The well-aligned yet painful total knee arthroplasty: a timeline-based diagnostic approach to persistent postoperative pain

Persistent pain following technically successful total knee arthroplasty (TKA) affects 10–20% of patients despite satisfactory implant alignment and stability. Conventional diagnostic algorithms predominantly emphasize structural pathology while often under-recognizing extra-articular and centralized pain mechanisms, contributing to delayed diagnosis and unnecessary revision surgery. This narrative review was conducted in accordance with the Scale for the Assessment of Narrative Review Articles (SANRA). PubMed, Embase and the Cochrane Library were searched from database inception to June 2026 for studies addressing persistent pain after primary TKA. Evidence was synthesized across four domains: intra-articular pathology, extra-articular/referred causes, centralized and psychosocial pain mechanisms, and existing diagnostic algorithms. Based on the available literature, a timeline-stratified diagnostic framework was developed. Persistent pain after well-aligned TKA arises from three principal mechanistic categories: intra-articular, extra-articular/referred, and centralized pain. The differential diagnosis evolves with postoperative timing, with structural complications predominating early, instability and patellofemoral disorders emerging during intermediate follow-up, and aseptic loosening alongside centralized pain becoming increasingly relevant later. The proposed algorithm prioritizes systematic exclusion of infection, targeted assessment of mechanical pathology, evaluation of hip, spine and hindfoot disorders, and mandatory screening for central sensitization and neuropathic pain before considering revision surgery. Persistent pain following well-aligned TKA is multifactorial and requires a structured, timeline-based diagnostic strategy that integrates structural, extra-articular and centralized pain mechanisms. This comprehensive approach may facilitate earlier diagnosis, reduce unnecessary investigations and revision procedures, and support more individualized management while providing a practical framework for future prospective validation.