ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
A sensory-labeled line for cold: TRPM8-expressing sensory neurons define the cellular basis for cold, cold pain, and cooling-mediated analgesia.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 166 papers, 4 of them syntheses that pooled it.
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Who cites it
166 citing papers in PubMed, 4 syntheses or guidelines pooled it, 267 citations in OpenAlex.
- Association between weather conditions and migraine: a systematic review and meta-analysis.Journal of neurology · 2025Pooled it
- Current Update on Categorization of Migraine Subtypes on the Basis of Genetic Variation: a Systematic Review.Molecular neurobiology · 2024Pooled it
- Mechanosensitive receptors in migraine: a systematic review.The journal of headache and pain · 2024Pooled it
- TRP Channels Interactome as a Novel Therapeutic Target in Breast Cancer.Frontiers in oncology · 2021Pooled it
- A novel TRPM8 agonist relieves dry eye discomfort.BMC ophthalmology · 2017Trial
- Experimenter-free pain assessment in mice using a thermal gradient ring and functional linear models.Pain reports · 2026Article
- Targeted cryostimulation of myofascial trigger points modulates exercise-induced physiological tremor in adolescent swimmers: a randomized counterbalanced crossover trial.BMC sports science, medicine & rehabilitation · 2026Article
- Somatosensory Functions of Melastatin Transient-Receptor Potential Channels in the Teeth: Molecular Basis for Thermal Dentine Hypersensitivity.Dentistry journal · 2026Review
- Article
- Dose and parameter specific effects of curcumin on neuropathic pain, cavity formation, and non-coding RNA expression in a spinal cord injury model.Scientific reports · 2026Article
- Skin pain in pediatric atopic dermatitis: mechanisms and management.Current opinion in allergy and clinical immunology · 2026Review
- Pharmacological Blockade of TRPM8 Ion Channels Fails to Reduce Behavioral and Biological Markers of Acute Oral Pain in Irradiated C57BL/6J Mice.Radiation research · 2026Article
- Suppression of neuropathic pain hypersensitivity by TRPM8 is mediated by mGluR group II and III receptors acting differentially on distinct nociceptor inputs to spinal cord.Frontiers in pharmacology · 2026Article
- Understanding animal temperature sensation: from molecular thermosensors to physiological impacts.Science China. Life sciences · 2026Review
- Transduction Mechanisms for Cold Temperature in Mouse Trigeminal and Vagal Ganglion Neurons Innervating Different Peripheral Organs.Acta physiologica (Oxford, England) · 2025Article
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- TRPM8 Protein Dynamics Correlates with Ligand Structure and Cellular Function.Journal of the American Chemical Society · 2025Article
- TRPM8 protein dynamics correlates with ligand structure and cellular function.bioRxiv : the preprint server for biology · 2025Article
- Transcriptomic Profile Analysis of Brain Tissue in the Absence of Functional TRPM8 Calcium Channel.Biomedicines · 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
106 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Many primary sensory neurons are polymodal, responding to multiple stimulus modalities (chemical, thermal, or mechanical), yet each modality is recognized differently. Although polymodality implies that stimulus encoding occurs in higher centers, such as the spinal cord or brain, recent sensory neuron ablation studies find that behavioral responses to different modalities require distinct subpopulations, suggesting the existence of modality-specific labeled lines at the level of the sensory afferent. Here we provide evidence that neurons expressing TRPM8, a cold- and menthol-gated channel required for normal cold responses in mammals, represents a labeled line solely for cold sensation. We examined the behavioral significance of conditionally ablating TRPM8-expressing neurons in adult mice, finding that, like animals lacking TRPM8 channels (Trpm8(-/-)), animals depleted of TRPM8 neurons ("ablated") are insensitive to cool to painfully cold temperatures. Ablated animals showed little aversion to noxious cold and did not distinguish between cold and a preferred warm temperature, a phenotype more profound than that of Trpm8(-/-) mice which exhibit only partial cold-avoidance and -preference behaviors. In addition to acute responses, cold pain associated with inflammation and nerve injury was significantly attenuated in ablated and Trpm8(-/-) mice. Moreover, cooling-induced analgesia after nerve injury was abolished in both genotypes. Last, heat, mechanical, and proprioceptive behaviors were normal in ablated mice, demonstrating that TRPM8 neurons are dispensable for other somatosensory modalities. Together, these data show that, although some limited cold sensitivity remains in Trpm8(-/-) mice, TRPM8 neurons are required for the breadth of behavioral responses evoked by cold temperatures.
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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.