ArticleBritish journal of pharmacology2016
Meningeal blood flow is controlled by H2 S-NO crosstalk activating a HNO-TRPA1-CGRP signalling pathway.
Article in British journal of pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 57 citations in OpenAlex.
- A delayed endothelial-glial mechanism for CGRP-induced migraine.The journal of headache and pain · 2026Review
- Pretreatment with an anti-CGRP monoclonal antibody attenuates mild TBI-induced tactile hypersensitivity in mice.The journal of headache and pain · 2025Article
- Transient Receptor Potential Ankyrin 1 (TRPA1) Mediates Hydrogen Sulfide-induced CaCurrent neuropharmacology · 2025Article
- Article
- Endothelial-dependent relaxation of α-pinene and two metabolites, myrtenol and verbenol, in isolated murine blood vessels.American journal of physiology. Heart and circulatory physiology · 2023Article
- Micromotion Derived Fluid Shear Stress Mediates Peri-Electrode Gliosis through Mechanosensitive Ion Channels.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Meningeal Mechanisms and the Migraine Connection.Annual review of neuroscience · 2023Review
- CGRP physiology, pharmacology, and therapeutic targets: migraine and beyond.Physiological reviews · 2023Review
- Potential Effects of Natural HBiomolecules · 2022Review
- Nitroxyl Delivered by Angeli's Salt Causes Short-Lasting Activation Followed by Long-Lasting Deactivation of Meningeal Afferents in Models of Headache Generation.International journal of molecular sciences · 2022Article
- CGRP measurements in human plasma - a methodological study.Cephalalgia : an international journal of headache · 2021Article
- The Potential Role of Hydrogen Sulfide in the Regulation of Cerebrovascular Tone.Biomolecules · 2020Review
- Cross-talk signaling in the trigeminal ganglion: role of neuropeptides and other mediators.Journal of neural transmission (Vienna, Austria : 1996) · 2020Review
- TRP Channels in the Focus of Trigeminal Nociceptor Sensitization Contributing to Primary Headaches.International journal of molecular sciences · 2020Review
- Current understanding of trigeminal ganglion structure and function in headache.Cephalalgia : an international journal of headache · 2019Review
- TRP Channels and Migraine: Recent Developments and New Therapeutic Opportunities.Pharmaceuticals (Basel, Switzerland) · 2019Review
- Effects of sulfide and polysulfides transmitted by direct or signal transduction-mediated activation of TRPA1 channels.British journal of pharmacology · 2019Review
- A Chemiluminescent Probe for HNO Quantification and Real-Time Monitoring in Living Cells.Angewandte Chemie (International ed. in English) · 2019Article
- Induction of chronic migraine phenotypes in a rat model after environmental irritant exposure.Pain · 2018Article
- Chemical Biology of HChemical reviews · 2018Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeMeningeal blood flow is controlled by CGRP released from trigeminal afferents and NO mainly produced in arterial endothelium. The vasodilator effect of NO may be due to the NO-derived compound, nitroxyl (HNO), generated through reaction with endogenous H2 S. We investigated the involvement of HNO in CGRP release and meningeal blood flow. EXPERIMENTAL APPROACH: Blood flow in exposed dura mater of rats was recorded by laser Doppler flowmetry. CGRP release from the dura mater in the hemisected rat head was quantified using an elisa. NO and H2 S were localized histochemically with specific sensors. KEY
resultsTopical administration of the NO donor diethylamine-NONOate increased meningeal blood flow by 30%. Pretreatment with oxamic acid, an inhibitor of H2 S synthesis, reduced this effect. Administration of Na2 S increased blood flow by 20%, an effect abolished by the CGRP receptor antagonist CGRP8-37 or the TRPA1 channel antagonist HC030031 and reduced when endogenous NO synthesis was blocked. Na2 S dose-dependently increased CGRP release two- to threefold. Co-administration of diethylamine-NONOate facilitated CGRP release, while inhibition of endogenous NO or H2 S synthesis lowered basal CGRP release. NO and H2 S were mainly localized in arterial vessels, HNO additionally in nerve fibre bundles. HNO staining was lost after treatment with L-NMMA and oxamic acid. CONCLUSIONS AND IMPLICATIONS: NO and H2 S cooperatively increased meningeal blood flow by forming HNO, which activated TRPA1 cation channels in trigeminal fibres, inducing CGRP release. This HNO-TRPA1-CGRP signalling pathway may be relevant to the pathophysiology of headaches.
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