A biomarkers assessments 5 years after total knee replacement in osteoarthritis patients with and without chronic postoperative pain

Background and aims: Knee osteoarthritis (KOA) is prevalent in the general population and total knee replacement (TKR) is the end-stage treatment. Approximately 20% of patients experience chronic postoperative pain after TKR. Studies have explored the inflammatory response before and after TKR, but it is still unclear if inflammation biomarkers can be associated with long-term chronic postoperative pain. The current study aimed to evaluate a multiplex subset of inflammatory mediators in patients 5 years after surgery and study potential correlations to clinical pain in patients with and without postoperative pain.

Methods: Plasma samples were collected 5 years after surgery from 82 patients. Samples were analyzed using Human-XL-Cytokine Magnetic-44-plex Luminex®-assay. Pain in the last 24 hours was assessed using VAS scale. Patients were categorized as experiencing chronic postoperative pain if postoperative VAS was higher than 3/10, otherwise the patients were categorized as recovered and pain free. Biomarker expressions were compared between the two groups.

Results: Sixty-one patients were categorized with chronic postoperative pain and 21 patients were categorized as pain free. T-test highlighted 5 significant proteins (IFN-g, IL-4, MIP-3a, TGF-β, VEGF) comparing the groups (p<0,05). Correlations showed 11 markers associated with pain intensity (p<0,05). Regression models explained 23% of pain and demonstrated VEGF as independent factor for postoperative pain (p<0,05).

Conclusions: The present study confirms a low-grade inflammation in a subset of patients with continues postoperative pain five years after TKR. The current results provide insights into the understanding of the underlying mechanisms which may drive the long experience of the pain after TKA surgery.