Impaired Conditioned Pain Modulation and Peripheral Sensitization in Chronic Postsurgical Pain After Total Knee Arthroplasty

OBJECTIVES: Chronic postsurgical pain (CPSP) is a common complication following total knee arthroplasty (TKA), affecting up to 30% of patients. Altered nociceptive processing may underlie CPSP mechanisms. The study aimed to compare conditioned pain modulation (CPM), local and widespread sensitization between patients with and without CPSP. METHODS: A prospective case-control study was conducted among 117 patients undergoing TKA due to primary knee osteoarthritis. Participants were classified as CPSP or non-CPSP based on pain intensity (≥30 mm on the visual analog scale) at 3 months postoperatively. Quantitative sensory testing assessed CPM, local pressure pain thresholds (PPTs), and remote PPTs at tibial and forearm locations. Measures were taken at 3 and 6 months after surgery. Group comparisons and linear mixed-effects models were applied. RESULTS: Patients with CPSP (n=53) exhibited significantly lower CPM responses at both local and remote sites compared to non-CPSP patients (n=64), with differences persisting over time. Local PPTs were significantly reduced in the CPSP group across all periarticular sites, suggesting enhanced peripheral sensitization. At remote locations, lower PPTs were observed at both tibiae and at the ipsilateral forearm at 3 months; at 6 months, group differences were restricted to the ipsilateral tibia, indicating spatially selective alterations in pain modulation rather than generalized hypersensitivity. DISCUSSION: CPSP following TKA is associated with persistent differences in descending pain inhibition and increased local pressure sensitivity. These findings suggest that persistent dysfunction in descending inhibitory pathways and localized peripheral sensitization are associated with pain persistence beyond the expected healing period.