specific therapies including gene editing through nasal delivery of CRISPR/Cas9 constructs.
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