ArticleNature communications2019
Maladaptive activation of Nav1.9 channels by nitric oxide causes triptan-induced medication overuse headache.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- Electrophysiological Properties and Mechanical Sensitivity of Trigeminal Ganglionic Neurons That Innervate the Maxillary Sinus in Mice.International journal of molecular sciences · 2026Article
- Stromal Cell-Mast Cell Communication Orchestrates Anti-Viral Immunity in the Meninges.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- 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
- Induction of more severe central sensitization in a medication overuse headache model mice through active ingestion of rizatriptan.The journal of headache and pain · 2025Article
- Pregnenolone sulfate potentiates tetrodotoxin-resistant NaThe journal of headache and pain · 2025Article
- Mepyramine targets mutant Nav1.7 channels to relieve pain and erythema in primary erythromelalgia patients.Frontiers in medicine · 2025Article
- Article
- CGRP physiology, pharmacology, and therapeutic targets: migraine and beyond.Physiological reviews · 2023Review
- Activation of the microglial P2X7R/NLRP3 inflammasome mediates central sensitization in a mouse model of medication overuse headache.Frontiers in molecular neuroscience · 2023Article
- A compendium of validated pain genes.WIREs mechanisms of disease · 2022Review
- NaJournal of neurophysiology · 2022Article
- Contribution of tetrodotoxin-resistant persistent NaThe journal of headache and pain · 2022Article
- A prolactin-dependent sexually dimorphic mechanism of migraine chronification.Cephalalgia : an international journal of headache · 2022Article
- Xiongshao Zhitong Recipe Attenuates Nitroglycerin-Induced Migraine-Like BehaviorsFrontiers in pharmacology · 2022Article
- Calmodulin Interactions with Voltage-Gated Sodium Channels.International journal of molecular sciences · 2021Review
- Article
- Involvement of Mast Cells in the Pathophysiology of Pain.Frontiers in cellular neuroscience · 2021Article
- Differential medication overuse risk of novel anti-migraine therapeutics.Brain : a journal of neurology · 2020Article
- Modulation of the lifespan ofChemical science · 2020Article
- Spider venom-derived peptide induces hyperalgesia in NaNature communications · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Medication-overuse headaches (MOH) occur with both over-the-counter and pain-relief medicines, including paracetamol, opioids and combination analgesics. The mechanisms that lead to MOH are still uncertain. Here, we show that abnormal activation of Nav1.9 channels by Nitric Oxide (NO) is responsible for MOH induced by triptan migraine medicine. Deletion of the Scn11a gene in MOH mice abrogates NO-mediated symptoms, including cephalic and extracephalic allodynia, photophobia and phonophobia. NO strongly activates Nav1.9 in dural afferent neurons from MOH but not normal mice. Abnormal activation of Nav1.9 triggers CGRP secretion, causing artery dilatation and degranulation of mast cells. In turn, released mast cell mediators potentiates Nav1.9 in meningeal nociceptors, exacerbating inflammation and pain signal. Analysis of signaling networks indicates that PKA is downregulated in trigeminal neurons from MOH mice, relieving its inhibitory action on NO-Nav1.9 coupling. Thus, anomalous activation of Nav1.9 channels by NO, as a result of chronic medication, promotes MOH.
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