Recovery from Pain and Disability after Surgery

手术后疼痛和残疾的恢复

基本信息

批准号：
9900798
负责人：
James Eisenach
金额：
$ 141.17万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
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/9900798
关键词：
Acute Address Affective Animal Model Animals Attention Biological Brain Stem Caliber Chronic Clinical Clinical Research Clinical Trials Cognitive Data Distress Fright Functional disorder Funding Growth Health Human Hypersensitivity Impulsivity Incidence Individual Intervention Laboratories Link Measures Methods Minority Modeling Movement Nature Neuronal Plasticity Online Systems Operative Surgical Procedures Outcome Outcome Measure Pain Patients Pharmaceutical Preparations Physical Function Postoperative Period Process Pupil Quality of life Rattus Recovery Reporting Research Research Personnel Resolution Risk Risk Factors Signal Transduction Speed Spinal Spinal Cord Surgical Injuries Surgical Models Testing Time Work chronic neuropathic pain chronic pain clinically actionable cognitive function cohesion conditioned pain modulation cost disability distraction gabapentin healing improved inhibitor/antagonist innovation interactive tool knee pain knee replacement arthroplasty locus ceruleus structure monoamine motivated behavior neglect new therapeutic target noradrenergic novel opioid misuse optimism patient oriented physically handicapped postoperative recovery pre-clinical pre-clinical research prescription opioid misuse prevent primary outcome protective effect public health priorities public health relevance research study response reuptake therapy design

项目摘要

DESCRIPTION (provided by applicant): Chronic pain after surgery has garnered considerable attention, but it is but one facet of chronic dysfunction after surgery important to patients. Othes include cognitive and physical dysfunction, fear of pain and movement, and impulsivity, which is tied to risk of prescription opioid misuse. These problems occur in a large minority of patients (10-40%), depending on the outcome measure, after total knee arthroplasty (TKA). This P01 seeks to address barriers to progress in understanding, preventing, and treating chronic pain and disability after surgery which are so fundamental that they cannot be meaningfully impacted by individual investigators acting in isolation. 1) Both preclinical and clinical research is stymid by use of point incidences of dysfunction at arbitrary times as primary outcomes; we show the increased power of modeling time course of recovery in individual animals and humans after surgery and its utility to examine interventions and mechanisms. 2) Recovery is typically examined in one domain: we examine several patient-centered domains after TKA and their mechanisms in animals. 3) Recovery after surgery in patients is predicted by preoperative cognitive-affective (C-A) state by unknown mechanisms and preclinical research studies recovery in normal animals only: we provide a unifying, mechanistic, and clinically actionable hypothesis relating C-A state and locus coeruleus (LC) function and use it to test novel targeting of therapies to speed recovery after TKA. Over the past 4 years this group of independently funded investigators has worked together to generate new animal models, develop concepts, and demonstrate feasibility of addressing each of these critical barriers. As supported by innovative Administrative and Research Cores, this P01 as a whole will have a major impact in the field by examining a central hypothesis and 3 cohesive, interactive aims: 1. CENTRAL HYPOTHESIS: Activity of the LC at the time of and in response to surgical injury is a key determinant of speed of recovery across pain and other patient-centered domains 2. PROJECT 1: LC → spinal cord signaling is essential to normal recovery from hypersensitivity and disability after surgery and is disrupted by experimentally induced increased tonic LC activity 3. PROJECT 2: LC → spinal cord, signaling to supraspinal regions is essential to recovery from pain, impulsivity, and distraction after surgery and is disturbed by pre-surgery increased tonic LC activity 4. PROJECT 3: LC tonic activity interacts with a catastrophizing ↔ optimism cognitive style continuum to explain novel variance in time course of recovery across multiple patient domains and identifies patients who will benefit from or be harmed by preventative gabapentin treatment

描述（由申请人提供）：手术后的慢性疼痛已经引起了相当多的关注，但这只是手术后慢性功能障碍的一个方面，对患者来说很重要，其他方面包括认知和身体功能障碍、对疼痛和运动的恐惧以及与此相关的冲动。处方阿片类药物滥用的风险取决于全膝关节置换术 (TKA) 后的结果测量，这些问题发生在极少数患者 (10-40%) 中。在理解、预防和治疗手术后慢性疼痛和残疾方面取得的进展是如此重要，以至于单独的研究者无法对它们产生有意义的影响 1) 临床前和临床研究都因使用任意时间的功能障碍点发生率而受到阻碍。作为主要结果；我们展示了对个体动物和人类手术后恢复时间过程进行建模的能力增强，及其在检查干预措施和机制方面的实用性 2) 通常在一个领域检查恢复：我们在 TKA 后检查几个以患者为中心的领域。及其在动物中的作用机制。 3) 患者手术后的恢复是通过未知机制的术前认知情感 (C-A) 状态来预测的，并且临床前研究仅研究正常动物的恢复：我们提供了一个与 C-A 状态和蓝斑 (LC) 相关的统一、机制和临床可操作的假设）功能并用它来测试新的靶向疗法，以加速 TKA 后的恢复。在过去 4 年里，这组独立资助的研究人员共同努力生成新的动物模型，开发概念，并证明解决每个问题的可行性。在创新管理和研究核心的支持下，本 P01 作为一个整体将通过研究一个中心假设和 3 个有凝聚力的互动目标对该领域产生重大影响： 1. 中心假设：手术损伤时和手术损伤后 LC 的活动是疼痛和其他以患者为中心的领域恢复速度的关键决定因素 2. 项目 1：LC → 脊髓信号传导对于手术后从超敏反应和残疾中正常恢复至关重要，并且会被实验诱导的强直性 LC 活性增加所破坏 3. 项目 2：LC → 脊髓，向脊髓上区域发出信号对于手术后疼痛、冲动和分心的恢复至关重要，并且会受到术前强直性 LC 活性增加的干扰 4. 项目 3：LC 补药活动与灾难性 ↔ 乐观认知风格连续体相互作用，解释多个患者领域恢复时间过程中的新差异，并确定将从预防性加巴喷丁治疗中受益或受到伤害的患者