Transcranial Direct Current Stimulation in the Management of Post-operative Pain

描述（由申请人提供）：急性和慢性疼痛的适当控制是医疗保健中最重要的领域之一。尽管在过去的20年里，神经科学取得了巨大的进步，但我们仍然在很大程度上使用阿片类麻醉剂，就像内战时期一样。全膝关节置换术（TKA）是最常见的骨科手术之一。虽然膝关节疼痛通常是TKA之前的主诉，但手术本身与持续数天至数周的相当大的术后疼痛相关，充分的术后疼痛控制是决定恢复时间和住院时间的重要因素。用于管理术后疼痛的主要方法包括全身性阿片类药物和区域阻滞。尽管有这些策略，患者仍然报告相当大的术后疼痛，并且经常 努力完成术后物理治疗方案。此外，全身性阿片类镇痛药具有相关的副作用，可导致术后并发症，包括但不限于精神模糊、意识模糊、成瘾（在某些情况下）、呼吸抑制、与其他药物的相互作用和疲劳。这些都不是微不足道的问题，因为接受TKA的人群越来越有可能是老年人和/或超重，因此这些并发症可能会产生严重的负面后果。需要新的镇痛策略，可以替代现有的策略，有可能减少对阿片类镇痛的依赖。包括经颅直流电刺激（tDCS）在内的几种新型脑刺激技术开始显示出治疗各种疼痛状况的前景。电没有代谢物或其他残留物，可以在最小的不适和没有与药物相互作用相关的问题的情况下输送。在两项初步研究中，研究人员发现tDCS可以减少TKA患者术后PCA的使用高达46%，同时降低主观疼痛评分。这些发现是有希望的，但这项新技术还处于起步阶段，在该领域向前发展之前，需要建立一个良好控制的高质量临床试验的基础。拟议的研究将是首次在接受单侧TKA手术的患者中进行的tDCS对主观疼痛评级、PCA阿片类药物使用和术后并发症影响的随机、双盲、假对照临床试验。此外，本研究将检查不同镇痛电极放置策略与假刺激相比的相对疗效，并检查疼痛靶向tDCS与主动假刺激策略相比的效果，其中将递送真实的脑刺激，但在与疼痛体验无关的脑区域上（从而确定是否存在任何tDCS靶向特异性）。本试验的数据可能会产生关于tDCS作为术后疼痛管理方法的可行性和有效性的信息。如果拟议的试点试验表明tDCS作为一种持续的术后疼痛管理策略具有显著和有意义的效果，这可能会改变未来的术后疼痛管理方式。

DESCRIPTION (provided by applicant): 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.