ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Pharmacological blockade of the cold receptor TRPM8 attenuates autonomic and behavioral cold defenses and decreases deep body temperature.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers, 1 of them a synthesis that pooled it.
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Who cites it
119 citing papers in PubMed, 1 synthesis or guideline pooled it, 257 citations in OpenAlex.
- Menthol can be safely applied to improve thermal perception during physical exercise: a meta-analysis of randomized controlled trials.Scientific reports · 2020Pooled it
- L-Menthol attenuates the magnitude of cold-induced vasodilation on the extremities of young females.Journal of physiological anthropology · 2018Trial
- Effects of Thermal Stress on Growth and Reproduction ofAnimals : an open access journal from MDPI · 2026Review
- Cold- and TRPM8-dependent shaking in mammals and birds.Communications biology · 2025Article
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- Molecular mediators of cold adaptation in mammalian cells.Communications biology · 2025Review
- Skin transient receptor potential channels expression and microvascular reactivity to cooling in primary and secondary Raynaud's phenomenon.Physiological reports · 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
- Metal Ion Signaling in Biomedicine.Chemical reviews · 2025Review
- Huddling substates in mice facilitate dynamic changes in body temperature and are modulated by Shank3b and Trpm8 mutation.Communications biology · 2024Article
- Huddling substates in mice facilitate dynamic changes in body temperature and are modulated byResearch square · 2024Article
- Unveiling the Potential of Natural Compounds: A Comprehensive Review on Adipose Thermogenesis Modulation.International journal of molecular sciences · 2024Review
- Review
- Neural circuits of long-term thermoregulatory adaptations to cold temperatures and metabolic demands.Nature reviews. Neuroscience · 2024Review
- Allostasis in Neuroendocrine Systems Controlling Reproduction.Endocrinology · 2023Review
- Selection of preferred thermal environment and cold-avoidance responses in rats rely on signals transduced by the dorsal portion of the lateral funiculus of the spinal cord.Temperature (Austin, Tex.) · 2023Article
- Sex differences in thermoregulation in mammals: Implications for energy homeostasis.Frontiers in endocrinology · 2023Review
- Molecular determinants of TRPM8 function: key clues for a cool modulation.Frontiers in pharmacology · 2023Review
- How murine models of human disease and immunity are influenced by housing temperature and mild thermal stress.Temperature (Austin, Tex.) · 2023Review
- The neural pathway of the hyperthermic response to antagonists of the transient receptor potential vanilloid-1 channel.Temperature (Austin, Tex.) · 2023Article
59 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
We studied N-(2-aminoethyl)-N-(4-(benzyloxy)-3-methoxybenzyl)thiophene-2-carboxamide hydrochloride (M8-B), a selective and potent antagonist of the transient receptor potential melastatin-8 (TRPM8) channel. In vitro, M8-B blocked cold-induced and TRPM8-agonist-induced activation of rat, human, and murine TRPM8 channels, including those on primary sensory neurons. In vivo, M8-B decreased deep body temperature (T(b)) in Trpm8(+/+) mice and rats, but not in Trpm8(-/-) mice, thus suggesting an on-target action. Intravenous administration of M8-B was more effective in decreasing T(b) in rats than intrathecal or intracerebroventricular administration, indicating a peripheral action. M8-B attenuated cold-induced c-Fos expression in the lateral parabrachial nucleus, thus indicating a site of action within the cutaneous cooling neural pathway to thermoeffectors, presumably on sensory neurons. A low intravenous dose of M8-B did not affect T(b) at either a constantly high or a constantly low ambient temperature (T(a)), but the same dose readily decreased T(b) if rats were kept at a high T(a) during the M8-B infusion and transferred to a low T(a) immediately thereafter. These data suggest that both a successful delivery of M8-B to the skin (high cutaneous perfusion) and the activation of cutaneous TRPM8 channels (by cold) are required for the hypothermic action of M8-B. At tail-skin temperatures <23°C, the magnitude of the M8-B-induced decrease in T(b) was inversely related to skin temperature, thus suggesting that M8-B blocks thermal (cold) activation of TRPM8. M8-B affected all thermoeffectors studied (thermopreferendum, tail-skin vasoconstriction, and brown fat thermogenesis), thus suggesting that TRPM8 is a universal cold receptor in the thermoregulation system.
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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.