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Journal of Neuroinflammation Jul 2022No reports exist as to neuroprotective effects associated with topical activation of transient receptor potential melastatin 8 (TRPM8), a noted cold receptor. In the...
BACKGROUND
No reports exist as to neuroprotective effects associated with topical activation of transient receptor potential melastatin 8 (TRPM8), a noted cold receptor. In the present study, we identified whether activating peripheral TRPM8 can be an adjuvant therapy for ischemic stroke.
METHODS
Menthol, an agonist of TRPM8, was applied orally or topically to all paws or back of the mouse after middle cerebral artery occlusion (MCAO). We used Trpm8 gene knockout (Trpm8) mice or TRPM8 antagonist and lidocaine to validate the roles of TRPM8 and peripheral nerve conduction in menthol against ischemic stroke.
RESULTS
Application of menthol 16% to paw derma attenuated infarct volumes and ameliorated sensorimotor deficits in stroke mice induced by MCAO. The benefits of topically applied menthol were associated with reductions in oxidative stress, neuroinflammation and infiltration of monocytes and macrophages in ischemic brains. Antagonizing TRPM8 or Trpm8 knockout dulls the neuroprotective effects of topically application of menthol against MCAO. Immunohistochemistry analyses revealed significantly higher TRPM8 expression in skin tissue samples obtained from the paws compared with skin from the backs, which was reflected by significantly smaller infarct lesion volumes and better sensorimotor function in mice treated with menthol on the paws compared with the back. Blocking conduction of peripheral nerve in the four paws reversed the neuroprotective effects of topical menthol administrated to paws. On the other hand, oral menthol dosing did not assist with recovery from MCAO in our study.
CONCLUSION
Our results suggested that activation of peripheral TRPM8 expressed in the derma tissue of limbs with sufficient concentration of menthol is beneficial to stroke recovery. Topical application of menthol on hands and feet could be a novel and simple-to-use therapeutic strategy for stroke patients.
Topics: Animals; Infarction; Ischemic Stroke; Menthol; Mice; Neuroprotective Agents; TRPM Cation Channels
PubMed: 35897101
DOI: 10.1186/s12974-022-02553-4 -
Journal of Neurophysiology Feb 2022Unmyelinated tactile (C-tactile or CT) afferents are abundant in arm hairy skin and have been suggested to signal features of social affective touch. Here, we recorded...
Unmyelinated tactile (C-tactile or CT) afferents are abundant in arm hairy skin and have been suggested to signal features of social affective touch. Here, we recorded from unmyelinated low-threshold mechanosensitive afferents in the peroneal and radial nerves. The most distal receptive fields were located on the proximal phalanx of the third finger for the superficial branch of the radial nerve and near the lateral malleolus for the peroneal nerve. We found that the physiological properties with regard to conduction velocity and mechanical threshold, as well as their tuning to brush velocity, were similar in CT units across the antebrachial ( = 27), radial ( = 8), and peroneal ( = 4) nerves. Moreover, we found that although CT afferents are readily found during microneurography of the arm nerves, they appear to be much more sparse in the lower leg compared with C-nociceptors. We continued to explore CT afferents with regard to their chemical sensitivity and found that they could not be activated by topical application to their receptive field of either the cooling agent menthol or the pruritogen histamine. In light of previous studies showing the combined effects that temperature and mechanical stimuli have on these neurons, these findings add to the growing body of research suggesting that CT afferents constitute a unique class of sensory afferents with highly specialized mechanisms for transducing gentle touch. Unmyelinated tactile (CT) afferents are abundant in arm hairy skin and are thought to signal features of social affective touch. We show that CTs are also present but are relatively sparse in the lower leg compared with C-nociceptors. CTs display similar physiological properties across the arm and leg nerves. Furthermore, CT afferents do not respond to the cooling agent menthol or the pruritogen histamine, and their mechanical response properties are not altered by these chemicals.
