Recovery from Pain and Disability after Surgery

手术后疼痛和残疾的恢复

• 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
• 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

 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（由适用提供）：手术后的慢性疼痛引起了人们的注意，但对患者很重要的手术后，它只是慢性功能障碍的一个方面。其他包括认知和身体功能障碍，对疼痛和运动的恐惧以及冲动性，这与处方阿片类药物滥用的风险有关。这些问题发生在少数患者（10-40％）中，具体取决于结果指标，在全膝关节置换术（TKA）之后。该P01试图解决在理解，预防和治疗手术后慢性疼痛和残疾方面进展的障碍，这是如此基本，以至于它们不能受到孤立作用的个体研究人员的有意义影响。 1）临床前研究和临床研究都是通过在任意时间作为主要结果的功能障碍的点发生率而进行的；我们表明，在单个动物中恢复时间的建模时间的力量增加，并且2）通常在一个域中检查恢复：我们检查了TKA后的几个以患者为中心的结构域及其在动物中的机制。 3）通过未知的机制和正常动物的临床前研究研究，通过术前认知影响（C-A）状态预测手术后的手术后恢复：我们提供了统一，机理和临床上可行的假设，将C-A状态和基因座核心（LC）的功能（LC）起作用，并利用其测试新颖的培训对疗法的恢复速度迅速恢复到TKA后的疗效。在过去的四年中，这组独立资助的研究人员共同努力，共同产生了新的动物模型，开发概念，并证明了解决这些关键障碍的可行性。正如创新的行政和研究核心所支持的那样，整个P01将通过检查中心假设和3个凝聚力，互动目的对该领域产生重大影响： 1。中心假设：LC在手术损伤时的活性是确定疼痛和其他以患者为中心的结构的恢复速度的关键 2。项目1：LC→脊髓信号对于从超敏反应和手术后的残疾中正常恢复至关重 3。项目2：LC→脊髓，向脊柱上部的信号对于从疼痛，冲动性和手术后的分心中恢复至关重 4。项目3：LC补品活动与灾难性的↔乐观风格相互作用，继续解释多个患者领域恢复的新差异，并确定将受益于预防性Gabapentin治疗的患者