ArticleTobacco control2016
Menthol decreases oral nicotine aversion in C57BL/6 mice through a TRPM8-dependent mechanism.
Article in Tobacco control, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
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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.
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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
50 citing papers in PubMed, 64 citations in OpenAlex.
- Synthetic cooling agents enhance nicotine reinforcement and mesolimbic dopamine signaling.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Influence of Cooling Agents on the Arrhythmogenic and Autonomic Effects of Electronic Cigarettes in an in vivo Model.Circulation. Arrhythmia and electrophysiology · 2026Article
- Evaluation of molecular interactions of vaping juice components with ACE2 receptor.Scientific reports · 2026Article
- Influence of e-cigarettes and their constituents on cardiac rhythm and arrhythmias.American journal of physiology. Heart and circulatory physiology · 2026Review
- Artificial Sweeteners in US-Marketed Oral Nicotine Pouch Products: Correlation With Nicotine Contents and Effects on Product Preference.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2026Article
- Coolants, organic acids, flavourings and other additives that facilitate inhalation of tobacco and nicotine products: implications for regulation.Tobacco control · 2026Review
- Modulation of monoaminergic neurotransmission in substance use disorders: a neuropharmacological perspective focusing on plant-derived metabolites.Frontiers in pharmacology · 2026Review
- Differences in "minty" flavor compound and synthetic cooling agent presence in US-marketed menthol-mint e-liquids and devices between 2019-2023.Research square · 2025Article
- Cardiovascular Health Effects and Synthetic Cooling Agents in E-Cigarettes Labeled as "Clear" Marketed in Massachusetts After the Tobacco Product Flavoring Ban.Journal of the American Heart Association · 2025Article
- MMP12 deficiency attenuates menthol e-cigarette plus house dust-mite effects on pulmonary iron homeostasis and oxidative stress.Respiratory research · 2025Article
- 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
- The Impact of High or Low Doses of Nicotine in a Mouse Model of Vapor Self-Administration.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2024Article
- Artificial Sweeteners in US-Marketed Oral Nicotine Pouch Products: Correlation with Nicotine Contents and Effects on Product Preference.bioRxiv : the preprint server for biology · 2024Article
- Reduced menthol sensitivity in a prodromal Parkinson's disease model induced by intranasal rotenone treatment.Frontiers in cellular neuroscience · 2024Article
- Ice flavours and non-menthol synthetic cooling agents in e-cigarette products: a review.Tobacco control · 2023Review
- Characterizing different-flavored e-cigarette solutions from user-reported sensory attributes and appeal.Experimental and clinical psychopharmacology · 2023Article
- Synthetic Cooling Agents in US-marketed E-cigarette Refill Liquids and Popular Disposable E-cigarettes: Chemical Analysis and Risk Assessment.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2022Article
- Evaluation of Flavor Effects on Oral Nicotine Liking and/or Disliking Using the Taste Reactivity Test in Rats.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2022Article
- Animal Models to Investigate the Impact of Flavors on Nicotine Addiction and Dependence.Current neuropharmacology · 2022Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundNicotine is a major oral irritant in smokeless tobacco products and has an aversive taste. Mentholated smokeless tobacco products are highly popular, suggesting that menthol increases their palatability and may facilitate initiation of product use. While menthol is known to reduce respiratory irritation by tobacco smoke irritants, it is not known whether this activity extends to oral nicotine and its aversive effects. STUDY
designThe two-bottle choice drinking assay was used to characterise aversion and preference in C57BL/6 mice to a range of menthol concentrations (10-200 µg/mL). Then, effects of menthol on oral nicotine aversion were determined. Responses were compared with those in mice deficient in the cold/menthol receptor, TRPM8, expressed in trigeminal sensory neurons innervating the oral cavity.
resultsMice showed aversion to menthol concentrations of 100 µg/mL and above. When presented with a highly aversive concentration of nicotine (200 µg/mL), mice preferred solutions with 50 or 100 µg/mL menthol added over nicotine alone. In contrast to wild-type mice, Trpm8-/- showed a strong aversion to mentholated (100 µg/mL) nicotine (200 µg/mL) and preferred nicotine alone. Trpm8-/- mice show aversion to lower concentrations of menthol than wild-type mice.
conclusionsOral menthol can reduce the aversive effects of oral nicotine and, at higher concentrations, acts as an irritant by itself. Menthol's effects in relation to nicotine require TRPM8, the cool temperature sensing ion channel that activates analgesic and counterirritant mechanisms. These mechanisms may underlie preference for menthol-containing smokeless tobacco products and may facilitate initiation of product use.
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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.