Topics: Adult; Affect; Afferent Pathways; Antipruritics; Female; Histamine; Histamine Agonists; Humans; Leg; Male; Mechanoreceptors; Menthol; Nerve Fibers, Unmyelinated; Nociceptors; Peroneal Nerve; Radial Nerve; Touch Perception; Young Adult
PubMed: 35020516
DOI: 10.1152/jn.00310.2021 -
Experimental Brain Research May 2012The purpose of the study was to investigate the interactions between two stimuli-menthol and nicotine-both of which activate the olfactory and the trigeminal system.... (Randomized Controlled Trial)
Randomized Controlled Trial
The purpose of the study was to investigate the interactions between two stimuli-menthol and nicotine-both of which activate the olfactory and the trigeminal system. More specifically, we wanted to know whether menthol at different concentrations modulates the perception of burning and stinging pain induced by nicotine stimuli in the human nose. The study followed an eightfold randomized, double-blind, cross-over design including 20 participants. Thirty phasic nicotine stimuli at one of the two concentrations (99 and 134 ng/mL) were applied during the entire experiment every 1.5 min for 1 s; tonic menthol stimulation at one of the three concentrations (0.8, 1.5 and 3.4 μg/mL) or no-menthol (placebo control conditions) was introduced after the 15th nicotine stimulus. The perceived intensities of nicotine's burning and stinging pain sensations, as well as perceived intensities of menthol's odor, cooling and pain sensations, were estimated using visual analog scales. Recorded estimates of stinging and burning sensations induced by nicotine initially decreased (first half of the experiment) probably due to adaptation/habituation. Tonic menthol stimulation did not change steady-state nicotine pain intensity estimates, neither for burning nor for stinging pain. Menthol-induced odor and cooling sensations were concentration dependent when combined with low-intensity nicotine stimuli. Surprisingly, this dose dependency was eliminated when combining menthol stimuli with high-intensity nicotine stimuli. There was no such nicotine effect on menthol's pain sensation. In summary, we detected interactions caused by nicotine on menthol perception for odor and cooling but no effect was elicited by menthol on nicotine pain sensation.
Topics: Adult; Analysis of Variance; Cross-Sectional Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Interactions; Female; Humans; Linear Models; Male; Menthol; Middle Aged; Nicotine; Nicotinic Agonists; Odorants; Olfactory Pathways; Pain; Pain Measurement; Physical Stimulation; Psychophysics; Rhinometry, Acoustic; Sensory Thresholds; Smell; Time Factors; Young Adult
PubMed: 22434343
DOI: 10.1007/s00221-012-3063-2 -
Nicotine & Tobacco Research : Official... Dec 2010Menthol cigarette smokers may find it harder to quit smoking than smokers of nonmenthol cigarettes. (Review)
Review
INTRODUCTION
Menthol cigarette smokers may find it harder to quit smoking than smokers of nonmenthol cigarettes.
METHODS
We conducted a systematic review of published studies examining the association between menthol cigarette smoking and cessation. Electronic databases and reference lists were searched to identify studies published through May 2010, and results were tabulated.
RESULTS
Ten studies were located that reported cessation outcomes for menthol and nonmenthol smokers. Half of the studies found evidence that menthol smoking is associated with lower odds of cessation, while the other half found no such effects. The pattern of results in these studies suggest that the association between smoking menthol cigarettes and difficulty quitting is stronger in (a) racial/ethnic minority populations, (b) younger smokers, and (c) studies carried out after 1999. This pattern is consistent with an effect that relies on menthol to facilitate increased nicotine intake from fewer cigarettes where economic pressure restricts the number of cigarettes smokers can afford to purchase.
CONCLUSIONS
There is growing evidence that certain subgroups of smokers find it harder to quit menthol versus nonmenthol cigarettes. There is a need for additional research, and particularly for studies including adequately powered and diverse samples of menthol and nonmenthol smokers, with reliable measurement of cigarette brands, socioeconomic status, and biomarkers of nicotine intake.
Topics: Humans; Menthol; Smoking; Smoking Cessation
PubMed: 21177366
DOI: 10.1093/ntr/ntq166 -
Tobacco Control Apr 2023To estimate the effect of menthol use and transitions in use (switching to or from menthol) on short-term and long-term cessation from cigarette smoking and whether this...
