Recovery from Pain and Disability after Surgery

手术后疼痛和残疾的恢复

• 批准号: 10360703
• 负责人: James Eisenach
• 金额: $ 15.65万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10360703
• 关键词: Address; Administrative Supplement; Animals; Caliber; Clinical; Clinical Research; Clinical Trials; Cognitive; Dimensions; Dose; Enrollment; Failure; General Population; Impulsivity; Knee; Link; Operative Surgical Procedures; Opioid; Outcome; Pain; Patient-Focused Outcomes; Patients; Pattern; Persistent pain; Pharmaceutical Preparations; Pharmacotherapy; Postoperative Pain; Process; Prospective Studies; Pupil; Recovery; Testing; Time; chronic pain; design; disability; executive function; experience; functional improvement; gabapentin; high risk; knee pain; locus ceruleus structure; opioid use; optimism; pain perception; pandemic disease; patient oriented; physically handicapped; postoperative recovery; predictive modeling; prevent; response

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.

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。这是特别的 困扰于为减轻疼痛和残疾而进行的手术，如全膝关节成形术 (TKA)。全膝关节置换术后1-2年，10-30%的患者出现中重度膝关节疼痛，40%的患者没有表现出 临床上重要的功能改善微乎其微，20%的人对手术不确定或不满意。 认知方式，尤其是灾难性的，是这些糟糕结果的一个重要预测因素，但这是如何 它会减缓康复，是否可以治疗，目前尚不清楚。 在这一领域取得进展的一个关键障碍是对问题和 专注于在任意时间有无疼痛或残疾。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，几乎没有人 术后恢复的前瞻性研究综合了以患者为中心的结果。为了解决这些差距，我们 将： 目的1：描述TKA术后的动态疼痛体验、活动和认知反应。 确定这些领域的恢复模式 该领域取得进展的另一个关键障碍是缺乏将C-A状态与 在多个以患者为中心的领域中减缓了恢复。这个P01检验了紧张素轨迹的假说 通过斜视测量法推断的蓝斑(LC)活动与认知方式沿着灾难性的↔相互作用 乐观主义(C↔O)对疼痛感知和从疼痛中恢复的时间进程、身体残疾、 冲动和执行功能。加巴喷丁通常用于治疗慢性疼痛，它激活动物的LC， 但未能在普通人群中预防手术后的慢性疼痛。我们认为，这一失败反映了 LC活动的行动取决于基线C↔O风格，在我们的第二个目标中将： 目的2：测试加巴喷丁是否以一种依赖于其的方式改变TKA术后恢复时间 C-↔-O维度与用药前瞳孔直径和偏爱类型的交互作用 最后，作为最终测试加巴喷丁应答者是否也可以在 服用大剂量阿片类药物的患者(手术后疼痛风险高)，我们将： 目的3：测试加巴喷丁是否增加了高眼压下TKA患者的瞳孔直径 术前服用阿片类药物，并检查阿片类药物的使用是否缓和了目标1中的关联 这一行政补充将允许完成AIMS 1和AIMS 2的临床试验 由于不可预见的情况而推迟启动，然后由于大流行而推迟到2020年。如果没有 在适度补充的情况下，该试验将不会像设计的那样实现招生，以有足够的能力测试 潜在的假设。