The proper control of acute and chronic pain is one of the most important areas in health care. Despite the profound advances in neuroscience over the past 20 years, we still largely use opiate narcotics, much as was done in the Civil War. Total knee arthroplasty (TKA) is one of the most common orthopedic procedures performed. While knee pain is often a complaint that precedes TKA, the procedure itself is associated with considerable post-operative pain lasting days to weeks, and adequate postoperative pain control is an important factor in determining recovery time and hospital length of stay. Primary methods used to manage post-operative pain involve systemic opioid drugs, and regional blocks. Despite these strategies, patients still report considerable post-operative pain, and often struggle to complete post-operative physical therapy regimens. Additionally, systemic opioid analgesics have associated side-effects that can lead to post-operative complications including but not limited to mental-clouding, confusion, addiction (in some cases), respiratory depression, interactions with other medications, and fatigue. These are not trivial concerns as the population receiving TKA are more and more likely to be elderly and/or overweight and thus these complications can have serious negative consequences. New analgesic strategies are needed that can be used adjunctively to existing strategies with the potential to reduce reliance on opioid analgesia. Several novel brain stimulation technologies including transcranial direct current stimulation (tDCS) are beginning to demonstrate promise as treatments for a variety of pain conditions. Electricity has no metabolite or other residue, and can be delivered with minimal discomfort and without problems associated with drug-drug interactions. In two preliminary studies, the investigators have found that tDCS can reduce post-operative PCA use by as much as 46% in TKA patients while simultaneously reducing subjective pain ratings. These findings are promising, but this new technology is in its infancy, and a foundation of well-controlled, high-quality clinical trials needs to be established before this field moves forward. The proposed study will be the first randomized, double-blind, sham-controlled clinical trial of the effects of tDCS on subjective pain-ratings, PCA opioid usage, and post- operative complications among patients receiving unilateral TKA surgery. Further, this study will examine the relative efficacy of different analgesic electrode placement strategies compared to sham stimulation as well as examine the effects of pain-targeted tDCS compared to an active-sham strategy wherein real brain stimulation will be delivered, but over areas of the brain that should be unrelated to pain experience (thereby determining whether there is any tDCS targeting specificity). Data from this trial will likely yield information regarding the feasibility and effiacy of tDCS as a post-operative pain-management approach. If the proposed pilot trial suggests significant and meaningful effects of tDCS as an adjunctive post-operative pain management strategy, this could change the way post-operative pain management is approached in the future. PUBLIC HEALTH RELEVANCE: The proper control of acute and chronic pain is one of the most important areas in health care. Several brain stimulation technologies including transcranial direct current stimulation (tDCS) are beginning to demonstrate promise as treatments for a variety of pain conditions. This study will be the first randomized, double-blind, controlled study of tDCS technology as an adjunctive pain management strategy for post- operative pain. !