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

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Within the gastrointestinal tract, inflammatory reactions are associated with a number of adverse conditions and pathologies ( 47). As menthol can be administered orally and is safe for human consumption, the potential for menthol to exert anti-inflammatory effects in the gastrointestinal tract is attractive, provided these effects can be demonstrated in pathological contexts. Evidence to date suggests that menthol may reduce inflammation associated with gastric ulceration ( 37), gastro-oesophageal reflux-associated inflammation ( 33), and colitis ( 41, 43). Chen 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

The contrasting findings of menthol exposure on inflammatory responses in smokers may be dependent on a range of effects. For instance, it has been noted that menthol may alter the metabolism of nicotine, increasing systemic exposure to nicotine and slowing the metabolic clearance of nicotine and associated compounds in the lungs ( 35). Whether this increases the potential for more inflammation, which is associated with lung nicotine exposure, remains to be confirmed, but is one hypothesis as to why co-administration of menthol and nicotine may lead to heightened inflammation ( 70). Besides, the difference in constituents between commercial mentholated and non-mentholated cigarettes may also introduce confounding factors in the experiment. 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 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 Chemotherapy-induced peripheral neuropathy is a severe and painful adverse reaction of cancer treatment in patients. CIPN that occurs during chemotherapy, sometimes requiring dose reduction or cessation, impacting on survival ( Colvin, 2019). Menthol activated TRPM8 channels are a promising therapeutic target in CIPN ( Colvin, 2019). In Fallon et al. (2015), in a proof-of-concept study, determined that 82% of evaluable patients had an improvement in their total pain scores after 4−6 weeks of treatment with topical 1% menthol cream, and 50% had a clinically relevant reduction in pain scores of at least 30%. Cortellini et al. (2017) reported the remarkable treatment with menthol cream of a male patient with a history of metastatic colon cancer and previous chemotherapies who had neuropathy that impaired his quality of life and limited further chemotherapy. Another clinical study ( {"type":"clinical-trial","attrs":{"text":"NCT01855607","term_id":"NCT01855607"}}NCT01855607, as shown in Table 2) assessed whether 6 weeks of treatment with topical menthol twice daily would reduce CIPN in patients have completed adjuvant or neo-adjuvant Taxane based breast cancer therapy or Oxaliplatin based colon cancer chemotherapy. Recently, a phase II study ( {"type":"clinical-trial","attrs":{"text":"NCT04276727","term_id":"NCT04276727"}}NCT04276727, as shown in Table 2) used a special brain scan called functional magnetic resonance imaging (fMRI) to help determine whether topical menthol therapy has potential for CIPN patients. In a word, CIPN patients may benefit from the use of menthol, either during the treatment of patients complain of subjective improvement, lead to a better quality of life, and can be implemented without interruption of chemotherapy and effective chemotherapy dose delivery, which in turn lead to longer survival, is likely to be an effective potential palliative treatment option.Bandell M., Story G. M., Hwang S. W., Viswanath V., Eid S. R., Petrus M. J., et al. (2004). Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron 41 Cold hypersensitivity alleviated, no change in receptive field size was observed or in heat, dynamic brush, or electrically evoked responses 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

Huang S. M., Bisogno T., Trevisani M., Al-Hayani A., De Petrocellis L., Fezza F., et al. (2002). An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors. Proc. Natl. Acad. Sci. U.S.A. 99 Despite the uncertainty over the value of topical menthol in reducing inflammation that is established in the skin, the anti-inflammatory effects of menthol have been proposed to influence wound healing, as investigated by Rozza et al. ( 61). Skin wound healing is a complex process that includes an inflammatory phase, whereby reductions in inflammatory markers, including IL-6, have been linked to accelerated skin wound healing ( 61). In this study, the authors evaluated the effects of different periods of time of treatment with menthol (3, 7, or 14 days) in rats with skin wounds, comparing collagenase-based and menthol-based creams. The menthol-based cream led to accelerated healing within the first three days of treatment, which is consistent with a reduction in the initial inflammatory phase of wound healing when compared with collagenase-based creams. Furthermore, this healing was linked to a reduction in pro-inflammatory cytokines TNF-α and IL-6 (reduced expression of mRNA). Over time, menthol-based treatment was found to not only decrease pro-inflammatory cytokine levels through the inflammatory, proliferative, and remodeling phases of wound healing. Dessirier J. M., O’Mahony M., Carstens E. (2001). Oral irritant properties of menthol: Sensitizing and desensitizing effects of repeated application and cross-desensitization to nicotine. Physiol. Behav. 73

