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      Shakuyakukanzoto attenuates oxaliplatin-induced cold dysesthesia by inhibiting the expression of transient receptor potential melastatin 8 in mice

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          Abstract

          Oxaliplatin-induced peripheral neuropathy characterized especially as cold dysesthesia is a major dose-limiting side effect of the drug and is very difficult to control. In the present study, we examined whether the traditional herbal formulation Shakuyakukanzoto (SKT: 芍藥甘草湯Sháo Yào Gān Cǎo Tāng) could relieve oxaliplatin-induced cold dysesthesia in mice. The inhibitory mechanisms were also investigated. Repetitive administration of SKT (0.1–1.0 g/kg) starting from the day after oxaliplatin injection inhibited cold dysesthesia in a dose-dependent manner. Our previous report has shown that the mRNA expression of transient receptor potential melastatin 8 (TRPM8), characterized as a cold-sensing cation channel, is increased in the dorsal root ganglia of mice treated with oxaliplatin. In addition, TRPM8 antagonist TC-I 2014 (10 and 30 mg/kg) also attenuated cold dysesthesia in oxaliplatin-treated mice. Taken together, it is suggested that TRPM8 is involved in the cold dysesthesia induced by oxaliplatin. Repetitive administration of SKT inhibited the mRNA expression of TRPM8 induced by oxaliplatin in the dorsal root ganglia. These results suggested that prophylactic repetitive administration of SKT is effective in preventing the exacerbation of oxaliplatin-induced cold dysesthesia by inhibiting the mRNA expression of TRPM8 in the dorsal root ganglia.

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          A TRP channel that senses cold stimuli and menthol.

          Andrea Peier, Aziz Moqrich, Anne C Hergarden … (2002)
          A distinct subset of sensory neurons are thought to directly sense changes in thermal energy through their termini in the skin. Very little is known about the molecules that mediate thermoreception by these neurons. Vanilloid Receptor 1 (VR1), a member of the TRP family of channels, is activated by noxious heat. Here we describe the cloning and characterization of TRPM8, a distant relative of VR1. TRPM8 is specifically expressed in a subset of pain- and temperature-sensing neurons. Cells overexpressing the TRPM8 channel can be activated by cold temperatures and by a cooling agent, menthol. Our identification of a cold-sensing TRP channel in a distinct subpopulation of sensory neurons implicates an expanded role for this family of ion channels in somatic sensory detection.
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            Chemotherapy-induced peripheral neurotoxicity: A critical analysis : CIPN: A Critical Analysis

            Susanna B. Park, David Goldstein, Arun V. Krishnan … (2013)
            With a 3-fold increase in the number of cancer survivors noted since the 1970s, there are now over 28 million cancer survivors worldwide. Accordingly, there is a heightened awareness of long-term toxicities and the impact on quality of life following treatment in cancer survivors. This review will address the increasing importance and challenge of chemotherapy-induced neurotoxicity, with a focus on neuropathy associated with the treatment of breast cancer, colorectal cancer, testicular cancer, and hematological cancers. An overview of the diagnosis, symptomatology, and pathophysiology of chemotherapy-induced peripheral neuropathy will be provided, with a critical analysis of assessment strategies, neuroprotective approaches, and potential treatments. The review will concentrate on neuropathy associated with taxanes, platinum compounds, vinca alkaloids, thalidomide, and bortezomib, providing clinical information specific to these chemotherapies. © 2013 American Cancer Society, Inc.
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              Distinct expression of TRPM8, TRPA1, and TRPV1 mRNAs in rat primary afferent neurons with adelta/c-fibers and colocalization with trk receptors.

              Kimiko Kobayashi, Tetsuo Fukuoka, Koichi Obata … (2005)
              The transient receptor potential (TRP) superfamily of cation channels contains four temperature-sensitive channels, named TRPV1-4, that are activated by heat stimuli from warm to that in the noxious range. Recently, two other members of this superfamily, TRPA1 and TRPM8, have been cloned and characterized as possible candidates for cold transducers in primary afferent neurons. Using in situ hybridization histochemistry and immunohistochemistry, we characterized the precise distribution of TRPA1, TRPM8, and TRPV1 mRNAs in the rat dorsal root ganglion (DRG) and trigeminal ganglion (TG) neurons. In the DRG, TRPM8 mRNA was not expressed in the TRPV1-expressing neuronal population, whereas TRPA1 mRNA was only seen in some neurons in this population. Both A-fiber and C-fiber neurons expressed TRPM8, whereas TRPV1 was almost exclusively seen in C-fiber neurons. All TRPM8-expressing neurons also expressed TrkA, whereas the expression of TRPV1 and TRPA1 was independent of TrkA expression. None of these three TRP channels were coexpressed with TrkB or TrkC. The TRPM8-expressing neurons were more abundant in the TG compared with the DRG, especially in the mandibular nerve region innervating the tongue. Our data suggest heterogeneity of TRPM8 and TRPA1 expression by subpopulations of primary afferent neurons, which may result in the difference of cold-sensitive primary afferent neurons in sensitivity to chemicals such as menthol and capsaicin and nerve growth factor. Copyright (c) 2005 Wiley-Liss, Inc.
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                Author and article information

                Contributors
                Tsugunobu Andoh
                Journal
                Journal ID (nlm-ta): J Tradit Complement Med
                Journal ID (iso-abbrev): J Tradit Complement Med
                Title: Journal of Traditional and Complementary Medicine
                Publisher: Elsevier
                ISSN (Electronic): 2225-4110
                Publication date PMC-release: 20 February 2016
                Publication date Collection: January 2017
                Publication date (Electronic): 20 February 2016
                Volume: 7
                Issue: 1
                Pages: 30-33
                Affiliations
                [a ]Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan
                [b ]Tokyo Medical and Dental University, Tokyo, Japan
                Author notes
                [∗ ]Corresponding author. Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan. Tel.: +81 76 434 7511; fax: +81 76 434 5045. andoht@ 123456pha.u-toyama.ac.jp
                Article
                Publisher ID: S2225-4110(16)00019-5
                DOI: 10.1016/j.jtcme.2016.01.003
                PMC ID: 5198822
                PubMed ID: 28053885
                SO-VID: 3882de3b-34ac-4ada-a6d5-ec50f4e4a49c
                Copyright © Copyright © 2016, Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC.
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 28 July 2015
                Date revision received : 18 January 2016
                Date accepted : 26 January 2016
                Categories
                Subject: Short Communication

                Keywords: oxaliplatin,shakuyakukanzoto,trpm8,cold dysesthesia,dorsal root ganglia
                Data availability:
                Keywords: oxaliplatin, shakuyakukanzoto, trpm8, cold dysesthesia, dorsal root ganglia

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