Background There is growing evidence that cytokines and adipokines are associated with osteoarthritis (OA) severity, progression, and severity of associated pain. However, the cytokine response to total knee arthroplasty (TKA) and its association with persistent postoperative pain is not well understood. This study aims to describe the perioperative systemic (plasma) and local (synovial fluid) cytokine profiles of patients who do and do not develop persistent pain after TKA.
Methods Patients undergoing primary unilateral TKA for end-stage OA were prospectively enrolled. Demographic and clinical data were gathered preoperatively and postoperatively. Synovial fluid was collected pre arthrotomy and plasma was collected at multiple time points before and after surgery. Persistent postoperative pain (PPP) was defined as Numerical Rating Score≥4 at 6 months. Cytokine levels were measured using the V-Plex Human Cytokine 30-Plex Panel (Mesoscale—Rockville, Maryland, USA). Cytokine levels were compared between PPP and minimal pain groups. Given that the study outcomes are exploratory, no adjustment was performed for multiple testing.
Results Incidence of persistent pain at 6 months post TKA was 15/162 (9.3%). Postoperative plasma levels of four cytokines were significantly different in patients who developed persistent postoperative pain: interleukin (IL)-10, IL-1β, vascular endothelial growth factor, and IL12/IL23p40. Significantly lower IL-10 levels in the prearthrotomy synovial fluid were associated with development of postoperative persistent pain.
Conclusions This prospective cohort study described a distinct acute perioperative inflammatory response profile in patients who developed persistent post-TKA pain, characterized by significant differences in four cytokines over the first 2 postoperative days. These results support the growing evidence that the patient-specific biologic response to surgery may influence longer-term clinical outcomes after TKA.
Trial registration number Clinicaltrials.gov NCT02626533.
- chronic pain
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information. All relevant data are included in the article or as uploaded supplementary information.
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Contributors AS: helped in data analysis, interpretation of results, manuscript preparation, and review. M-AM: helped in interpretation of results, manuscript preparation, and review. GB: helped in study data collection, interpretation of results, and manuscript review. HZ: conducted data analysis, interpretation of results, manuscript preparation, and review. VR: helped in study planning, data collection, manuscript preparation, and review. MO: helped in study design/planning, interpretation of results, manuscript preparation, and review. BJL: helped with data interpretation, manuscript preparation, and review. PKS: helped in study design/planning, interpretation of results, manuscript preparation, and review. MK: study design/planning, interpretation of results, manuscript preparation and review, and guarantor.
Funding Research reported in this publication was supported by the National Center for Advancing Translational Science of the National Institute of Health Under Award Number UL1TR002384, the Department of Anesthesiology, Critical Care & Pain Management Research and Education Fund, and the Adult Reconstruction and Joint Replacement Marmor Award at Hospital for Special Surgery (HSS). MK was also supported by the HSS Department of Anesthesiology Young Investigator Award.
Competing interests AS is supported by the C.V. Starr Foundation and is an unpaid consultant on a cannabis research study grant funded by Colombia Cientifica/Colciencias awarded to Pontifical Xavierian University.
Provenance and peer review Not commissioned; externally peer reviewed.