Introduction

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. Iftinca M., Basso L., Flynn R., Kwok C., Roland C., Hassan A., et al. (2020). Chronic morphine regulates TRPM8 channels via MOR-PKCβ signaling. Mol Brain 13:61. 10.118 Bautista D. M., Movahed P., Hinman A., Axelsson H. E., Sterner O., Högestätt E. D., et al. (2005). Pungent products from garlic activate the sensory ion channel TRPA1. Proc. Natl. Acad. Sci. U.S.A. 102 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 Descoeur J., Pereira V., Pizzoccaro A., Francois A., Ling B., Maffre V., et al. (2011). Oxaliplatin-induced cold hypersensitivity is due to remodelling of ion channel expression in nociceptors. EMBO Mol. Med. 3

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 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]. 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. 73Dani J. A., Bertrand D. (2007). Nicotinic acetylcholine receptors and nicotinic cholinergic mechanisms of the central nervous system. Annu. Rev. Pharmacol. Toxicol. 47 Diver M. M., Cheng Y., Julius D. (2019). Structural insights into TRPM8 inhibition and desensitization. Science 365 Studies showed that TRPM8 might affect in inflammation process by mediating the release of inflammatory cytokines ( 47, 81). NF-κB mediated TRPM8’s TNF-α inhibition ( 81). The study found that TRPM8 expression enhanced TRPM8-NF-κB interaction, decreasing NF-κB nuclear localization. On this basis, the suppression inhibited TNF-α gene transcription. TRPM8 agonists, such as menthol and icilin, are found to decrease the release of cytokines IL-1β, IL-6, and TNF-α from dendritic cells ( 47).

Fallon M. T., Storey D. J., Krishan A., Weir C. J., Mitchell R., Fleetwood-Walker S. M., et al. (2015). Cancer treatment-related neuropathic pain: Proof of concept study with menthol–a TRPM8 agonist. Support. Care Cancer 23 Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China Despite the published anti-inflammatory effects of menthol within experimental settings, there is evidence to suggest that in specific contexts, menthol may have pro-inflammatory effects or may induce inflammatory responses. This has been noted in the context of cigarette smoking, when inflammatory activity in human lung epithelial cells has been assessed ( 32). Specifically, Lin et al. ( 32) found that menthol cigarette smoke exposure led to more severe lung inflammation than non-menthol smoke inhalation in the context of sub-chronic exposure. With exposure for up to seven days, it was noted that lung inflammation was more severe when menthol smoke was inhaled, based on activation of epithelial and lung MAPK pathways via TRPM8, along with histopathological markers of lung inflammation. The authors also found that treatment with a TRPM8 inhibitor suppressed MAPK activation and subsequent lung inflammation ( 32). These findings build on previous in vitro work that suggested that exposure to menthol cigarette smoke increased reactive oxygen species sensitivity in lung parenchymal cells, increased TRPM8-mediated MAPK pathway activation, and promoted inflammatory responses to a greater degree than non-menthol smoke exposure.Andersen H. H., Olsen R. V., Møller H. G., Eskelund P. W., Gazerani P., Arendt-Nielsen L. (2014). A review of topical high-concentration L-menthol as a translational model of cold allodynia and hyperalgesia. Eur. J. Pain 18 Bleakley C., McDonough S., MacAuley D. (2004). The use of ice in the treatment of acute soft-tissue injury: A systematic review of randomized controlled trials. Am. J. Sports Med. 32 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