TDAG8, TRPV1, and ASIC3 involved in establishing hyperalgesic priming in experimental rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA), characterized by chronic inflammation of synovial joints, is often associated with ongoing pain and increased pain sensitivity. High hydrogen ion concentration (acidosis) found in synovial fluid in RA patients is associated with disease severity. Acidosis signaling acting on proton-sensing receptors may contribute to inflammation and pain. Previous studies focused on the early phase of arthritis (<5 weeks) and used different arthritis models, so elucidating the roles of different proton-sensing receptors in the chronic phase of arthritis is difficult. We intra-articularly injected complete Freund’s adjuvant into mice once a week for 4 weeks to establish chronic RA pain. Mice with knockout of acid-sensing ion channel 3 (ASIC3) or transient receptor potential/vanilloid receptor subtype 1 (TRPV1) showed attenuated chronic phase (>6 weeks) of RA pain. Mice with T-cell death-associated gene 8 (TDAG8) knockout showed attenuated acute and chronic phases of RA pain. TDAG8 likely participates in the initiation of RA pain, but all three genes, TDAG8, TRPV1, and ASIC3, are essential to establish hyperalgesic priming to regulate the chronic phase of RA pain.

Contributors

Wei-Hsin Sun:

ORCID: http://orcid.org/0000-0003-3009-520X

[e-mail]

Journal

Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2045-2322

Publication date (Electronic): 21 August 2017

Publication date PMC-release: 21 August 2017

Publication date Collection: 2017

Volume: 7

Affiliations

[1 ]ISNI 0000 0004 0532 3167, GRID grid.37589.30, Department of Life Sciences, , National Central University, ; Zhongli, Taoyuan city Taiwan

[2 ]ISNI 0000 0004 0572 7815, GRID grid.412094.a, Department of Anesthesiology, , National Taiwan University Hospital Hsin-Chu Branch, ; Hsin-Chu, Taiwan

[3 ]ISNI 0000 0001 0425 5914, GRID grid.260770.4, Institute of Microbiology and Immunology, , National Yang-Ming University, ; Taipei, Taiwan

[4 ]Department of Immunology, Cathy General Hospital, Taipei, Taiwan

Article

Publisher ID: 9200

DOI: 10.1038/s41598-017-09200-6

PMC ID: 5566336

PubMed ID: 28827659

Copyright statement: © The Author(s) 2017

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Subject: Article

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