Background: Patients with persistent pain due to osteoarthritis (OA) complain of multiple symptoms that cannot be explained solely by structural changes. A poor correlation exists between structural and inflammatory changes in OA and pain levels. Central sensitization (CS) has been identified as a factor that induces chronic pain in patients with OA. Although it is important to identify osteoarthritis patients with CS components, the prevalence and characteristics of CS, especially those in patients with hip OA, are not well understood. Thus, we aimed to determine the prevalence and characteristics of CS in patients with hip OA, in this study. Methods: The CS Inventory (CSI), used as a non-invasive routine clinical tool to evaluate the presence of CS 1 month before surgery in 100 patients with hip OA, was measured at our outpatient clinic, and the data were retrospectively reviewed. We determined the number of patients with a CSI score of 40 points or higher and assessed the relationships between the CSI score and clinical factors (including age, duration of hip pain, degree pain at rest and on activity, by using the visual analogue scale [VAS] and the Harris Hip Score) using the Spearman's correlation coefficient. Results: The mean age of participants was 63.9 ± 11.6 years, and there were 15 men and 85 women. All patients had hip OA, categorised as advanced and terminal stage (Tönnis grade 2-3) on preoperative plain radiography. The mean duration of hip pain was 4.2 ± 4.4 years. The mean CSI score was 19.5 ± 11.3 and 5 (5.0%) of the patients had a score of 40 or more points. CSI scores correlated significantly only with VAS pain at rest (r = 0.348, P < 0.001). Conclusion: In this study, 1 out of every 20 hip OA patients had CS components. CSI scores were significantly correlated with pain at rest in hip OApatients. CS approaches to hip OA may be one of the treatment options for pain at rest.

Expression of CD163, a scavenger receptor specifically expressed by monocytes and macrophages, is elevated in the synovial tissue of patients with knee osteoarthritis (OA) compared with healthy controls. However, the association between CD163 expression in the synovium and pain in OA patients is unclear. We investigated the correlation between synovial CD163 expression and resting and active pain levels in patients with hip osteoarthritis (HOA). To investigate the possible contribution of CD163+ subsets to pain pathogenesis, we compared pain‐related cytokine expression and M1/M2 macrophage marker expression in CD163+ and CD163− cells. We performed flow cytometric analysis to study the CD163+ cell population. We also examined pain‐related cytokine expression and M1/M2 macrophage marker expression on CD163+ CD14high and CD163+ CD14low cells using cell sorting. Synovial CD163 expression significantly correlated with resting pain levels (p = 0.006; R = 0.321), but not active pain levels (p = 0.155; R = 0.169). Expression of the M1 macrophage marker CD80 was significantly higher in CD163+ than CD163− cells (p = 0.010), as was the expression of M2 macrophage markers CD206 and IL10 (CD206, p = 0.014; IL10, p = 0.005), and TNFA and IL1B (TNFA, p = 0.002; IL1B, p = 0.001). TNFA expression was significantly higher in CD163+ CD14low than CD163+ CD14high cells, while IL1B, IL10, and CD206 expression were comparable among these subsets. Our findings suggest that CD163 expression is associated with higher resting pain scores. As TNF‐α plays a role in the pain process, CD163+ CD14low cells expressing TNFA may be a potent contributor to the pathogenesis of resting pain in HOA.

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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.

Background: Patients with persistent pain due to osteoarthritis (OA) complain of multiple symptoms that cannot be explained solely by structural changes. A poor correlation exists between structural and inflammatory changes in OA and pain levels. Central sensitization (CS) has been identified as a factor that induces chronic pain in patients with OA. Although it is important to identify osteoarthritis patients with CS components, the prevalence and characteristics of CS, especially those in patients with hip OA, are not well understood. Thus, we aimed to determine the prevalence and characteristics of CS in patients with hip OA, in this study. Methods: The CS Inventory (CSI), used as a non-invasive routine clinical tool to evaluate the presence of CS 1 month before surgery in 100 patients with hip OA, was measured at our outpatient clinic, and the data were retrospectively reviewed. We determined the number of patients with a CSI score of 40 points or higher and assessed the relationships between the CSI score and clinical factors (including age, duration of hip pain, degree pain at rest and on activity, by using the visual analogue scale [VAS] and the Harris Hip Score) using the Spearman’s correlation coefficient. Results: The mean age of participants was 63.9±11.6 years, and there were 15 men and 85 women. All patients had hip OA, categorised as advanced and terminal stage (Tönnis grade 2–3) on preoperative plain radiography. The mean duration of hip pain was 4.2±4.4 years. The mean CSI score was 19.5±11.3 and 5 (5.0%) of the patients had a score of 40 or more points. CSI scores correlated significantly only with VAS pain at rest (r=0.348, P<0.001). Conclusion: In this study, 1 out of every 20 hip OA patients had CS components. CSI scores were significantly correlated with pain at rest in hip OA patients. CS approaches to hip OA may be one of the treatment options for pain at rest.