WHAT IS KNOWN AND OBJECTIVE Menthol has been used as a non-opioid pain reliever since ancient times. A modern understanding of its molecular mechanism of action could form the basis for generating targets for discovery of novel non-opioid analgesic drugs. METHODS The PubMed database was queried using search words related to menthol, pain and analgesia. The results were limited to relevant preclinical studies and clinical trials and reviews published in English during the past 5 years, which yielded 31 reports. The bibliographies of these articles were sources of additional supporting articles. RESULTS Menthol is a selective activator of transient receptor potential melastatin-8 (TRPM8) channels and is also a vasoactive compound. As a topical agent, it acts as a counter-irritant by imparting a cooling effect and by initially stimulating nociceptors and then desensitizing them. Topically applied menthol may also activate central analgesic pathways. At high concentrations, menthol may generate cold allodynia. WHAT IS NEW AND CONCLUSIONS Recent elucidation of TRPM8 channels has provided a molecular basis for understanding the molecular action of menthol and its ability to produce both a cooling sensation and reduction in pain associated with a wide variety of pain(ful) conditions. The more modern mechanistic understanding of menthol and its pharmacologic mechanism of action may lead to an expanded role for this substance in the search for replacements for opioid analgesics, particularly those that can be applied topically.

中文翻译：

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薄荷醇在局部镇痛产品中的作用和作用机理。

已知和目标薄荷醇自古以来就被用作非阿片类药物的止痛药。对它的分子作用机理的现代理解可以为产生新的非阿片类镇痛药的靶标奠定基础。方法使用与薄荷醇，疼痛和镇痛有关的搜索词查询PubMed数据库。结果仅限于过去5年中以英文发表的相关临床前研究，临床试验和评论，产生了31篇报告。这些文章的参考文献是其他支持文章的来源。结果薄荷醇是瞬态受体电位melastatin-8（TRPM8）通道的选择性激活剂，也是一种血管活性化合物。作为外用剂，它通过赋予凉爽作用并首先刺激伤害感受器，然后使其脱敏，从而起到抗刺激作用。局部应用薄荷醇也可能激活中枢镇痛途径。在高浓度下，薄荷醇可能会产生冷性异常性疼痛。什么是新事物和结论最近对TRPM8通道的阐明为理解薄荷醇的分子作用及其产生凉快感和减轻与多种疼痛状况相关的疼痛的能力提供了分子基础。对薄荷醇及其药理作用机理的更现代的机械性理解可能会导致该物质在寻找阿片类镇痛药的替代品（尤其是可局部应用的镇痛药）的替代中发挥更大的作用。局部应用薄荷醇也可能激活中枢镇痛途径。在高浓度下，薄荷醇可能会产生冷性异常性疼痛。什么是新事物和结论最近对TRPM8通道的阐明为理解薄荷醇的分子作用及其产生凉快感和减轻与多种疼痛症状相关的疼痛的能力提供了分子基础。对薄荷醇及其药理作用机理的更现代的机械性理解可能会导致该物质在寻找阿片类镇痛药的替代品（尤其是可局部应用的镇痛药）的替代中发挥更大的作用。局部应用薄荷醇也可能激活中枢镇痛途径。在高浓度下，薄荷醇可能会产生冷性异常性疼痛。什么是新事物和结论最近对TRPM8通道的阐明为理解薄荷醇的分子作用及其产生凉快感和减轻与多种疼痛症状相关的疼痛的能力提供了分子基础。对薄荷醇及其药理作用机理的更现代的机械性理解可能会导致该物质在寻找阿片类镇痛药的替代品（尤其是可局部应用的镇痛药）的替代中发挥更大的作用。什么是新事物和结论最近对TRPM8通道的阐明为理解薄荷醇的分子作用及其产生凉快感和减轻与多种疼痛症状相关的疼痛的能力提供了分子基础。对薄荷醇及其药理作用机理的更现代的机械性理解可能会导致该物质在寻找阿片类镇痛药的替代品（尤其是可局部应用的镇痛药）的替代中发挥更大的作用。什么是新事物和结论最近对TRPM8通道的阐明为理解薄荷醇的分子作用及其产生凉快感和减轻与多种疼痛症状相关的疼痛的能力提供了分子基础。对薄荷醇及其药理作用机理的更现代的机械性理解可能会导致该物质在寻找阿片类镇痛药的替代品（尤其是可局部应用的镇痛药）的替代中发挥更大的作用。