Renova Menthol Sensitive Tissues Handkerchiefs (6 Packs of 9) - Extra Soft

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Cortellini A., Verna L., Cannita K., Napoleoni L., Parisi A., Ficorella C., et al. (2017). Topical menthol for treatment of chemotherapy-induced peripheral neuropathy. Indian J. Palliat. Care 23 Cliff M. A., Green B. G. (1994). Sensory irritation and coolness produced by menthol: Evidence for selective desensitization of irritation. Physiol. Behav. 56 The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher’s note TRP channels were first identified in a mutant breed of the fruit fly Drosophila, known as “transient receptor potential” in 1969 ( 78). From the control of cell motility and phagocytosis to the generation and release of inflammatory mediators, TRP channel-mediated effects on immune cells are undoubtedly numerous. Menthol has the potential to become a novel treatment for inflammatory illnesses due to the wide functional significance of TRP channels in inflammation and immunity ( 79). This section provides information on the role of TRP channels associated with menthol, such as TRPM8, in inflammatory diseases. TRPM8 (Transient receptor potential cation channel subfamily melastatin member 8) Sundar et al. ( 69) and Kaur et al. ( 70) have noted that tobacco flavoring can influence the inflammatory response of cigarette smoke inhalation in the lungs. A variety of flavors added to tobacco have been associated with decreased viability of cells, decreased cell numbers in cultures, and increased levels of inflammation after exposure compared with unflavored tobacco, including when flavored with menthol ( 69). It is proposed that menthol acts on the TRPA1 receptor to activate an inflammatory response in lung parenchyma based on cell experiments and animal models of cigarette smoke inhalation ( 30, 71). Markers of inflammation elevated with menthol flavored smoke inhalation included cyclo-oxygenase-2 (COX-2) and prostaglandin levels, which are recognized as drivers of an acute local inflammatory reaction in various tissue types ( 30).

The application of menthol to cutaneous tissue and submucosal tissue is common in clinical practice for the alleviation of pain and to promote a cooling effect ( 54). However, there is increasing interest in the potential for menthol to exert anti-inflammatory effects when applied to the skin and associated tissues, including inflammation associated with pathological conditions and processes. Andersen et al. ( 39) reported that the application of a 40% menthol-based cream to an area of irritation and inflammation on the forearm leads to a reduction in pain, neurogenic inflammation, and hyperalgesia (high responsiveness to sensations). This study utilized topical 10% trans-cinnamaldehyde application to elicit the cutaneous symptoms, with the treatment of menthol simultaneously noted to reduce pain intensity (P<0.01), neurogenic inflammation (P<0.01), and hyperalgesia (P<0.05) compared with symptoms when menthol was not applied. HC: Conceptualization, Data Curation, Project Administration, Writing - Original Draft. XA: Conceptualization, Funding Acquisition, Writing - Review & Editing. All authors contributed to the article and approved the submitted version. Funding Higashi Y., Kiuchi T., Furuta K. (2010). Efficacy and safety profile of a topical methyl salicylate and menthol patch in adult patients with mild to moderate muscle strain: A randomized, double-blind, parallel-group, placebo-controlled, multicenter study. Clin. Ther. 32 Cortés-Montero E., Rodríguez-Muñoz M., Ruiz-Cantero M. D. C., Cobos E. J., Sánchez-Blázquez P., Garzón-Niño J. (2020). Calmodulin supports TRPA1 channel association with opioid receptors and glutamate NMDA receptors in the nervous tissue. Int. J. Mol. Sci. 22:229. 10.3390/ijms22010229Cheang W. S., Lam M. Y., Wong W. T., Tian X. Y., Lau C. W., Zhu Z., et al. (2013). Menthol relaxes rat aortae, mesenteric and coronary arteries by inhibiting calcium influx. Eur. J. Pharmacol. 702 Skin wound healing involves an array of biochemical, molecular, cellular, and tissue processes [ 1]. The physiological events that lead to wound repair can be divided into three dynamic phases: inflammatory, proliferative, and tissue remodeling. These overlapping steps encompass a network of cellular communication that ensures the progress of the healing process [ 2]. Dhaka A., Murray A. N., Mathur J., Earley T. J., Petrus M. J., Patapoutian A. (2007). TRPM8 is required for cold sensation in mice. Neuron 54 Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China Freilinger T., Anttila V., de Vries B., Malik R., Kallela M., Terwindt G. M., et al. (2012). Genome-wide association analysis identifies susceptibility loci for migraine without aura. Nat. Genet. 44

