What are the main risk factors that predict chronic pain after total knee replacement?

1. The scale of the problem and how chronic pain is defined

Chronic postsurgical pain after TKA is commonly defined as pain that persists and is bothersome at least three to six months after surgery, and prevalence estimates cluster around 10–30% depending on outcome measures and follow‑up, with many reviews citing roughly 20% as a typical figure ^{[1] [4] [5]}.

2. Psychological risk factors are consistently among the strongest predictors

Meta-analyses and systematic reviews identify catastrophizing (tendency to magnify or ruminate about pain) and poor preoperative mental health as leading independent predictors of persistent pain after TKA, and these psychological variables show up across multivariable studies as stronger and more consistent predictors than many biomedical measures ^{[2] [6] [7]}.

3. Pain before and immediately after surgery is a dominant clinical predictor

Higher preoperative knee pain intensity, pain at other body sites, and severe acute postoperative pain (within days to weeks after surgery) all predict chronic pain months later; several longitudinal cohorts and meta-analyses emphasize that both baseline pain burden and early postoperative pain trajectories are key signals of risk ^{[6] [7] [4]}.

4. Pain distribution and central sensitization matter beyond the joint

Patients reporting pain at multiple sites or widespread sensitization (reduced conditioned pain modulation, altered pain thresholds) are at higher risk of persistent pain after TKA, suggesting that central nervous system factors and pain processing phenotypes—not just joint pathology—contribute to poor pain outcomes ^{[8] [9] [4]}.

5. Demographics, comorbidity, and biology: contributory but inconsistent

Age, BMI, and comorbidities (for example diabetes or hypertension) appear in some studies as predictors—older age and obesity have been associated with higher CPSP in specific cohorts—but their effects are less consistent across pooled analyses than psychosocial and pain-related predictors; genetics and inflammatory or neurophysiologic markers show promising signals but require more rigorous evidence ^{[10] [5] [7]}.

6. Surgical, perioperative and health‑system factors explain only part of the risk

Large registry analyses find that postoperative complications, early recovery patterns, and certain operation-related variables are associated with chronic pain but that models including these factors have only fair discriminative ability (c‑statistic ≈0.7), indicating that surgery‑related variables alone cannot reliably predict which patients will develop chronic pain ^{[3] [11]}.

7. Modifiable targets, interventions, and the limits of current evidence

Systematic reviews flag preoperative interventions (psychological therapies, prehabilitation) as plausible strategies because psychosocial and pain variables are modifiable, but randomized trial evidence that treating these preoperative risk factors reduces long‑term CPSP after TKA remains limited and inconclusive; authors call for trials that target high‑risk phenotypes identified by pain and psychological profiling ^{[2] [12] [11]}.

8. Gaps, uncertainty and where research is headed

Despite dozens of observational studies and several meta‑analyses, heterogeneity in outcome measures, variable follow‑up intervals, and inconsistent assessment of central sensitization, genetics, and postoperative pain trajectories mean the relative contribution of each risk domain remains incompletely quantified; experts repeatedly call for rigorously conducted prospective cohorts and targeted intervention trials to move from association to prevention ^{[7] [9] [5]}.

Conclusion

Clinically actionable risk assessment should prioritize psychological screening (catastrophizing, mental health), measurement of preoperative and early postoperative pain intensity and distribution, and recognition of multisite or sensitized pain phenotypes, while acknowledging that demographic and surgical factors also play roles; however, current evidence supports the idea that focusing on modifiable psychosocial and perioperative pain factors offers the best immediate opportunity to reduce chronic pain after TKA, even as definitive trial data are still needed ^{[2] [6] [3]}.