ArticleAnnals of neurology2016
Upregulation of inflammatory gene transcripts in periosteum of chronic migraineurs: Implications for extracranial origin of headache.
Article in Annals of neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 88 citations in OpenAlex.
- CGRP-provoked headache is associated with a neuroimmune signature in idiopathic intracranial hypertension.The journal of headache and pain · 2026Trial
- Efficacy analysis of combined nerve combing and decompression for occipital neuralgia based on the classification of neurovascular relationships.Annals of medicine · 2026Article
- Integrated Identification of NAD⁺ Metabolism-Associated Candidate Genes.Molecular neurobiology · 2026Article
- Activation of NR2A-Wnt-TLR2 Signaling Axis in Satellite Glial Cells of the Dorsal Root Ganglion Contributes to Neuropathic Pain Induced by Nerve Injury in Diabetic Mice.Molecular neurobiology · 2025Article
- The interictal transcriptomic map of migraine without aura.The journal of headache and pain · 2025Article
- Neuroimmune interactions in the development and chronification of migraine headache.Trends in neurosciences · 2024Review
- Elevated cytokine levels in the central nervous system of cluster headache patients in bout and in remission.The journal of headache and pain · 2024Article
- Preoperative visualization of the greater occipital nerve with magnetic resonance imaging in candidates for occipital nerve decompression for headaches.Scientific reports · 2024Article
- Oxytocin Receptors on Calvarial Periosteal Innervation: Therapeutic Target for Post-Traumatic Headache?Pharmaceutics · 2024Article
- TLR2 Mediates Microglial Activation and Contributes to Central Sensitization in a Recurrent Nitroglycerin-induced Chronic Migraine Model.Molecular neurobiology · 2024Article
- The Dawn and Advancement of the Knowledge of the Genetics of Migraine.Journal of clinical medicine · 2024Review
- Deep and unbiased proteomics, pathway enrichment analysis, and protein-protein interaction of biomarker signatures in migraine.Therapeutic advances in chronic disease · 2024Article
- Functional outcomes between headache surgery and targeted botox injections: A prospective multicenter pilot study.JPRAS open · 2023Article
- Peripheral CCL2-CCR2 signalling contributes to chronic headache-related sensitization.Brain : a journal of neurology · 2023Article
- Debate: differences and similarities between tension-type headache and migraine.The journal of headache and pain · 2023Review
- Evidence of Chronic Complement Activation in Asymptomatic Pediatric Brain Injury Patients: A Pilot Study.Children (Basel, Switzerland) · 2022Article
- A population-health approach to characterizing migraine by comorbidity: Results from the Mindfulness and Migraine Cohort Study.Cephalalgia : an international journal of headache · 2022Article
- Toll-like receptors and their role in neuropathic pain and migraine.Molecular brain · 2022Review
- Increasing Collaboration between Headache Medicine and Plastic Surgery in the Surgical Management of Chronic Headache.Plastic and reconstructive surgery. Global open · 2022Article
- OnabotulinumtoxinA alters inflammatory gene expression and immune cells in chronic headache patients.Brain : a journal of neurology · 2022Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveChronic migraine (CM) is often associated with chronic tenderness of pericranial muscles. A distinct increase in muscle tenderness prior to onset of occipital headache that eventually progresses into a full-blown migraine attack is common. This experience raises the possibility that some CM attacks originate outside the cranium. The objective of this study was to determine whether there are extracranial pathophysiologies in these headaches.
methodsWe biopsied and measured the expression of gene transcripts (mRNA) encoding proteins that play roles in immune and inflammatory responses in affected (ie, where the head hurts) calvarial periosteum of (1) patients whose CMs are associated with muscle tenderness and (2) patients with no history of headache.
resultsExpression of proinflammatory genes (eg, CCL8, TLR2) in the calvarial periosteum significantly increased in CM patients attesting to muscle tenderness, whereas expression of genes that suppress inflammation and immune cell differentiation (eg, IL10RA, CSF1R) decreased.
interpretationBecause the upregulated genes were linked to activation of white blood cells, production of cytokines, and inhibition of NF-κB, and the downregulated genes were linked to prevention of macrophage activation and cell lysis, we suggest that the molecular environment surrounding periosteal pain fibers is inflamed and in turn activates trigeminovascular nociceptors that reach the affected periosteum through suture branches of intracranial meningeal nociceptors and/or somatic branches of the occipital nerve. This study provides the first set of evidence for localized extracranial pathophysiology in CM. Ann Neurol 2016;79:1000-1013.
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