The relationship between intra-articular biomarkers and characteristics of pain sensitization in patients with knee osteoarthritis: a pre-liminary analysis

Aim: Synovitis and central sensitization are common features in knee osteoarthritis (KOA), however, the relationship between them is unclear. Therefore, this study aimed to investigate the association between sensitization and intra-articular biomarker levels in KOA patients.
Methods: Seventeen KOA patients scheduled for total knee arthroplasty in UZ Brussel were included. Pressure pain thresholds (PPTs), temporal summation (TS) and conditioned pain modulation (CPM) were assessed. During surgery, synovial fluid was obtained to determine biomarker levels. Multiple linear regression was used to assess the association between pain sensitization parameters and intra-articular biomarker levels. Four independent predictors were created: inflammation (log(CXCL-10*CXCL2/IL-10)), cartilage degeneration (log(MMP-1*MMP-7)), sensitization (log(BDNF*NGF)), and ageing (log(CXCL-9)). Regression models were corrected for BMI, sex and age.
Results: Two out of eight PPT locations around the knee (i.e. 1 and 8) seemed most relevant and were chosen as dependent variables in the regression model, besides the control sites; m. tibialis anterior and m. ext. carpi radialis longus. Log(CXCL-10) was inversely correlated with mean PPT at locations 1 and 8 (Pearson’s r: -0.518 and -0.502). No regression model could significantly predict the mean PPT at locations 1 and 8 around the knee, the mean PPT at the m. tibialis anterior and m. ext. carpi radialis longus, or the absolute TS. However, 61.8% (R²=0.618) of the variation in relative CPM effect could be significantly explained by the cartilage degeneration predictor (p=0.022; β= 0.8).
Conclusion: Top-down pain inhibition can partially be predicted by intra-articular MMP-1 and MMP-7. However, more research on this topic is recommended.