Influence of Patient Sex on Pain Control and Multimodal Analgesia in Total Knee Arthroplasty

The overall goal of this study is to better understand the influence of patient-sex on postoperative pain perception in men versus women following total knee arthroplasty (TKA) utilizing two different multimodal analgesia regimens. Pregabalin is a neuromuscular antagonist of voltage gated calcium channels at the post-synaptic dorsal horns in the spinal cord and brain. It binds to the alpha-2-delta subunit and interrupts pain signal transmission. The use of pregabalin as part of multimodal pain control has been associated with a decrease in postoperative opioid use. This will be a randomized, single-blinded control trial in which patients either will or will not receive pregabalin as part of their multimodal analgesia regimen following TKA. It will be performed at a single institution, with multiple tertiary academic centers. Patients will first be grouped according to their sex, then randomized into one of two arms: 1. Multimodal analgesia regimen including pregabalin; 2. Multimodal analgesia regimen not including pregabalin. For the intervention group, patient will be provided with an oral preoperative pregabalin dose of 150mg on the day of surgery. Patient will continue pregabalin 75mg two times a day, for two weeks postoperatively. For both both groups, the operative technique and additional perioperative analgesic modalities will follow a standard protocol. Primary Endpoint: Acute postoperative pain difference (up to 72 hours), measured by 100mm visual analogue scale (VAS) while at rest and mobilization, between males and females and between multimodal analgesic regimens in patients undergoing TKA. Secondary Endpoints: * Pain control measured by 100mm visual analogue scale (VAS) while at rest and mobilization. * Pain control additionally measured by morphine equivalent units (MEq). * Number of postoperative days to opioid cessation. * Pain measured by Knee Injury and Osteoarthritis Outcome Score (KOOS). * Physical function measured by KOOS, physical component summary (PCS-12) of VR-12. * Mental health measured by mental component summary (MCS-12) of VR-12. * Safety will be tracked by adverse reactions reported or observed by investigators. These will be collected via patient communication and review of the medical record. * Additionally, severity of common short-term postoperative complications like nausea, vomiting, dizziness, and sedation will be assessed by 100mm VAS. The study recruitment phase is estimated to last for 6 months. Subject followup is 6 months.