ArticleFrontiers in molecular neuroscience2021
Transient Receptor Potential Channel 4 Small-Molecule Inhibition Alleviates Migraine-Like Behavior in Mice.
Article in Frontiers in molecular neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- Mechanosensitive receptors in migraine: a systematic review.The journal of headache and pain · 2024Pooled it
- Autoantibodies in small fiber neuropathy: frequency and clinical features associated with antibodies to the novel targets MX1 and DBNL.Journal of neurology · 2026Observational
- TRPC4/TRPC5 are critical for neuronal modulation by transcranial focused ultrasound in retrosplenial cortex in male mice.Nature communications · 2026Article
- Genome-wide association analysis of treatment response to onabotulinumtoxinA in Han Chinese patients with chronic migraine: a pilot study.BMC neurology · 2026Article
- TRPC Channels as Mediators of Hypoxia-Induced Pulmonary Hypertension in Obstructive Sleep Apnea.International journal of molecular sciences · 2026Review
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- TRPC4 Mediates Trigeminal Neuropathic Pain via CaCNS neuroscience & therapeutics · 2025Article
- Targeting Nociceptive Neurons and Transient Receptor Potential Channels for the Treatment of Migraine.International journal of molecular sciences · 2023Review
- CGRP physiology, pharmacology, and therapeutic targets: migraine and beyond.Physiological reviews · 2023Review
- Unpredictable Sound Stress Model Causes Migraine-Like Behaviors in Mice With Sexual Dimorphism.Frontiers in pharmacology · 2022Article
- Sex differences in the expression of calcitonin gene-related peptide (CGRP) and its receptor: a review of contradictory and nuanced findings.Neurobiology of pain (Cambridge, Mass.)Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Migraine is a common neurological disorder with few available treatment options. Recently, we have demonstrated the role of transient receptor potential cation channel subfamily C member 4 (TRPC4) in itch and the modulation of the calcitonin gene-related peptide (CGRP), a biomarker and emerging therapeutic target for migraine. In this study, we characterized the role of TRPC4 in pain and evaluated its inhibition as anti-migraine pain therapy in preclinical mouse models. First, we found that TRPC4 is highly expressed in trigeminal ganglia and its activation not only mediates itch but also pain. Second, we demonstrated that the small-molecule inhibitor ML204, a specific TRPC4 antagonist, significantly reduced episodic and chronic migraine-like behaviors in male and female mice after injection of nitroglycerin (NTG), a well-known migraine inducer in rodents and humans. Third, we found a significant decrease in CGRP protein levels in the plasma of both male and female mice treated with ML-204, which largely prevented the development of chronic migraine-like behavior. Using sensory neuron cultures, we confirmed that activation of TRPC4 elicited release of CGRP, which was significantly diminished by ML-204. Collectively, our findings identify TRPC4 in peripheral sensory neurons as a mediator of CGRP release and NTG-evoked migraine. Since a TRPC4 antagonist is already in clinical trials, we expect that this study will rapidly lead to novel and effective clinical treatments for migraineurs.
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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.