{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T23:44:57Z","timestamp":1791935097186,"version":"4.3.4"},"reference-count":28,"publisher":"Georg Thieme Verlag KG","funder":[{"name":"Hebei Medical Science Research Project","award":["2024128"],"award-info":[{"award-number":["2024128"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Knee Surg"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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. 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 &gt;\u20093 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. 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\u2009&lt;\u20090.05). Serum SPON1 and APOE levels were significantly higher in the CPSP-positive group (both p\u2009&lt;\u20090.05), and positively correlated (r\u2009=\u20090.253, p\u2009&lt;\u20090.05). The combination of SPON1 and APOE had an area under the curve (AUC) of 0.908 (95% CI: 0.864\u20130.951), indicating good discriminative ability between CPSP-positive and CPSP-negative patients, superior to SPON1 alone (Z\u2009=\u2009\u2212\u20093.144, p\u2009=\u20090.002) and APOE alone (Z\u2009=\u2009\u2212\u20093.078, p\u2009=\u20090.002). Multivariable analysis showed more years of education was a protective factor, whereas higher preoperative PD-Q and WOMAC scores and elevated serum SPON1 and APOE levels were risk factors for CPSP. 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.<\/jats:p>","DOI":"10.1055\/a-2968-6034","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T23:18:14Z","timestamp":1790637494000},"source":"Crossref","is-referenced-by-count":0,"title":["Association of Preoperative Serum SPON1 and APOE Levels with Chronic Postsurgical Pain after Total Knee Arthroplasty"],"prefix":"10.1055","author":[{"given":"Tao","family":"Feng","sequence":"additional","affiliation":[{"name":"Shijiazhuang People's Hospital, Hebei, China","place":["Shijiazhuang"],"department":["Department of Spine Surgery"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hu","family":"Ren","sequence":"additional","affiliation":[{"name":"Shijiazhuang People's Hospital, Hebei, China","place":["Shijiazhuang"],"department":["Department of Spine Surgery"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhui","family":"Cao","sequence":"additional","affiliation":[{"name":"Shijiazhuang People's Hospital, Hebei, China","place":["Shijiazhuang"],"department":["Department of Orthopedic Surgery"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liya","family":"Di","sequence":"additional","affiliation":[{"name":"Shijiazhuang People's Hospital, Hebei, China","place":["Shijiazhuang"],"department":["Department of Cardiac Surgery"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiguang","family":"Tian","sequence":"additional","affiliation":[{"name":"Shijiazhuang People's Hospital, Hebei, China","place":["Shijiazhuang"],"department":["Department of Orthopedic 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replacement surgery: a narrative review","volume":"25","author":"J Murphy","year":"2024","journal-title":"Int J Mol Sci"},{"issue":"01","key":"ref4","doi-asserted-by":"crossref","first-page":"2420863","DOI":"10.1080\/07853890.2024.2420863","article-title":"Regulating lipid metabolism in osteoarthritis: a complex area with important future therapeutic potential","volume":"56","author":"X Chen","year":"2024","journal-title":"Ann Med"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1498981","DOI":"10.3389\/fnins.2025.1498981","article-title":"Dysregulation of lipid metabolism, energy production, and oxidative stress in myalgic encephalomyelitis\/chronic fatigue syndrome, Gulf War Syndrome and fibromyalgia","volume":"19","author":"L Davis","year":"2025","journal-title":"Front Neurosci"},{"issue":"05","key":"ref6","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1194\/jlr.TR119000468","article-title":"Lipid rafts in glial cells: role in neuroinflammation and pain 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Fernandez","year":"2021","journal-title":"J Alzheimers Dis Rep"},{"issue":"05","key":"ref10","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.3390\/cells9051275","article-title":"SPON1 can reduce amyloid beta and reverse cognitive impairment and memory dysfunction in Alzheimer's disease mouse model","volume":"9","author":"S Y Park","year":"2020","journal-title":"Cells"},{"issue":"02","key":"ref11","doi-asserted-by":"crossref","first-page":"e1132","DOI":"10.1002\/iid3.1132","article-title":"Silencing of secreted phosphoprotein 1 attenuates sciatic nerve injury-induced neuropathic pain: regulating extracellular signal-regulated kinase and neuroinflammatory signaling pathways","volume":"12","author":"H Xie","year":"2024","journal-title":"Immun Inflamm Dis"},{"issue":"03","key":"ref12","doi-asserted-by":"crossref","first-page":"e122","DOI":"10.1097\/j.pain.0000000000002728","article-title":"Insights into the pleiotropic relationships between chronic back pain and 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Allen","year":"2021","journal-title":"Ann Intern Med"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1483570","DOI":"10.3389\/fpsyt.2024.1483570","article-title":"Anxiety and depression prevalence and associated factors in patients with knee osteoarthritis","volume":"15","author":"Q Feng","year":"2025","journal-title":"Front Psychiatry"},{"issue":"16","key":"ref20","doi-asserted-by":"crossref","first-page":"2747","DOI":"10.1242\/dev.015289","article-title":"The C. elegans F-spondin family protein SPON-1 maintains cell adhesion in neural and non-neural tissues","volume":"135","author":"W M Woo","year":"2008","journal-title":"Development"},{"issue":"01","key":"ref21","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1159\/000541542","article-title":"Analyzing the role of specific damage-associated molecular patterns-related genes in osteoarthritis and investigating the association between \u03b2-amyloid and apolipoprotein E isoforms","volume":"16","author":"F Yuan","year":"2024","journal-title":"J Innate Immun"},{"issue":"03","key":"ref22","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1385\/JMN:23:3:205","article-title":"A dual role for apolipoprotein e in neuroinflammation: anti- and pro-inflammatory activity","volume":"23","author":"L Guo","year":"2004","journal-title":"J Mol Neurosci"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.2147\/JPR.S345496","article-title":"Prevalence and predictors of chronic pain with two-year follow-up after knee arthroplasty","volume":"15","author":"M Tian","year":"2022","journal-title":"J Pain Res"},{"issue":"01","key":"ref24","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1186\/s13018-024-04778-w","article-title":"Risk factors of chronic postoperative pain after total knee arthroplasty: a systematic review","volume":"19","author":"J Li","year":"2024","journal-title":"J Orthop Surg 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