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Tackling Pain Associated with Rheumatoid Arthritis: Proton-Sensing Receptors

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Advances in Pain Research: Mechanisms and Modulation of Chronic Pain

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1099))

Abstract

Rheumatoid arthritis (RA), characterized by chronic inflammation of synovial joints, is often associated with ongoing pain and increased pain sensitivity. Chronic pain that comes with RA turns independent, essentially becoming its own disease. It could partly explain that a significant number (50%) of RA patients fail to respond to current RA therapies that focus mainly on suppression of joint inflammation. The acute phase of pain seems to associate with joint inflammation in early RA. In established RA, the chronic phase of pain could be linked to inflammatory components of neuron-immune interactions and noninflammatory components. Accumulating evidence suggests that the initial inflammation and autoimmunity in RA (preclinical RA) begin outside of the joint and may originate at mucosal sites and alterations in the composition of microbiota located at mucosal sites could be essential for mucosal inflammation, triggering joint inflammation. Fibroblast-like synoviocytes in the inflamed joint respond to cytokines to release acidic components, lowering pH in synovial fluid. Extracellular proton binds to proton-sensing ion channels, and G-protein-coupled receptors in joint nociceptive fibers may contribute to sensory transduction and release of neurotransmitters, leading to pain and hyperalgesia. Activation of peripheral sensory neurons or nociceptors further modulates inflammation, resulting in neuroinflammation or neurogenic inflammation. Peripheral and central nerves work with non-neuronal cells (such as immune cells, glial cells) in concert to contribute to the chronic phase of RA-associated pain. This review will discuss actions of proton-sensing receptors on neurons or non-neuronal cells that modulate RA pathology and associated chronic pain, and it will be beneficial for the development of future therapeutic treatments.

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Authors and Affiliations

  1. Department of Life Sciences, National Central University, Taoyuan City, Taiwan

    Wei-Hsin Sun & Shih-Ping Dai

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  1. Wei-Hsin Sun
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Correspondence to Wei-Hsin Sun .

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  1. Division of Neuroscience, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

    Bai-Chuang Shyu

  2. Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), Okazaki, Aichi, Japan

    Makoto Tominaga

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Sun, WH., Dai, SP. (2018). Tackling Pain Associated with Rheumatoid Arthritis: Proton-Sensing Receptors. In: Shyu, BC., Tominaga, M. (eds) Advances in Pain Research: Mechanisms and Modulation of Chronic Pain. Advances in Experimental Medicine and Biology, vol 1099. Springer, Singapore. https://doi.org/10.1007/978-981-13-1756-9_5

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