OBJECTIVES
To estimate the effect of menthol use and transitions in use (switching to or from menthol) on short-term and long-term cessation from cigarette smoking and whether this differed across demographic groups (age, sex, race).
METHODS
We compared the probability of 30+ day and 12-month abstinence from cigarette smoking by menthol use status using two cohorts of US adult cigarette smokers who attempted to quit smoking in the Population Assessment of Tobacco and Health (wave 1 to wave 3 and wave 2 to wave 4; n=5759), inverse probability of treatment weighting and adjusted risk ratios (aRRs).
RESULTS
Using menthol (vs non-menthol) prior to a quit attempt decreased the probability of 30+ day abstinence by 28% (aRR=0.78; 95% CI 0.67 to 0.91) and the probability of 12-month abstinence by 53% (aRR=0.65; 95% CI 0.47 to 0.88). Additionally, switching from menthol (vs maintaining menthol use) increased the probability of 30+ day abstinence by 58% (aRR=1.58; 95% CI 1.00 to 2.50) and the probability of 12-month abstinence by 97% (aRR=1.86; 95% CI 0.92 to 3.74). Switching to menthol (vs maintaining non-menthol use) was associated with a lower probability of 30+ day (aRR=0.70; 95% CI 0.42 to 1.16) and 12-month abstinence (aRR=0.64; 95% CI 0.30 to 1.36), but these associations were imprecise. The effects of menthol use on impaired quitting were slightly larger for non-Hispanic Black smokers, but not different for other demographic groups.
CONCLUSION
These results demonstrate that menthol impaired menthol smokers' attempts to quit smoking but switching from menthol improved success. This suggests that removing menthol may improve menthol smokers' success during quit attempts.
Topics: Adult; Humans; Smokers; Smoking Cessation; Menthol; Tobacco Products; Health Behavior; Nicotiana
PubMed: 34230056
DOI: 10.1136/tobaccocontrol-2021-056596 -
BMJ Open Apr 2022Although the Food and Drug Administration banned other characterising flavours in cigarettes, menthol cigarettes are still available to consumers. Young adult new...
INTRODUCTION
Although the Food and Drug Administration banned other characterising flavours in cigarettes, menthol cigarettes are still available to consumers. Young adult new smokers are initiating with menthol cigarettes, such that the prevalence of young adults menthol versus non-menthol smokers is increasing. Experimentation with menthol cigarettes is associated with progression to regular smoking and nicotine dependence. This ongoing clinical trial in young adult smokers measures appeal and the reinforcing value of smoking menthol versus non-menthol cigarettes and the impact of these variables on changes in smoking behaviour at a 6-month follow-up.
METHODS AND ANALYSIS
Reinforcement for menthol smoking is assessed in the laboratory using a validated behavioural economic choice task, and appeal is measured in the natural environment using ecological momentary assessment (EMA). Analyses will examine differences between menthol and non-menthol cigarette smoking on measures of subjective response in the laboratory and via EMA, and how subjective response mediates the association between menthol preference at baseline and smoking outcomes at follow-up.
ETHICS AND DISSEMINATION
This protocol was approved by the University of Oklahoma Health Sciences Center Institutional Review Board (#10581). The findings will isolate the unique effects of menthol in smoking and will help inform regulatory decisions about the abuse liability of menthol cigarettes. Findings will be disseminated through peer-reviewed journal articles and presentations at national and international conferences.
TRIAL REGISTRATION NUMBER
NCT03953508.
Topics: Humans; Menthol; Smokers; Smoking; Tobacco Products; Tobacco Use Disorder; Young Adult
PubMed: 35487522
DOI: 10.1136/bmjopen-2021-058823 -
Nicotine & Tobacco Research : Official... Oct 2021Cigarette smoking is disproportionately common among sexual minorities. While menthol market share has increased in the past decade, research on menthol cigarette...
INTRODUCTION
Cigarette smoking is disproportionately common among sexual minorities. While menthol market share has increased in the past decade, research on menthol cigarette smoking among sexual minorities is scant. For this study, we examined menthol cigarette smoking in the United States, by sex and sexual identity using a nationally representative sample of adults.
