Personalized Perioperative Medicine: Translational Studies in the Prevention of Postoperative Pain and Opioid Misuse

个性化围手术期医学：预防术后疼痛和阿片类药物滥用的转化研究

• 批准号: 9769076
• 负责人: KRISTIN SCHREIBER
• 金额: $ 42.48万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9769076
• 关键词: Acute; Anguish; Area; Caring; Chronic; Esthesia; Event; Exposure to; Healthcare; Human; Individual; Injury; Longevity; Longitudinal Studies; Measures; Medical; Mental Processes; Minority; Molecular; Nervous system structure; Neurosciences; Operative Surgical Procedures; Opioid; Pain; Patient Care; Patients; Perioperative; Phenotype; Physical Sufferings; Postoperative Pain; Postoperative Period; Predisposition; Prevention; Preventive; Preventive therapy; Preventive treatment; Psychophysics; Psychosocial Assessment and Care; Questionnaires; Research; Risk; Risk Factors; Sensory; Severities; Site; Sleep disturbances; Speed; Standardization; Stimulus; Stress; System; Testing; Training; Translating; Variant; addiction; base; chronic pain; clinically significant; cost; disability; experience; high risk; human model; improved; non-opioid analgesic; novel; opioid misuse; opioid use; pain model; pain perception; pain reduction; personalized medicine; pre-clinical research; prevent; programs; psychosocial; response; success; translational medicine; translational study

PROJECT SUMMARY Surgery is an increasingly common event, impacting over 230 million people annually. Post-surgical pain is variable in severity and duration, but a significant minority (20-30%) of patients experience surgical site pain lasting a year or longer. Such persistent postsurgical pain causes physical and mental suffering and disability, and long exposure to postoperative opioids also puts patients at risk of misuse and addiction. Despite excellent preclinical research into the molecular events involved in the transition of acute to chronic pain after injury, little success at translating these findings to actual prevention of persistent postoperative pain in human patients has been realized. My research program has focused on building a working human model of this transition, by systematic and longitudinal study of pain before, during and after a variety of surgeries. Importantly, we have focused our efforts to identify risk factors to predict those who will actually develop chronic postsurgical pain, rather than those who won’t (70-80%), to make study of this problem more efficient. A crucially important factor in determining the trajectory of post-surgical pain appears to be the capacity for amplification in the circuitry of the pain system, whereby incoming painful input may be increased to the point of intense discomfort. This amplification may be protective in the short term, but dysfunctional if it is excessive or persistent. In our psychophysics lab, we study measures that indicate an excessive (temporal summation of pain, TSP) or prolonged response (painful after sensations, PAS) amplification response of the nervous system in response to standardized pain stimuli. Amplification can also occur at a psychosocial level, where stress, sleep disruption, and catastrophizing (a mental process by which rumination, magnification, and worry increase salience and importance) increase pain perception. Importantly. TSP, PAS, stress, sleep disturbance and catastrophizing are much more prominent in some individuals, and account for a sizeable amount of the variation in postsurgical pain severity (and far more than the surgical extent). We have adapted these tests to easily and non-invasively test this “amplification phenotype” in individuals BEFORE they have surgery, using modified bedside quantitative sensory tests (QSTs), and brief, validated questionnaires. We propose to use these measures of preoperative amplification phenotype, in order to help target both known and novel non-opioid preventive treatments to those individuals who need them most. This is my area of expertise, as I am an anesthesiologist with formal training in pain neuroscience, psychophysical and psychosocial assessment, and practical experience in conducting translational studies in post-surgical pain. Broadly, my research plan will use this human translational pain model: 1) to speed testing of pain preventive therapies, 2) to develop strategies to reduce pain and opioid use after surgery in high risk individuals, and 3) to forward personalized medicine in the perioperative period. Providing precision medical care and preventing chronic postsurgical pain and opioid use will ultimately improve health care for patients, and lower its cost.

项目摘要 手术是一个越来越常见的事件，每年影响超过2.3亿人。术后 疼痛的严重程度和持续时间各不相同，但极少数（20 - 30%）患者的手术部位 疼痛持续一年或更长时间。这种持续的术后疼痛会导致身体和精神上的痛苦， 残疾和长期暴露于术后阿片类药物也使患者面临滥用和成瘾的风险。 尽管对参与急性向慢性转化的分子事件进行了出色的临床前研究， 损伤后疼痛，将这些发现转化为实际预防持续性术后疼痛的成功率很低 在人类患者中已经实现。我的研究项目集中在建立一个工作的人类模型， 通过对各种手术前、手术中和手术后疼痛的系统和纵向研究， 重要的是，我们已经集中精力确定风险因素，以预测那些实际上会发展的人。 慢性术后疼痛，而不是那些谁不会（70 - 80%），使研究这个问题更有效。 决定术后疼痛轨迹的一个至关重要的因素似乎是 用于在疼痛系统的电路中放大，由此传入的疼痛输入可以增加到 强烈不适的点。这种放大在短期内可能是保护性的，但如果它是功能失调的， 过度的或持久的。在我们的心理物理学实验室，我们研究的措施，表明过度（时间） 疼痛总和，TSP）或延长的反应（感觉后疼痛，PAS）的放大反应， 神经系统对标准化疼痛刺激的反应。放大也可以发生在心理社会层面， 压力、睡眠中断和灾难化（一种心理过程，通过这种心理过程， 担心增加显著性和重要性）增加疼痛感知。重要的是。TSP、PAS、压力、睡眠 干扰和灾难化在某些个体中更为突出，并占相当大的比例。 术后疼痛严重程度的变化量（远远超过手术范围）。我们已经适应 这些测试，以方便和非侵入性测试这种"扩增表型"在个人之前，他们有 手术，使用改良的床边定量感觉测试（QST）和简短的，有效的问卷调查。 我们建议使用这些术前扩增表型的措施，以帮助靶向 已知的和新的非阿片类药物预防性治疗给那些最需要它们的人。这是我 专业领域，因为我是一名麻醉师，在疼痛神经科学，心理物理和 心理社会评估，并在进行手术后疼痛的转化研究的实践经验。 概括地说，我的研究计划将使用这种人类翻译疼痛模型：1）加速疼痛预防剂的测试 治疗，2）制定策略以减少高风险个体手术后的疼痛和阿片类药物使用，以及3） 推进围手术期个体化用药。提供精准医疗和预防 慢性术后疼痛和阿片类药物的使用将最终改善患者的医疗保健，并降低其成本。