Background: Unexplained postoperative pain is one of the most feared complications of total knee arthroplasty (TKA). A persistent noxious peripheral stimulus, such as the pain of chronic knee osteoarthritis, can cause central sensitization in which the central nervous system becomes hyperexcitable, resulting in hypersensitivity to both noxious and non-noxious stimuli. Patients with central sensitization may be more susceptible to unexplained pain after TKA. Duloxetine, a selective serotonin norepinephrine reuptake inhibitor (SNRI), can ameliorate the pain associated with central sensitization, and we aimed to determine whether it could reduce postoperative pain and improve quality of recovery after TKA in patients with central sensitization. Methods: Patients undergoing TKA were screened for central sensitization preoperatively with use of the Central Sensitization Inventory (CSI). Among 464 patients with primary osteoarthritis who were scheduled for primary unilateral TKA, 80 were identified as being centrally sensitized and were included in the study. Forty patients were randomly assigned to the duloxetine group (30 mg 1 day before surgery and for 6 weeks after surgery), and 40 were randomized to the control group (no duloxetine). Pain and quality of recovery were assessed with use of the Brief Pain Inventory (BPI), the Short Form-36 (SF-36), the Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP), and the Hamilton Depression Scale. The prevalence of adverse medication effects was also noted. Results: The patients in the duloxetine group had better performance across pain metrics during the initial 2 to 12-week postoperative period (p < 0.05). The duloxetine group also had a superior quality of recovery 2 weeks after TKA, as indicated by emotional and physical functioning (all p < 0.05). There was no difference between groups in the prevalence of adverse events. Conclusions: A substantial number of patients are centrally sensitized before TKA. Surgeons should consider selective incorporation of duloxetine into the multimodal postoperative analgesic protocol, according to the severity of central sensitization, to minimize the possibility of persistent pain following TKA. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Therapeutic study, Level I.

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