ArticleCephalalgia : an international journal of headache2018
Functional interactions between transient receptor potential M8 and transient receptor potential V1 in the trigeminal system: Relevance to migraine pathophysiology.
Article in Cephalalgia : an international journal of headache, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 49 citations in OpenAlex.
- The therapeutic pipeline in migraine: What does the future hold?Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Transient Receptor Potential Channels as Key Regulators of Neuroinflammation in Neurological Disorders: Mechanistic Insights, Therapeutic Potentials, and Future Directions.CNS neuroscience & therapeutics · 2025Review
- Evaluation of the Effects of Eye Drops for Dry Eyes on Neuronal Pain Receptors in a Primary Culture Model of Trigeminal Ganglion Cells.Journal of clinical medicine · 2025Article
- Activation of central and peripheral transient receptor potential melastatin 8 increases susceptibility to spreading depolarization and facilitates trigeminal neuroinflammation.The journal of headache and pain · 2025Article
- Epigenetic Connections of the TRPA1 Ion Channel in Pain Transmission and Neurogenic Inflammation - a Therapeutic Perspective in Migraine?Molecular neurobiology · 2023Review
- Targeting Nociceptive Neurons and Transient Receptor Potential Channels for the Treatment of Migraine.International journal of molecular sciences · 2023Review
- TRP Channels: Recent Development in Translational Research and Potential Therapeutic Targets in Migraine.International journal of molecular sciences · 2022Review
- Sustained Effects of CGRP Blockade on Cortical Spreading Depolarization-Induced Alterations in Facial Heat Pain Threshold, Light Aversiveness, and Locomotive Activity in the Light Environment.International journal of molecular sciences · 2022Article
- TRPM8 contributes to sex dimorphism by promoting recovery of normal sensitivity in a mouse model of chronic migraine.Nature communications · 2022Article
- Role of Omics in Migraine Research and Management: A Narrative Review.Molecular neurobiology · 2022Review
- Different Involvement of ASIC and TRPA1 in Facial and Hindpaw Allodynia in Nitroglycerin-Induced Peripheral Hypersensitivities in Mice.Life (Basel, Switzerland) · 2022Article
- PACAP-38 Induces Transcriptomic Changes in Rat Trigeminal Ganglion Cells Related to Neuroinflammation and Altered Mitochondrial Function Presumably via PAC1/VPAC2 Receptor-Independent Mechanism.International journal of molecular sciences · 2022Article
- The distinctive role of menthol in pain and analgesia: Mechanisms, practices, and advances.Frontiers in molecular neuroscience · 2022Review
- TRPM8 Channels: Advances in Structural Studies and Pharmacological Modulation.International journal of molecular sciences · 2021Review
- Implications of Transient Receptor Potential Cation Channels in Migraine Pathophysiology.Neuroscience bulletin · 2021Review
- Highly functionalized β-lactams and 2-ketopiperazines as TRPM8 antagonists with antiallodynic activity.Scientific reports · 2020Article
- Cortical spreading depolarisation-induced facial hyperalgesia, photophobia and hypomotility are ameliorated by sumatriptan and olcegepant.Scientific reports · 2020Article
- 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
- Prophylactic Electroacupuncture on the Upper Cervical Segments Decreases Neuronal Discharges of the Trigeminocervical Complex in Migraine-Affected Rats: An in vivo Extracellular Electrophysiological Experiment.Journal of pain research · 2020Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background Recent genome-wide association studies have identified transient receptor potential M8 ( TRPM8) as a migraine susceptibility gene. TRPM8 is a nonselective cation channel that mediates cool perception. However, its precise role in migraine pathophysiology is elusive. Transient receptor potential V1 (TRPV1) is a nonselective cation channel activated by noxious heat. Both TRPM8 and TRPV1 are expressed in trigeminal ganglion (TG) neurons. Methods We investigated the functional roles of TRPM8 and TRPV1 in a meningeal inflammation-based migraine model by measuring the effects of facial TRPM8 activation on thermal allodynia and assessing receptor coexpression changes in TG neurons. We performed retrograde tracer labeling to identify TG neurons innervating the face and dura. Results We found that pharmacological TRPM8 activation reversed the meningeal inflammation-induced lowering of the facial heat pain threshold, an effect abolished by genetic ablation of TRPM8. No significant changes in the heat pain threshold were seen in sham-operated animals. Meningeal inflammation caused dynamic alterations in TRPM8/TRPV1 coexpression patterns in TG neurons, and colocalization was most pronounced when the ameliorating effect of TRPM8 activation on thermal allodynia was maximal. Our tracer assay disclosed the presence of dura-innervating TG neurons sending collaterals to the face. Approximately half of them were TRPV1-positive. We also demonstrated functional inhibition of TRPV1 by TRPM8 in a cell-based assay using c-Jun N-terminal kinase phosphorylation as a surrogate marker. Conclusions Our findings provide a plausible mechanism to explain how facial TRPM8 activation can relieve migraine by suppressing TRPV1 activity. Facial TRPM8 appears to be a promising therapeutic target for migraine.
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