ArticleCephalalgia : an international journal of headache2024
A male-specific mechanism of meningeal nociceptor sensitization promoting migraine headache.
Article in Cephalalgia : an international journal of headache, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Sex-specific management of migraine a systematic review and consensus statement from the European Headache Federation (EHF).The journal of headache and pain · 2026Pooled it
- Review
- Article
- The therapeutic pipeline in migraine: What does the future hold?Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Pathogenic Role of FGFR3 Autoantibodies in Small Fiber Neuropathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Emerging pharmacological targets in migraine therapy: CGRP and beyond.Frontiers in pharmacology · 2026Review
- Up-regulation of peripheral and central CGRP expression combined with subchondral bone remodeling in rat MIA-induced TMJOA model.Journal of oral & facial pain and headache · 2025Article
- The role and interaction of hypothalamic-related neurotransmitters in migraine.The journal of headache and pain · 2025Review
- Chronification of migraine sensitizes to CGRP in male and female mice.Cephalalgia : an international journal of headache · 2025Article
- Article
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Authors and funding
8 authors.
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Abstract
backgroundWe wished to explore possible sexual dimorphism in mechanisms sensitizing or activating meningeal nociceptors that can promote the headache phase of migraine.
methodsMale and female C57BL6J mice received either supradural orexin B and an inflammatory mediator cocktail (IM) with migraine-like pain behaviors and photophobia recorded. Expression of orexin 2 receptor (OX2R) in trigeminal ganglion (TG) and phosphorylated extracellular signal-regulated kinases (ERK) levels in trigeminal nucleus caudalis (TNC) were evaluated. Orexin B-induced excitability of TG cells was assessed with patch-clamp electrophysiology. Intranasal delivery of CRISPR/Cas9 plasmids was used to edit the expression of OX2R in the TG.
resultsSupradural orexin B induced migraine-like pain behaviors, photophobia and increased TNC ERK phosphorylation exclusively in males. Blockade of orexin signaling with supradural suvorexant, a dual orexin receptor antagonist, prevented, but did not reverse, migraine-like pain in males induced by supradural IM cocktail. OX2R expression was higher in male TG and orexin B increased TG neuron excitability in males. Intranasal OX2R CRISPR/Cas9 reduced TG receptor expression and orexin B-induced TNC ERK phosphorylation and prevented migraine-like pain induced by supradural orexin B in males.
conclusionsOur studies reveal a male-specific mechanism of TG nociceptor sensitization and migraine-like pain behavior mediated by orexin B/OX2R signaling. Sexually dimorphic mechanisms of trigeminal nociceptor sensitization and activation offer opportunities to improve patient outcomes by considering patient sex and may influence clinical trial design and interpretation.
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