AIMS AND METHODS
We pooled data from the 2015-2019 National Survey on Drug Use and Health. We used chi-square tests and multivariable logistic regression models to examine (1) past 30-day cigarette use, (2) past 30-day menthol use, and (3) menthol preference among adults who have smoked cigarettes in the past 30 days for the following groups: heterosexual/straight males, heterosexual/straight females, gay males, gay/lesbian females, bisexual males, and bisexual females. Data were analyzed in September 2020.
RESULTS
Bivariate analyses revealed that prevalence of cigarette smoking and menthol cigarette smoking were higher among sexual minorities compared with heterosexual respondents, and that preference for menthol was highest among lesbian/gay and bisexual females who smoke. Multivariable models showed that compared with heterosexual females who smoke, odds of menthol preference were lower among heterosexual/straight and bisexual males who smoke, and higher among bisexual females.
CONCLUSIONS
Our study found that menthol preference was disproportionately high among sexual minorities who smoke-bisexual and gay/lesbian females who smoke in particular. Research is needed to understand why menthol use is common among sexual minorities who smoke.
IMPLICATIONS
Using data from a nationally representative study, this study makes a unique contribution to literature by identifying differences in menthol smoking between sexual minority subgroups. Specifically, we found that menthol smoking was highest among sexual minority females (ie, lesbian/gay and bisexual females) compared with other sexual minorities. These findings highlight the need for targeted interventions to prevent menthol cigarette initiation among sexual minorities, as well as to promote smoking cessation among sexual minorities who smoke menthol cigarettes, with an emphasis on sexual minority females. Future research should examine the impact of a potential menthol ban on these inequalities.
Topics: Adult; Cigarette Smoking; Female; Humans; Male; Menthol; Sexual and Gender Minorities; Smoke; Tobacco Use; United States
PubMed: 34255831
DOI: 10.1093/ntr/ntab101 -
The Clinical Respiratory Journal Dec 2023About 40% of nonsmall cell lung cancers (NSCLCs) have already progressed in an advanced stage at the time of diagnosis. Development of effective prevention and therapy...
BACKGROUND
About 40% of nonsmall cell lung cancers (NSCLCs) have already progressed in an advanced stage at the time of diagnosis. Development of effective prevention and therapy approaches against NSCLC is critical for reducing mortality. As a fundamental ingredient of peppermint oil, menthol has been demonstrated to possess an antitumor activity in several types of carcinomas. However, the potential role of menthol on NSCLC has not been reported. The present study aims to investigate the effect and underlying mechanism of menthol on proliferation, apoptosis, and mobility of human lung adenocarcinoma.
METHODS
Cell apoptosis was examined by MTT and flow cytometry. The motility of cells was determined by Transwell assay. Western blot analysis was performed to determine expression level of proteins. In vivo model of nude mice was established for evaluating the influence of menthol on tumorigenicity of A549 cells. The expression lentiviral vector of Akt was established in NSCLC cells for further verifying the inhibiting effect of menthol on survival and mobility of NSCLC cells via Akt pathway.
RESULTS
The results showed that menthol promoted A549 cell apoptosis, suppressed cell proliferation, and motility by altering the phosphorylated protein level of Akt. Menthol enhanced the expression level of Bax while decreasing expression of Bcl-2, Caspase-3, and MMPs proteins. In vivo experiments suggested that menthol exhibited an inhibitory effect in tumor growth on xenografts. These results were further validated in Akt over-expressed A549 and H1299 cells.
CONCLUSIONS
Menthol could display an inhibitory effect on NSCLC cells through Akt signaling pathway, making it a potential target for NSCLC treatment.
