Recovery from Pain and Disability after Surgery

项目摘要 手术使大多数患者受益，但对一些人来说，它会导致慢性疼痛和残疾。这是特别 为减轻疼痛和残疾而进行的手术，如全膝关节置换术 （TKA）。TKA术后1 - 2年，10-30%的患者出现中度至重度膝关节疼痛，40%的患者未出现疼痛 最小的临床上重要的功能改善，20%的人不确定或不满意手术。 认知风格，特别是灾难化，是这些不良结果的重要预测因素，但这是如何实现的呢？ 恢复缓慢，是否可以治疗尚不清楚。 在这一领域取得进展的一个关键障碍是对问题的武断和二分法的定义， 在任意时间关注是否存在疼痛或残疾。这忽视了正在进行的复苏 过程本身，并可能误导预测模型和机制和治疗的研究。同样，很少 术后恢复的前瞻性研究整合了以患者为中心的结果。为了弥补这些差距，我们 威尔： 目的1：描述TKA后的动态疼痛体验、活动和认知反应， 确定这些领域的恢复模式 该领域进展的另一个关键障碍是缺乏一个将C-A状态与 减缓了多个以患者为中心的领域的恢复。该P01检验了强直性位点 蓝斑（LC）活动，通过瞳孔测量推断，与认知风格相互作用，沿着一个灾难性的 乐观（C O）持续到对疼痛的感知以及从疼痛、身体残疾中恢复的时间过程， 冲动和执行功能。加巴喷丁，通常用于治疗慢性疼痛，激活动物的LC， 但不能预防普通人群手术后的慢性疼痛。我们认为，这一失败反映了反对 LC活动的行动取决于基线C ParticipO风格，在我们的第二个目标将： 目的2：测试加巴喷丁是否以依赖于其自身的方式改变TKA后的恢复时间进程。 在C Participo维度中与给药前瞳孔直径和偏好风格的相互作用 最后，作为最终测试加巴喷丁应答者是否也可以在 接受高剂量阿片类药物治疗的患者（术后疼痛风险高），我们将： 目的3：测试加巴喷丁是否增加接受TKA的高血压患者的瞳孔直径 术前给予阿片类药物，并检查阿片类药物的使用是否会调节Aim 1中的相关性 该行政补充将允许完成目标1和2的临床试验， 由于不可预见的情况而延迟开始，然后由于疫情而于2020年延迟。没有 适度的补充，试验将无法达到招募设计，以有足够的权力来测试， 潜在的假设

Project Summary Surgery benefits most patients, but for some, it results in chronic pain and disability. This is particularly troubling with a surgery which is performed to alleviate pain and disability, such as total knee arthoplasty (TKA). One-two years after TKA, 10-30% of patients have moderate-severe knee pain, 40% fail to show minimal clinically important improvement for function, and 20% are unsure or dissatisfied with surgery. Cognitive style, especially catastrophizing, is an important predictor of these poor outcomes, but how this slows recovery and whether it can be treated are unknown. A critical barrier to progress in this field is the arbitrary and dichotomous definition of the problem and focus on presence or absence of pain or disability at an arbitrary time. This disregards the ongoing recovery process itself and can mislead predictive models and study of mechanisms and treatment. Similarly, few prospective studies of postoperative recovery integrate patient-centered outcomes. To address these gaps we will: Aim 1: Characterize the dynamic pain experience, activity, and cognitive response after TKA and determine patterns of recovery in these domains Another critical barrier to progress in the field is the lack of a, modifiable hypothesis linking C-A state to slowed recovery across multiple patient-centered domains. This P01 tests the hypothesis that tonic locus coeruleus (LC) activity, inferred by pupillometry, interacts with cognitive style along a catastrophizing ↔ optimism (C↔O) continuum to perception of pain and time course of recovery from pain, physical disability, impulsivity, and executive function. Gabapentin, often used to treat chronic pain, activates the LC in animals, but fails to prevent chronic pain after surgery in a general population. We believe this failure reflects opposing actions of LC activity depending on baseline C↔O style, and in our second aim will: Aim 2: Test whether gabapentin alters time course of recovery after TKA in a manner dependent on its interaction with pre-drug pupil diameter and preferred style in the C↔O dimension Finally, as a first step to eventually test whether gabapentin responders can also be identified in patients on high dose opioids (who are at high risk for pain after surgery) we will: Aim 3: Test whether gabapentin increases pupil diameter in patients undergoing TKA who are on high dose opioids preoperatively and to examine whether opioid use moderates the associations in Aim 1 This administrative supplement will allow completion of the clinical trial for Aims 1 and 2 which was delayed in starting due to unforeseen circumstances and then delayed in 2020 due to the pandemic. Without the modest supplement, the trial will not achieve enrollment as designed to have adequate power to test the underlying hypotheses.