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

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In the physiological state, high concentrations of menthol can induce TRPM8 sensitization and promote the development of cold allodynia and cold hyperalgesia by excessively lowering the cold pain threshold. Menthol-induced cold hypersensitivity is believed to primarily rely on direct sensitization of TRPM8 on Aδ and C-fibers ( Andersen et al., 2014). Numerous studies indicate that high concentration of menthol can cause hyperalgesia in cold perception in rodents (>10% wt/vol or >640 mM for mice topically, Tajino et al., 2007), which may make menthol valuable in pre-clinical screening of analgesic agents for cold hyperalgesia ( Rossi et al., 2006; Tajino et al., 2007), and it provides a theoretical basis for the establishment of experimental cold hyperalgesia pain model in human with topically high concentration of menthol (>30% wt/vol for healthy subjects, Hatem et al., 2006). Andersen 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 Cheang 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 Methods: Using the pharmacopeias and electronic databases, including Web of Science, PubMed, and CNKI, this study analyzed the relevant research articles and review articles from 2002 to 2022 and concluded those results and conjectures to finish this article. Gudin J. A., Dietze D. T., Hurwitz P. L. (2020). Improvement of pain and function after use of a topical pain relieving patch: Results of the RELIEF study. J. Pain Res. 13

The treatment of skin wounds is responsible for the largest investment in research and development among all skin diseases [ 7] and is among the most critical issues in medical science [ 5]. Clinically, several drugs have been developed, aiming to accelerate the wound healing process but presenting side effects or low efficiency. In modern medical sciences, searching for drugs that accelerate wound healing with minimal pain, discomfort, and scarring is a promising area of research [ 6]. Several studies have successfully tested the effects of medicinal plants in skin wound healing, in which the extracts or their isolated compounds accelerated skin wound closure, inhibited local inflammation, and increased cellular antioxidant defense [ 8, 9]. Plant-based therapy is known to accelerate wound healing as well as maintaining the aesthetics in a natural way [ 10]; this is the reason why more than 70% of wound healing pharmaceutical products are derived from plants [ 11].Gupta A., Kaur K., Sharma S., Goyal S., Arora S., Murthy R. S. (2010). Clinical aspects of acute post-operative pain management & its assessment. J. Adv. Pharm. Technol. Res. 1

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 Chen S. R., Pan H. L. (2005). Distinct roles of group III metabotropic glutamate receptors in control of nociception and dorsal horn neurons in normal and nerve-injured Rats. J. Pharmacol. Exp. Ther. 312 Fritschy J. M., Panzanelli P., Tyagarajan S. K. (2012). Molecular and functional heterogeneity of GABAergic synapses. Cell. Mol. Life Sci. 69 Menthol is a monocyclic monoterpene found in the essential oil of some species of the genus Mentha [ 12]. Menthol is an agonist of transient receptor potential melastatin-8 channels, cold receptors in the sensory nerves of the skin. For this reason, menthol exerts a cooling sensation when applied to the skin and mucosal membranes [ 13]. The activation of TRPM8 channels does not influence skin wound healing [ 14]. Menthol also activates TRPV3 channels and presents a bimodal effect in TRPA1 and TRPV1 [ 15]. Some studies have shown that the activation of TRPV3 channels contributes to wound healing in the skin [ 16], oral mucosa [ 17], and corneal epithelial cells [ 18]. Furthermore, the inhibition of TRPA1 and TRPV1 channels is involved with the pain-relieving effect of menthol [ 19]. Menthol is widely used in cosmetics, as well as in the medicinal preparations for the relief of pain [ 20] and respiratory conditions [ 21].Glyn-Jones S., Palmer A. J., Agricola R., Price A. J., Vincent T. L., Weinans H., et al. (2015). Osteoarthritis. Lancet 386 Similar to chronic inflammation seen in other tissues, neuroinflammatory responses are linked to a range of disease states, including dementia ( 65). The protective effects of menthol administration have also been observed in the context of Parkinson’s disease models ( 44). Specifically, menthol administration has been shown to be protective against lipopolysaccharide-induced inflammatory damage to dopaminergic neurons, which are characteristically affected by Parkinson’s disease pathology ( 44). Menthol demonstrated an anti-inflammatory effect, with inhibition of pro-inflammatory enzymes and cytokines via activation of the nuclear factor kappa B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) pathways. During the neuroinflammatory process, Du et al. ( 44) found that menthol inhibited the increase in phosphorylation levels of p65, ERK1/2, JNK1/2, and AKT in an in vitro experiment. Menthol has been shown to increase the activation of dopaminergic neurons, but also decrease neuronal firing in cellular studies, suggesting that additional effects on the stimulation of dopaminergic neurons may also be relevant in Parkinson’s disease ( 66, 67). In terms of Alzheimer’s disease, research indicates that menthol therapy that pharmacologically raises body temperature also results in a reduction in tau phosphorylation in the brain, but not in conjunction with an inflammatory response ( 68). However, this is an area that requires further exploration, given the relative paucity of literature on menthol’s effects on neuroinflammatory pathways. Lung inflammation

