ArticleInternational journal of molecular sciences2022
Testing the Role of Glutamate NMDA Receptors in Peripheral Trigeminal Nociception Implicated in Migraine Pain.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- TRPV1‑mediated central sensitisation: Core mechanisms of migraine chronification and novel targeted therapeutic strategies (Review).International journal of molecular medicine · 2026Review
- Peripheral nervous system involvement accompanies central nervous system involvement in anti-N-methyl-D-aspartate receptor encephalitis.Frontiers in immunology · 2026Article
- Mapping the brain cell-specific regulatory architecture of migraine: a single-cell causal framework nominating inhibitory-neuronal BTBD16 and astrocytic RIMS1 as therapeutic targets.The journal of headache and pain · 2025Article
- Exploring the Analgesic Potential of L-Lysine: Molecular Mechanisms, Preclinical Evidence, and Implications for Pharmaceutical Pain Therapy.Pharmaceutics · 2025Review
- Unmasking the relationship between CGRP and glutamate: from peripheral excitation to central sensitization in migraine.The journal of headache and pain · 2025Review
- Glutamate as a Therapeutic Substrate in Migraine.International journal of molecular sciences · 2025Review
- The Role of Purinergic Mechanisms in the Excitability of Trigeminal Afferents of Rats with Prenatal Hyperhomocysteinemia.Biomolecules · 2025Article
- Sex difference in TRPM3 channel functioning in nociceptive and vascular systems: an emerging target for migraine therapy in females?The journal of headache and pain · 2025Review
- The Potential Role of Glutamate Receptors and their Antagonists or Modulators in Migraine Therapy.Current neuropharmacology · 2025Review
- Harnessing Miniscope Imaging in Freely Moving Animals to Unveil Migraine Pathophysiology and Validate Novel Therapeutic Strategies.Synapse (New York, N.Y.) · 2024Review
- Chronic Hyperhomocysteinemia Impairs CSD Propagation and Induces Cortical Damage in a Rat Model of Migraine with Aura.Biomolecules · 2024Article
- Magnesium for disease treatment and prevention: emerging mechanisms and opportunities.Trends in pharmacological sciences · 2024Review
- Whole Body Cryostimulation: A New Adjuvant Treatment in Central Sensitization Syndromes? An Expert Opinion.Healthcare (Basel, Switzerland) · 2024Article
- Targeting Glutamate Neurotoxicity through Dietary Manipulation: Potential Treatment for Migraine.Nutrients · 2023Review
- Glia Signaling and Brain Microenvironment in Migraine.Molecular neurobiology · 2023Review
- Molecular Research on Migraine: From Pathogenesis to Treatment.International journal of molecular sciences · 2023Article
- Effects of Nitric Oxide on the Activity of P2X and TRPV1 Receptors in Rat Meningeal Afferents of the Trigeminal Nerve.International journal of molecular sciences · 2023Article
- The Interactions of Magnesium Sulfate and Cromoglycate in a Rat Model of Orofacial Pain; The Role of Magnesium on Mast Cell Degranulation in Neuroinflammation.International journal of molecular sciences · 2023Article
- Targeting Peripheral N-Methyl-D-Aspartate Receptor (NMDAR): A Novel Strategy for the Treatment of Migraine.Journal of clinical medicine · 2023Review
- Arc-Mediated Synaptic Plasticity Regulates Cognitive Function in a Migraine Mouse Model.Brain sciences · 2023Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The pro-nociceptive role of glutamate in the CNS in migraine pathophysiology is well established. Glutamate, released from trigeminal afferents, activates second order nociceptive neurons in the brainstem. However, the function of peripheral glutamate receptors in the trigeminovascular system suggested as the origin site for migraine pain, is less known. In the current project, we used calcium imaging and patch clamp recordings from trigeminal ganglion (TG) neurons, immunolabelling, CGRP assay and direct electrophysiological recordings from rat meningeal afferents to investigate the role of glutamate in trigeminal nociception. Glutamate, aspartate, and, to a lesser extent, NMDA under free-magnesium conditions, evoked calcium transients in a fraction of isolated TG neurons, indicating functional expression of NMDA receptors. The fraction of NMDA sensitive neurons was increased by the migraine mediator CGRP. NMDA also activated slowly desensitizing currents in 37% of TG neurons. However, neither glutamate nor NMDA changed the level of extracellular CGRP. TG neurons expressed both GluN2A and GluN2B subunits of NMDA receptors. In addition, after removal of magnesium, NMDA activated persistent spiking activity in a fraction of trigeminal nerve fibers in meninges. Thus, glutamate activates NMDA receptors in somas of TG neurons and their meningeal nerve terminals in magnesium-dependent manner. These findings suggest that peripherally released glutamate can promote excitation of meningeal afferents implicated in generation of migraine pain in conditions of inherited or acquired reduced magnesium blockage of NMDA channels and support the usage of magnesium supplements in migraine.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.