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

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Chen S. R., Pan H. L. (2006). Loss of TRPV1-expressing sensory neurons reduces spinal mu opioid receptors but paradoxically potentiates opioid analgesia. J. Neurophysiol. 95 Furthermore, it has been suggested that chronic smokers may have altered sensory irritation responses as a consequence of pulmonary remodeling and inflammatory reactions that are long-standing in the respiratory tract ( 70, 73, 74). The sensitivity of TRPA1 and TRPV1 receptors has been shown to be modified in chronic smokers, which may diminish the potential for menthol to act on local receptors to reduce inflammation ( 75, 76). Additionally, a chronic state of inflammation within the respiratory tract may induce changes to receptor sensitivity and responses to stimulation, reducing the anti-inflammatory effects of menthol ( 74). Indeed, in the research by Lin et al. ( 32), sub-chronic smoke exposure in mice (less than seven days) was sufficient to promote additional inflammatory reactions with menthol exposure, while this was not observed in acute exposure (20 minutes). This suggests that shorter periods of exposure may not be linked to additive inflammatory outcomes with menthol exposure ( 32). Therefore, the chronicity of smoking and the complex biochemical pathways that occur following exposure to menthol and cigarette smoke extracts (including nicotine) may account for variations in inflammatory responses to menthol in published research. Almost all the analgesic potency of menthol comes from its activation of TRPM8. It is worth noting that the term “analgesia” specifically refers to the relief of noxious heat, chemical stimuli, and mechanical allodynia. In patch-clamp recordings, menthol activated wild-type TRPM8 with the half maximal effective concentration (EC 50) of 185.4 ± 69.4 μM ( Xu et al., 2020). TRPM8 activation evokes an influx of Ca 2+ into the primary sensory neuron, leading to its activation and the propagation of action potentials. The activation of TRPM8 by menthol has been extensively studied in a variety of in vivo rodent models. Proudfoot et al. (2006) demonstrated that peripherally (4 mM) or centrally (200 nM) applied menthol, in a model of neuropathic pain (chronic compressive nerve injury, CCI) marked reverse behavioral reflex sensitization to noxious heat and mechanical stimulation. In addition, sensitization specific thermal and mechanical analgesia induced by TRPM8 activation has also been observed in focal demyelination of the sciatic nerve ( Proudfoot et al., 2006), Complete Freund’s adjuvant (CFA) intra plantar injection ( Proudfoot et al., 2006; Pan et al., 2012), and chemical stimulus (such as capsaicin, acrolein or cinnamaldehyde) ( Proudfoot et al., 2006; Liu et al., 2013). Systemic or topical application of menthol can dose-dependently increase pain threshold in rodents in hot plate tests ( Galeotti et al., 2002; Klein et al., 2010; Liu et al., 2013). In addition, direct evidence that TRPM8 may explain all the analgesic activity of menthol was provided by Liu et al. (2013) using genetic and pharmacological approaches in mice: the gene deletion and selective inhibitor (AMG2850) of TRPM8 completely eliminated the TRPM8-dependent analgesia on chemical stimuli, noxious heat, and inflammation. It is worth noting that the activation of TRPM8 can be regulated by neurotrophic factors ( Lippoldt et al., 2013, 2016), phosphatidylinositol bisphosphate (PIP 2) ( Premkumar et al., 2005; Rohács et al., 2005), Ca 2+-independent phospholipase A2 (iPLA2) and polyunsaturated fatty acids ( Andersson et al., 2007), forming a complex network.

Diver M. M., Cheng Y., Julius D. (2019). Structural insights into TRPM8 inhibition and desensitization. Science 365

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

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. Fernandes E. S., Fernandes M. A., Keeble J. E. (2012). The functions of TRPA1 and TRPV1: Moving away from sensory nerves. Br. J. Pharmacol. 166Gong K., Jasmin L. (2017). Sustained morphine administration induces TRPM8-dependent cold hyperalgesia. J. Pain 18

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 23Fan L., Balakrishna S., Jabba S. V., Bonner P. E., Taylor S. R., Picciotto M. R., et al. (2016). Menthol decreases oral nicotine aversion in C57BL/6 mice through a TRPM8-dependent mechanism. Tob. Control. 25

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. Dierkes P. W., Hochstrate P., Schlue W. R. (1997). Voltage-dependent Ca2+ influx into identified leech neurones. Brain Res. 746 Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China Colvin L. A. (2019). Chemotherapy-induced peripheral neuropathy: Where are we now? Pain 160 Suppl 1 Management of postoperative pain relieve suffering and leads to earlier mobilization, shortened hospital stay, reduced hospital costs, and increased patient satisfaction ( Gupta et al., 2010). Engelhard et al. (2019) observed a beneficial effect of cooling by a menthol-containing bandage during the rehabilitation phase after anterior cruciate ligament reconstruction. The reduction of muscle cross section within 30 days after surgery was prevented by menthol dressings, which highly contributed to rehabilitation success after 90 days of therapy and can reduce painkiller consumption ( Engelhard et al., 2019).Henderson B. J., Wall T. R., Henley B. M., Kim C. H., Nichols W. A., Moaddel R., et al. (2016). Menthol alone upregulates midbrain nachrs, alters nachr subtype stoichiometry, alters dopamine neuron firing frequency, and prevents nicotine reward. J. Neurosci. 36 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 Hawthorn M., Ferrante J., Luchowski E., Rutledge A., Wei X. Y., Triggle D. J. (1988). The actions of peppermint oil and menthol on calcium channel dependent processes in intestinal, neuronal and cardiac preparations. Aliment. Pharmacol. Ther. 2 Improved the analgesic efficacy of the tetracaine gel in part through enhanced percutaneous permeation Basso L., Aboushousha R., Fan C. Y., Iftinca M., Melo H., Flynn R., et al. (2019). TRPV1 promotes opioid analgesia during inflammation. Sci. Signal. 12:eaav0711. 10.1126/scisignal.aav0711