期刊
ANNALS OF THE RHEUMATIC DISEASES
卷 72, 期 2, 页码 265-270出版社
BMJ PUBLISHING GROUP
DOI: 10.1136/annrheumdis-2012-201703
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资金
- Morphosys AG
- National Health and Medical Research Council (NHMRC)
- NHMRC Senior Principal Research Fellowship
Objectives Better therapies are needed for inflammatory pain. In arthritis the relationship between joint pain, inflammation and damage is unclear. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is important for the progression of a number of inflammatory/autoimmune conditions including arthritis; clinical trials targeting its action in rheumatoid arthritis are underway. However, its contribution to inflammatory and arthritic pain is unknown. The aims of this study were to determine whether GM-CSF controls inflammatory and/or arthritic pain. Methods A model of inflammatory pain (complete Freund's adjuvant footpad), as well as two inflammatory arthritis models, were induced in GM-CSF-/- mice and development of pain (assessment of weight distribution) and arthritic disease (histology) was assessed. Pain was further assessed in a GM-CSF-driven arthritis (methylated bovine serum albumin/GM-CSF) model and the cyclooxygenase-dependence determined using indomethacin. Results GM-CSF was absolutely required for pain development in both the inflammatory pain and arthritis models, including for IL-1-dependent arthritic pain. Pain in a GM-CSF-driven arthritis model, but not the disease itself, was abolished by the cyclooxygenase inhibitor, indomethacin, indicating separate pathways downstream of GM-CSF for pain and arthritis control. Conclusions GM-CSF is key to the development of inflammatory and arthritic pain, suggesting that pain alleviation could result from trials evaluating its role in inflammatory/autoimmune conditions.
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