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Sex matters: central sensitization and opioid use after total knee arthroplasty

Knee. 2026 Mar 19;61:104426. doi: 10.1016/j.knee.2026.104426. Online ahead of print.

ABSTRACT

BACKGROUND: Total knee arthroplasty (TKA) is a prevalent orthopaedic procedure often accompanied by significant postoperative pain. Central sensitization, marked by increased nervous system reactivity, may influence opioid consumption variability after TKA. Investigating central sensitization, particularly regarding sex differences, could enhance postoperative care and opioid prescribing practices for TKA patients.

METHODS: Patients scheduled for TKA were assessed preoperatively and at 2 and 6 weeks postoperatively. Data collected included demographics, PROMIS-29, Brief Pain Inventory (BPI), Pain Catastrophizing Scale, Central Sensitization Inventory (CSI), and quantitative sensory testing. Participants recorded opioid use in home diaries over 6 weeks, measured in morphine milligram equivalents (MME) and days of use. Analyses involved descriptive statistics, sex differences, correlations, and regression models.

RESULTS: Thirty-nine participants (59% females) were enrolled. CSI scores indicated sub-clinical central sensitization in a majority of patients. No sex differences were observed in patient-reported outcomes, but males consumed significantly more opioids than females (median MME: 248 vs 519, p = 0.023), with similar durations of use (median days: 18 vs 16, p = 0.50). Pain levels correlated with opioid use duration (rs = 0.50, p = 0.001), stronger in males (rs = 0.69) than females (rs = 0.33). Central sensitization correlated with opioid use duration in males (rs = 0.81, p < 0.001), unlike females (rs = -0.11, p = 0.64).

CONCLUSION: Central sensitization significantly impacts opioid use in males post-TKA, challenging existing beliefs. Males with preoperative CSI scores indicating central sensitization showed sustained opioid use above norms, suggesting CSI as a predictive tool for postoperative opioid consumption. Recognizing sex-specific differences in central sensitization could improve pain management and opioid prescribing in TKA.

PMID:41863198 | DOI:10.1016/j.knee.2026.104426

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