Association of Preoperative Serum SPON1 and APOE Levels with Chronic Postsurgical Pain after Total Knee Arthroplasty

Objective: To investigate the association of preoperative serum Secreted Phosphoprotein 1 (SPON1) and Apolipoprotein E (APOE) with chronic postsurgical pain (CPSP) following total knee arthroplasty (TKA), providing a hypothetical basis for validation studies. Methods: This retrospective study included 218 patients who underwent unilateral TKA between March 2023 and February 2025 with 6-month follow-up. CPSP was defined as a knee pain score >3 on the Visual Analog Scale (VAS) during movement at 6 months postoperatively. Demographic and clinical data, preoperative and postoperative pain scores, painDETECT questionnaire (PD-Q), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Hospital Anxiety and Depression Scale (HADS) scores, and preoperative serum SPON1 and APOE levels were collected. ROC curve was performed to evaluate the performance of serum SPON1 and APOE in discriminating CPSP-positive from CPSP-negative patients after TKA. Multivariable logistic regression analysis was performed to explore risk factors for CPSP following TKA. Results: Fifty-five patients were CPSP-positive and 163 were CPSP-negative. The CPSP-positive group had fewer years of education, higher prevalence of diabetes mellitus, longer duration of preoperative pain and knee osteoarthritis (KOA), and higher preoperative VAS, PD-Q, WOMAC, and HADS scores (all P<0.05). Serum SPON1 and APOE levels were significantly higher in the CPSP-positive group (both P<0.05), and positively correlated (r=0.253, P<0.05). The combination of SPON1 and APOE had an AUC of 0.908 (95% CI: 0.864–0.951), indicating good discriminative ability between CPSP-positive and CPSP-negative patients, superior to SPON1 alone (Z = -3.144，P=0.002) APOE alone (Z = -3.078，P=0.002). Multivariable analysis showed more years of education were a protective factor, whereas higher preoperative PD-Q and WOMAC scores and elevated serum SPON1 and APOE levels were risk factors for CPSP. Conclusion: Serum SPON1 and APOE levels were associated with CPSP after TKA, and their combination showed favorable discriminative ability. Because the model was not validated, these results represent preliminary evidence of an association; the clinical value of these markers as potential biomarkers requires confirmation in prospective studies.