TDAG8, TRPV1, and ASIC3 involved in establishing hyperalgesic priming in experimental rheumatoid arthritis
Journal
Scientific Reports
Journal Volume
7
Pages
8870
Date Issued
2017
Author(s)
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. ? 2017 The Author(s).
SDGs
Other Subjects
Accn3 protein, mouse; acid sensing ion channel; biological marker; CD68 antigen, human; cytokine; differentiation antigen; G protein coupled receptor; GPCR25 protein, mouse; leukocyte antigen; TRPV1 receptor; vanilloid receptor; animal; arthralgia; blood; complication; disease model; experimental arthritis; female; gene expression; genetics; hyperalgesia; immunohistochemistry; immunology; knockout mouse; macrophage; male; metabolism; mouse; pathology; pathophysiology; rheumatoid arthritis; Acid Sensing Ion Channels; Animals; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Arthralgia; Arthritis, Experimental; Arthritis, Rheumatoid; Biomarkers; Cytokines; Disease Models, Animal; Female; Gene Expression; Hyperalgesia; Immunohistochemistry; Macrophages; Male; Mice; Mice, Knockout; Receptors, G-Protein-Coupled; TRPV Cation Channels
Type
journal article