ArticleScientific reports2019
Reduced TRPM8 expression underpins reduced migraine risk and attenuated cold pain sensation in humans.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Deciphering the Role of the rs2651899, rs10166942, and rs11172113 Polymorphisms in Migraine: A Meta-Analysis.Medicina (Kaunas, Lithuania) · 2022Pooled it
- Effect of ambient cold exposure on pain modulation: exploring individually reported thermal comfort as moderating factor in a crossover study of young adults.Scandinavian journal of pain · 2026Trial
- Article
- Temperature-Dependent Menthol Binding across TRPM8 Conformational States.Journal of the American Chemical Society · 2026Article
- Deep mutational scan of the pore of the cold-sensing TRPM8 channel.bioRxiv : the preprint server for biology · 2026Article
- TRPtracker: a community database for monitoring praziquantel sensitivity at TRPMInternational journal for parasitology. Drugs and drug resistance · 2026Article
- The therapeutic pipeline in migraine: What does the future hold?Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Tooth Pulp Afferents and Transient Receptor Potential (TRP) Ion Channels as Key Regulators of Pulp Homeostasis, Inflammation, and Pain.International journal of molecular sciences · 2025Review
- Buried Treasure? Overlooked and Newly Discovered Evolutionary Contributions to Human Brain Diseases.Annals of neurology · 2025Review
- TRPtracker: a community database for monitoring praziquantel sensitivity at TRPMbioRxiv : the preprint server for biology · 2025Article
- Unveiling migraine subtype heterogeneity and risk loci: integrated genome-wide association study and single-cell transcriptomics discovery.The journal of headache and pain · 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
- TRPM8 Mutations Associated With Persistent Pain After Surgical Injury of Corneal Trigeminal Axons.Neurology. Genetics · 2024Article
- The neurotrophic factor artemin and its receptor GFRα3 mediate migraine-like pain via the ion channel TRPM8.Cephalalgia : an international journal of headache · 2024Article
- The neurotrophic factor artemin and its receptor GFRα3 mediate migraine-like pain via the ion channel TRPM8.bioRxiv : the preprint server for biology · 2024Article
- Article
- Do Individual Differences in Perception Affect Awareness of Climate Change?Brain sciences · 2024Article
- Targeting Nociceptive Neurons and Transient Receptor Potential Channels for the Treatment of Migraine.International journal of molecular sciences · 2023Review
- Novel Therapeutic Targets for Migraine.Biomedicines · 2023Review
- Association between TRP channels and glutamatergic synapse gene polymorphisms and migraine and the comorbidities anxiety and depression in a Chinese population.Frontiers in genetics · 2023Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple genome-wide association studies have identified non-coding single-nucleotide variants (SNVs) near (e.g., rs10166942[C]) or within (rs17862920[T]) the TRPM8 gene that encodes a cold thermosensor is associated with reduced migraine risk. Furthermore, rs10166942[C]) and rs10166942[T]) are more prevalent in populations that reside in hotter and colder climates, respectively. Here we assessed whether these alleles affect TRPM8 expression in humans and human physiologic responses to cold challenge. Here we show that TRPM8 expression is decreased from the chromosome harboring the rs10166942[C] allele in the human dorsal root ganglia. Moreover, carriers of rs10166942[C] required significantly lower temperatures and longer duration of exposure to reach a cold pain threshold (CPTh), which correlated with decreased TRPM8 expression expected in the carriers. This study provides evidence for a genotype-dependent influence on cold pain sensation suggesting that carriers of the reduced migraine risk allele have reduced sensitivity to cold stimuli and that TRPM8 acts as a cold thermosensor and cold pain transducer in humans. Reduced TRPM8 expression and function underpins the migraine protection in carriers of rs10166942[C]; thus, the evaluation of TRPM8 antagonists as migraine therapeutics is warranted. Furthermore, these results provide mechanistic insights for evolutionary positive selection of rs10166942[T] allele in adaptation along latitudinal cline to colder climates.
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