Expression of granulocyte macrophage-colony stimulating factor and its receptor in the synovium of osteoarthritis patients is negatively correlated with pain

Objectives. The crosstalk between the immune and nervous system in the regulation of OA pain is increasingly becoming evident. GM-CSF signals in both systems and might be a new treatment target to control OA pain. Anti GM-CSF treatment has analgesic effects in OA without affecting synovitis scores, suggesting that treatment effects are not caused by local anti-inflammatory effects. We aimed to evaluate whether expression of GM-CSF and its receptor GM-CSFra in synovial tissue is linked to synovial inflammation and/or knee pain in knee OA patients. Methods. Cartilage and synovial tissue of knee OA patients (n ¼ 20) was collected during total knee replacement. Cartilage damage was evaluated by histology and ex vivo matrix proteoglycan turnover. Synovial inflammation was evaluated by histology and ex vivo synovial production of TNF-a, (PGE ₂) and nitric oxide (NO). Numbers of synovial tissue cells expressing GM-CSF or GM-CSFra were determined by immunohistochemistry. Pain was evaluated using WOMAC questionnaire and visual analogue scale (VAS) knee pain. Results. Collected cartilage and synovial tissue had a typical OA phenotype with enhanced cartilage damage and synovial inflammation. GM-CSF and GM-CSFra expressing cells in the synovial sublining correlated negatively with knee pain. Cartilage damage and synovial inflammation did not correlate with knee pain. Conclusion. Unanticipated, the negative correlation between synovial tissue cells expressing GM-CSF(r) and OA knee pain suggests that local presence of these molecules does not promote pain, and that the role of GM-CSFr in OA pain is unrelated to local inflammation.