ArticlePain2013
TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain.
Article in Pain, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 172 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
172 citing papers in PubMed, 3 syntheses or guidelines pooled it, 308 citations in OpenAlex.
- Systematic Review and Meta-Analysis: Plant-Based Therapy for Irritable Bowel Syndrome.Phytotherapy research : PTR · 2026Pooled it
- Association between weather conditions and migraine: a systematic review and meta-analysis.Journal of neurology · 2025Pooled it
- Systematic Review on Herbal Preparations for Controlling Visceral Hypersensitivity in Functional Gastrointestinal Disorders.Current pharmaceutical biotechnology · 2024Pooled it
- A multicenter, randomized, double-blind, double-simulated, positive drug parallel-controlled clinical trial to evaluate the efficacy and safety of Xiao'er Fengreqing oral liquid in the treatment of acute pharyngitis/tonsillitis in children.Frontiers in pharmacology · 2026Trial
- Skin cooling and topical application of menthol can reduce propofol injection-induced pain, a randomized trial.Medicine · 2025Trial
- Acute analgesic effect of nicotine vaping using three experimental pain induction tasks: a randomized, placebo-controlled laboratory study.Psychopharmacology · 2025Trial
- Menthol alleviates post-race elevations in muscle soreness and metabolic and respiratory stress during running.European journal of applied physiology · 2024Trial
- Evaluation of the Effectiveness of Iontophoresis with Perskindol Gel in Patients with Osteoarthritis of the Knee Joints.International journal of environmental research and public health · 2022Trial
- A novel duodenal-release formulation of caraway oil and L-menthol is a safe, effective and well tolerated therapy for functional dyspepsia.BMC gastroenterology · 2022Trial
- Menthol-induced activation of TRPM8 receptors increases cutaneous blood flow across the dermatome.Microvascular research · 2022Trial
- A Novel, Duodenal-Release Formulation of a Combination of Caraway Oil and L-Menthol for the Treatment of Functional Dyspepsia: A Randomized Controlled Trial.Clinical and translational gastroenterology · 2019Trial
- Acute effects of inhaled menthol on the rewarding effects of intravenous nicotine in smokers.Journal of psychopharmacology (Oxford, England) · 2018Trial
- A clinical and mechanistic study of topical borneol-induced analgesia.EMBO molecular medicine · 2017Trial
- Topical menthol increases cutaneous blood flow.Microvascular research · 2016Trial
- Preparing and evaluating the effectiveness of topical cerosome of menthol on radial spasm and pain in patients with trans-radial angiography: a randomized, triple-blind, parallel placebo-controlled clinical trial.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Molecular basis for cold and menthol sensing by mammalian TRPM8.Nature communications · 2026Article
- Symmetry-driven gating of TRPM8 by PIPNature communications · 2026Article
- Article
- Topical Pain Management: An Updated Review of Current Evidence and Emerging Strategies.Journal of clinical medicine · 2026Review
- Preflavour and postflavour ban oral nicotine pouches: a chemical, sensory and young adult appeal analysis.Tobacco control · 2026Article
112 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Menthol, the cooling natural product of peppermint, is widely used in medicinal preparations for the relief of acute and inflammatory pain in sports injuries, arthritis, and other painful conditions. Menthol induces the sensation of cooling by activating TRPM8, an ion channel in cold-sensitive peripheral sensory neurons. Recent studies identified additional targets of menthol, including the irritant receptor, TRPA1, voltage-gated ion channels and neurotransmitter receptors. It remains unclear which of these targets contribute to menthol-induced analgesia, or to the irritating side effects associated with menthol therapy. Here, we use genetic and pharmacological approaches in mice to probe the role of TRPM8 in analgesia induced by L-menthol, the predominant analgesic menthol isomer in medicinal preparations. L-menthol effectively diminished pain behavior elicited by chemical stimuli (capsaicin, acrolein, acetic acid), noxious heat, and inflammation (complete Freund's adjuvant). Genetic deletion of TRPM8 completely abolished analgesia by L-menthol in all these models, although other analgesics (acetaminophen) remained effective. Loss of L-menthol-induced analgesia was recapitulated in mice treated with a selective TRPM8 inhibitor, AMG2850. Selective activation of TRPM8 with WS-12, a menthol derivative that we characterized as a specific TRPM8 agonist in cultured sensory neurons and in vivo, also induced TRPM8-dependent analgesia of acute and inflammatory pain. L-menthol- and WS-12-induced analgesia was blocked by naloxone, suggesting activation of endogenous opioid-dependent analgesic pathways. Our data show that TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain. In contrast to menthol, selective TRPM8 agonists may produce analgesia more effectively, with diminished side effects.
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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.