Osteoarthritis (OA) is a chronic degenerative
musculoskeletal disease that causes articular cartilage degeneration and
chronic pain. Research into OA animal models suggests that elevated
NGF levels in the synovium contribute to
pain and central sensitization (CS). However, it is unclear whether synovial
NGF contributes to CS in patients with OA. We investigated the association between synovial
NGF expression and clinical assessments of
pain and CS in hip OA (
hOA) patients. We also aimed to identify which cells in the synovium of
hOA patients express
NGF. Sixty-six patients who received
total hip replacement and a diagnosis of
hOA were enrolled. We measured
NGF mRNA expression in synovial samples obtained from 50 patients using qPCR and analyzed the correlation of
NGF expression with the CS inventory (CSI) score and Japanese Orthopaedic Association (JOA) score, a clinical scoring system for OA. To identify the synovial cells expressing
NGF, we analyzed
NGF mRNA expression in CD14+ and CD14- cells, which represent macrophage-rich and fibroblast-rich fractions, respectively, extracted from 8 patients. To further identify which macrophage subtypes express
NGF, we examined
NGF mRNA expression in CD14high and CD14low cells sorted from 8 patients. Synovial
NGF mRNA expression was negatively correlated with JOA score but positively correlated with CSI score (JOA
pain, r = -0.337, P = 0.017; CSI score, r = 0.358, P = 0.011). Significantly greater levels of
NGF were observed in CD14- cells compared to CD14+ cells (P = 0.036) and in CD14high cells compared to CD14low cells (P = 0.008). In conclusion, synovial
NGF expression is correlated with the degree of
pain and CS in
hOA patients.
NGF is predominantly expressed in synovial fibroblasts. Further, CD14high synovial macrophages expressed higher levels of
NGF. Our results may provide a novel
NGF-targeted therapeutic strategy for
hOA pain.