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Nociceptive Roles of TRPM2 Ion Channel in Pathologic Pain

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Abstract

Pain is a protective mechanism that enables us to avoid potentially harmful environments. However, when pathologically persisted and aggravated under severely injured or inflamed conditions, pain often reduces the quality of life and thus is considered as a disease to eliminate. Inflammatory and/or neuropathic mechanisms may exaggerate interactions between damaged tissues and neural pathways for pain mediation. Similar mechanisms also promote the communication among cellular participants in synapses at spinal or higher levels, which may amplify nociceptive firing and subsequent signal transmission, deteriorating the pain sensation. In this pathology, important cellular players are afferent sensory neurons, peripheral immune cells, and spinal glial cells. Arising from damage of injury, overloaded interstitial and intracellular reactive oxygen species (ROS) and intracellular Ca2+ are key messengers in the development and maintenance of pathologic pain. Thus, an ROS-sensitive and Ca2+-permeable ion channel that is highly expressed in the participant cells might play a critical role in the pathogenesis. Transient receptor potential melastatin subtype 2 (TRPM2) is the unique molecule that satisfies all of the requirements: the sensitivity, permeability, and its expressing cells. Notable progress in delineating the role of TRPM2 in pain has been achieved during the past decade. In the present review, we summarize the important findings in the key cellular components that are involved in pathologic pain. This overview will help to understand TRPM2-mediated pain mechanisms and speculate therapeutic strategies by utilizing this updated information.

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Acknowledgements

This work was supported by grants from the National Research Foundation of Korea (2017R1A2B2001817 and 2017M3C7A1025600). The authors declare that there is no conflict of interest regarding the publication of this article.

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Authors and Affiliations

  1. Department of Psychiatry and Program in Neuroscience, McLean Hospital, Harvard Medical School, Belmont, MA, 02478, USA

    Yongwoo Jang

  2. Department of Biomedical Sciences and Department of Physiology, College of Medicine, Korea University, Seoul, 02841, South Korea

    Pyung Sun Cho & Sun Wook Hwang

  3. Department of Pharmacy, College of Pharmacy, CHA University, Gyeonggi, 11160, South Korea

    Young Duk Yang

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  1. Yongwoo Jang
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  2. Pyung Sun Cho
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  3. Young Duk Yang
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  4. Sun Wook Hwang
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Correspondence to Young Duk Yang or Sun Wook Hwang.

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Jang, Y., Cho, P.S., Yang, Y.D. et al. Nociceptive Roles of TRPM2 Ion Channel in Pathologic Pain. Mol Neurobiol 55, 6589–6600 (2018). https://doi.org/10.1007/s12035-017-0862-2

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  • DOI: https://doi.org/10.1007/s12035-017-0862-2

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