Topics: Animals; Mice; Humans; Proto-Oncogene Proteins c-akt; Lung Neoplasms; Menthol; Mice, Nude; Carcinoma, Non-Small-Cell Lung; Apoptosis; Cell Proliferation; Carcinoma; Lung; Cell Line, Tumor
PubMed: 38012058
DOI: 10.1111/crj.13713 -
Substance Abuse Treatment, Prevention,... Aug 2021The potential impact of menthol versus non-menthol cigarette use on smoking behaviors is an intensely scrutinized topic in the public health arena. To date, several... (Meta-Analysis)
Meta-Analysis Review
Assessing the evidence on the differential impact of menthol versus non-menthol cigarette use on smoking cessation in the U.S. population: a systematic review and meta-analysis.
BACKGROUND
The potential impact of menthol versus non-menthol cigarette use on smoking behaviors is an intensely scrutinized topic in the public health arena. To date, several general literature reviews have been conducted, but findings and conclusions have been discordant. This systematic review followed PRISMA guidelines to examine the Key Question, "Does menthol cigarette use have a differential impact on smoking cessation compared with non-menthol cigarette use?"
METHODS
Six databases-Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, MEDLINE, Embase and PsycInfo-were queried from inception to June 12, 2020. Articles comparing menthol versus non-menthol cigarette smokers in terms of at least one predefined smoking cessation outcome were included. Risk of bias was assessed using the Agency for Healthcare Research and Quality Evidence-Based Practice Center approach. A random-effects model utilizing the DerSimonian and Laird method to pool adjusted odds ratio was applied. Variations among pooled studies were assessed using Cochran's Q statistic, and heterogeneity was quantified using the inconsistency index (I).
RESULTS
Forty-three demographically adjusted studies (22 rated "good", 20 rated "fair", and one study rated "poor" individual study quality) comparing menthol and non-menthol smokers were qualitatively synthesized across the following measures (study count; strength of evidence): duration of abstinence (2; low); quit attempts (15; insufficient); rate of abstinence/quitting (29; moderate); change in smoking quantity/frequency (5; insufficient); and, return to smoking/relapse (2; insufficient). Overall, the qualitative synthesis failed to show a consistent trend for an association between menthol cigarette use and smoking cessation across outcomes. Meta-analyses found no difference between menthol and non-menthol cigarette use and either quit attempts or abstinence.
CONCLUSIONS
Given the lack of consistency or statistical significance in the findings-combined with a "low" overall strength of evidence grade, based on deficiencies of indirectness and inconsistency-no consistent or significant associations between menthol cigarette use and smoking cessation were identified. Recommendations for future studies include increased focus on providing longitudinal, adjusted data collected from standardized outcome measures of cessation to better inform long-term smoking cessation and menthol cigarette use. Such improvements should also be further considered in more methodologically rigorous systematic reviews characterized by objectivity, comprehensiveness, and transparency with the ultimate objective of better informing public health and policy decision making.
Topics: Humans; Menthol; Smoking; Smoking Cessation; Tobacco Products; Tobacco Use Cessation Devices; United States
PubMed: 34380503
DOI: 10.1186/s13011-021-00397-4 -
Nature Mar 2023The selective conversion of natural or synthetic neral to (1R,6S)-trans-isopiperitenol would enable and expedite sustainable routes to menthol and cannabinoids. However,...
The selective conversion of natural or synthetic neral to (1R,6S)-trans-isopiperitenol would enable and expedite sustainable routes to menthol and cannabinoids. However, this reaction has been considered impossible because its product is more reactive to the required acid catalysts than its starting material, resulting in several side products. We now show that an unsymmetric, strong and confined chiral acid, a highly fluorinated imino-imidodiphosphate, catalyses this process with excellent efficiency and selectivity. Expanding the method to other α,β-unsaturated aldehydes could enable access to new cannabinoids and menthol derivatives not readily accessible previously. Mechanistic studies suggest that the confined catalyst accomplishes this reaction by binding the product in an unreactive conformation, thereby preventing its decomposition. We also show how (1R,6S)-trans-isopiperitenol can be readily converted to pharmaceutically useful cannabinoids and menthol, each in the shortest and most atom-economic routes so far.
Topics: Cannabinoids; Catalysis; Menthol; Aldehydes; Halogenation; Chemistry Techniques, Synthetic; Acyclic Monoterpenes
PubMed: 36859552
DOI: 10.1038/s41586-023-05747-9