Bautista D. M., Jordt S. E., Nikai T., Tsuruda P. R., Read A. J., Poblete J., et al. (2006). TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell 124 Airaksinen O. V., Kyrklund N., Latvala K., Kouri J. P., Grönblad M., Kolari P. (2003). Efficacy of cold gel for soft tissue injuries: A prospective randomized double-blinded trial. Am. J. Sports Med. 31 Hans M., Wilhelm M., Swandulla D. (2012). Menthol suppresses nicotinic acetylcholine receptor functioning in sensory neurons via allosteric modulation. Chem. Senses 37Cabezas-Cerrato J. (1998). The prevalence of clinical diabetic polyneuropathy in Spain: A study in primary care and hospital clinic groups. Neuropathy spanish study group of the spanish diabetes society (SDS). Diabetologia 41

Boyd A., Bleakley C., Hurley D. A., Gill C., Hannon-Fletcher M., Bell P., et al. (2019). Herbal medicinal products or preparations for neuropathic pain. Cochrane Database Syst. Rev. 4:Cd010528. 10.1002/14651858.CD010528.pub4 Post-exercise myalgia and delayed onset muscle soreness (DOMS) are common symptoms after exercise and physical activity. Stefanelli et al. (2019) found that DOMS reduced corticospinal excitability and after the administration of menthol-based topical analgesic, there was a reduction in pain, which was accompanied by increased corticospinal inhibition. Although ice application is considered the traditional method for post-exercise pain relief, Johar et al. (2012) demonstrated that compared to ice, the topical menthol-based analgesic decreased perceived discomfort to a greater extent and permitted greater tetanic forces to be produced, and the effectiveness of ice for acute injury has not been proven in any clinical trials and may even be harmful ( Bleakley et al., 2004). Airaksinen et al. (2003) showed that topical menthol gels not only provide excellent pain relief, but also promote recovery in patients with exercise-related soft tissue injuries. Higashi et al. (2010) reported in a double-blind randomized controlled trial that a single 8-h patch containing methyl salicylate and menthol significantly alleviated pain associated with mild to moderate muscle strain in these adult patients compared to patients receiving a placebo patch. {"type":"clinical-trial","attrs":{"text":"NCT02100670","term_id":"NCT02100670"}}NCT02100670 is a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial performed to evaluate topical 1% diclofenac/3% menthol gel in treating ankle sprain, but no significant improvement was observed with topical 1% diclofenac/3% menthol gel compared with placebo, 1% diclofenac, or 3% menthol gel in treating pain from ankle sprain ( Lai et al., 2017). 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 Neuropathic pain is defined as pain caused by a lesion or disease of the somatosensory nervous system and is a major therapeutic challenge. Common causes of neuropathic pain include cerebrovascular accident, multiple sclerosis or spinal cord injury, or peripheral nervous system, for example, painful diabetic neuropathy, postherpetic neuralgia, or surgery ( Boyd et al., 2019). The first reported use of menthol in neuropathic pain dates to 1870, when menthol oil was successfully used to treat neuropathic facial pain.Gold M. S., Weinreich D., Kim C. S., Wang R., Treanor J., Porreca F., et al. (2003). Redistribution of Na(V)1.8 in uninjured axons enables neuropathic pain. J. Neurosci. 23 Caterina M. J., Schumacher M. A., Tominaga M., Rosen T. A., Levine J. D., Julius D. (1997). The capsaicin receptor: A heat-activated ion channel in the pain pathway. Nature 389 Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China Low cold sensitivity at high concentration (10% and 40%); cold allergy at low concentrations (0.01−1%)