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

• Published in: Scientific reports Vol. 7; no. 1; pp. 8870 - 14
• Main Authors: Hsieh, Wei-Shan, Kung, Chia-Chi, Huang, Shir-Ly, Lin, Shih-Chang, Sun, Wei-Hsin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21.08.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 13/51; 42/89; 631/378/1959/2605; 64/60; 692/699/1670/498; Acid Sensing Ion Channels - genetics; Acid Sensing Ion Channels - metabolism; Acidosis; Animal models; Animals; Antigens, CD - metabolism; Antigens, Differentiation, Myelomonocytic - metabolism; Arthralgia - etiology; Arthralgia - physiopathology; Arthritis, Experimental; Arthritis, Rheumatoid - complications; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - pathology; Autoimmune diseases; Biomarkers; Capsaicin receptors; Cell death; Chronic pain; Cytokines - blood; Cytokines - metabolism; Disease Models, Animal; Female; Gene Expression; Humanities and Social Sciences; Hydrogen ion concentration; Hydrogen ions; Hyperalgesia - etiology; Hyperalgesia - physiopathology; Immunohistochemistry; Joint diseases; Lymphocytes T; Macrophages - immunology; Macrophages - metabolism; Macrophages - pathology; Male; Mice; Mice, Knockout; multidisciplinary; Pain; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Rheumatoid arthritis; Science; Science (multidisciplinary); Synovial fluid; Transient receptor potential proteins; TRPV Cation Channels - genetics; TRPV Cation Channels - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-09200-6

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.