Gillis D. J., Vellante A., Gallo J. A., D’Amico A. P. (2020). Influence of menthol on recovery from exercise-induced muscle damage. J. Strength Cond. Res. 34 Hemmings H. C., Jr., Akabas M. H., Goldstein P. A., Trudell J. R., Orser B. A., Harrison N. L. (2005). Emerging molecular mechanisms of general anesthetic action. Trends Pharmacol. Sci. 26Chen Y., Geis C., Sommer C. (2008). Activation of TRPV1 contributes to morphine tolerance: Involvement of the mitogen-activated protein kinase signaling pathway. J. Neurosci. 28 Borhani Haghighi A., Motazedian S., Rezaii R., Mohammadi F., Salarian L., Pourmokhtari M., et al. (2010). Cutaneous application of menthol 10% solution as an abortive treatment of migraine without aura: A randomised, double-blind, placebo-controlled, crossed-over study. Int. J. Clin. Pract. 64 Amato A., Liotta R., Mulè F. (2014). Effects of menthol on circular smooth muscle of human colon: Analysis of the mechanism of action. Eur. J. Pharmacol. 740 Results: The decrease in pro-inflammatory cytokines and related inflammatory markers, as well as associated pathway activation, was found to play the greatest role in the protective effects of menthol against inflammatory damage or association with protection against chronic inflammation. Heimes K., Hauk F., Verspohl E. J. (2011). Mode of action of peppermint oil and (-)-menthol with respect to 5-HT3 receptor subtypes: Binding studies, cation uptake by receptor channels and contraction of isolated rat ileum. Phytother. Res. 25

Improved the analgesic efficacy of the tetracaine gel in part through enhanced percutaneous permeation The biological effects of menthol have generally been linked to analgesic effects when topically applied to the skin, as well as an increasing interest in respiratory or systemic effects following inhalation due to the popularity of menthol cigarettes ( 26). Analgesic effects via the TRPM8 receptor and associated TRP channels, are well described and are closely related to the cooling effects seen upon TRPM8 activation ( 6). Nevertheless, the role of menthol in inflammatory pain relief and in alleviating inflammatory responses associated with cigarette smoking has raised interest in the potential anti-inflammatory mechanisms of this compound ( 14). The remainder of this paper considers the influence of menthol on inflammation in available studies to appreciate the effects of menthol and the mechanisms accounting for those effects. Influence of menthol on inflammation OverviewAndersen H. H., Melholt C., Hilborg S. D., Jerwiarz A., Randers A., Simoni A., et al. (2017). Antipruritic effect of cold-induced and transient receptor potential-agonist-induced counter-irritation on histaminergic itch in humans. Acta Derm. Venereol. 97 Dierkes P. W., Hochstrate P., Schlue W. R. (1997). Voltage-dependent Ca2+ influx into identified leech neurones. Brain Res. 746 Taken together, studies exploring the protective effects of menthol against inflammatory damage, or association with protection against chronic inflammation, are indicative of potential therapeutic applications of the compound. However, it is vital to note the limitations of the studies completed to date. One main limitation is that most of the studies are either in vitro or based on animal models of human disease, which may limit our direct application to human pathology. While menthol has been extensively used therapeutically in humans, demonstration of a clear anti-inflammatory effect should be sought and evaluated using biochemical markers or inflammation in a pathological context. Furthermore, while the evidence for the anti-inflammatory effects of menthol is compelling, additional insights may be needed to clarify the mechanisms of action and the clinical relevance of any anti-inflammatory effects. This is especially noteworthy considering the evidence for the pro-inflammatory impact of inhaled menthol when combined with cigarette smoking ( 42). Inflammatory cascades are complex and closely related to immunological function and antioxidant activity in multiple tissues; further delineation of these mechanisms and pathways is needed to truly appreciate the potential for menthol, which appears to be a molecule with multiple cellular targets, as a therapeutic anti-inflammatory compound. Author contributions Glyn-Jones S., Palmer A. J., Agricola R., Price A. J., Vincent T. L., Weinans H., et al. (2015). Osteoarthritis. Lancet 386

Fisher K., Lefebvre C., Coderre T. J. (2002). Antinociceptive effects following intrathecal pretreatment with selective metabotropic glutamate receptor compounds in a rat model of neuropathic pain. Pharmacol. Biochem. Behav. 73 Cold hypersensitivity alleviated, no change in receptive field size was observed or in heat, dynamic brush, or electrically evoked responses Colvin L. A., Bull F., Hales T. G. (2019). Perioperative opioid analgesia-when is enough too much? A review of opioid-induced tolerance and hyperalgesia. Lancet 393Fernández J. A., Skryma R., Bidaux G., Magleby K. L., Scholfield C. N., McGeown J. G., et al. (2011). Voltage- and cold-dependent gating of single TRPM8 ion channels. J. Gen. Physiol. 137 Menthol is also an allosteric non-competitive inhibitor of the 5-hydroxytryptamine type 3 (5-HT 3) receptor ( Heimes et al., 2011; Ashoor et al., 2013b; Walstab et al., 2014; Ziemba et al., 2015), which may explain its effective antiemetic properties. Gong K., Jasmin L. (2017). Sustained morphine administration induces TRPM8-dependent cold hyperalgesia. J. Pain 18 Filippov I. B., Vladymyrova I. A., Kuliieva Ie M., Skryma R., Prevarskaia N., Shuba, et al. (2009). [Modulation of the smooth muscle contractions of the rat vas deferens by TRPM8 channel agonist menthol]. Fiziol Zh (1994) 55 Andersen H. H., Poulsen J. N., Uchida Y., Nikbakht A., Arendt-Nielsen L., Gazerani P. (2015). Cold and L-menthol-induced sensitization in healthy volunteers–a cold hypersensitivity analogue to the heat/capsaicin model. Pain 156