Correspondence to Dr Andrew D Cook, Department of Medicine, University of Melbourne, The Royal Melbourne Hospital, Parkville, VC 3010, Australia.
Ann Rheum Dis. 2013 Feb;72(2):265-70. doi: 10.1136/annrheumdis-2012-201703. Epub 2012 Jul 24.
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.
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.
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.
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.
需要更好的疗法来治疗炎性疼痛。在关节炎中，关节疼痛、炎症和损伤之间的关系尚不清楚。粒细胞-巨噬细胞集落刺激因子（GM-CSF）对于许多炎症/自身免疫性疾病的进展很重要，包括关节炎；针对其在类风湿关节炎中的作用的临床试验正在进行中。然而，其对炎症和关节炎性疼痛的贡献尚不清楚。本研究的目的是确定 GM-CSF 是否控制炎症和/或关节炎性疼痛。
在 GM-CSF(-/-) 小鼠中诱导炎症性疼痛（完全弗氏佐剂足垫）以及两种炎症性关节炎模型，并评估疼痛（体重分布评估）和关节炎疾病（组织学）的发展。在 GM-CSF 驱动的关节炎（甲基化牛血清白蛋白/GM-CSF）模型中进一步评估疼痛，并使用吲哚美辛确定环氧化酶依赖性。
GM-CSF 对于两种炎症性疼痛和关节炎模型的疼痛发展都是绝对必需的，包括 IL-1 依赖性关节炎性疼痛。在 GM-CSF 驱动的关节炎模型中，疼痛而非疾病本身被环氧化酶抑制剂吲哚美辛所消除，表明 GM-CSF 下游存在用于疼痛和关节炎控制的不同途径。
GM-CSF 是炎症和关节炎性疼痛发展的关键，这表明疼痛缓解可能源自评估其在炎症/自身免疫性疾病中的作用的试验。
