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: 10362272
• 负责人: KRISTIN SCHREIBER
• 金额: $ 1.15万
• 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/10362272
• 关键词: Accident and Emergency department; Acute; Acute Pain; Adult; Affect; Age; American; Anguish; Area; Biomedical Research; Caring; Categories; Cessation of life; Chronic; Clinical Research; Collection; Communities; Development; Diabetes Mellitus; Disadvantaged; Doctor of Philosophy; Ensure; Environment; Esthesia; Evaluation; Event; Exposure to; Funding; Gender; Goals; Grant; Healthcare; Healthcare Systems; Heart Diseases; Human; Individual; Injury; International; Intervention; Lead; Life Expectancy; Longevity; Longitudinal Studies; Malignant Neoplasms; Measures; Medical; Mentorship; Minority; Molecular; Moods; Names; Nervous system structure; Neuraxis; Neuronal Plasticity; Neurosciences; Operating Rooms; Operative Surgical Procedures; Opiate Addiction; Opioid; Outcome; Pain; Pain Research; Parents; Patients; Pattern; Perioperative; Peripheral; Persistent pain; Phenotype; Physical Sufferings; Physiological; Population; Postdoctoral Fellow; Postoperative Pain; Postoperative Period; Predisposition; Prevention; Preventive; Preventive therapy; Preventive treatment; Problem Solving; Psychologist; Psychophysics; Publications; Questionnaires; Research; Risk; Risk Factors; Self Administration; Sensory; Severities; Site; Sleep; Sleep disturbances; Speed; Standardization; Stimulus; Stress; Stretching; Structure; Surgical Injuries; System; Testing; Time; Training; Translating; United States National Institutes of Health; Variant; addiction; base; career; chronic pain; climate change; clinical care; clinically significant; cost; cost effective; disability; disability impact; experience; flexibility; functional disability; high risk; human model; improved; intersectionality; non-opioid analgesic; novel; opioid misuse; opioid use; pain model; pain perception; pain reduction; parent project; personalized intervention; personalized medicine; pre-clinical research; predictive modeling; prevent; programs; psychosocial; response; scale up; societal costs; success; translational medicine; translational study

ABSTRACT 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. Our 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. An 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. 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 increases pain perception. These factors are much more prominent in some individuals, and account for a sizeable amount of the variation in postsurgical pain severity. 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 and 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. The research team is led by an anesthesiologist with formal training in pain neuroscience and includes a PhD Psychologist coinvestigator. We have a strong track record of successfully launching postdoctoral fellows into their own independent research careers. Inclusion of Mr. Overstreet on our team will allow him needed training, mentorship, exposure to a new research area, and opportunities for publication. Together the team will have a more diverse approach to understanding the development of persistent pain using 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 all patients.

抽象的 手术是一个日益普遍的事件，每年影响超过2.3亿人。外科手术 疼痛的严重程度和持续时间是可变的，但是很大的少数患者（20-30％）经历了手术部位 疼痛持续一年或更长时间。这种持续性术后疼痛会导致身体和精神痛苦，并且 残疾和术后阿片类药物的长期暴露也使患者面临小姐和成瘾的风险。 尽管对急性向慢性过渡涉及的分子事件进行了出色的临床前研究 受伤后的疼痛，将这些发现转化为实际预防持续性术后疼痛的疼痛几乎没有成功 在人类患者中，已经实现了。我们的研究计划的重点是建立一个有效的人类模型 在这种过渡过程中，通过对各种手术前后的疼痛进行系统和纵向研究。 重要的是，我们集中精力确定风险因素，以预测那些会真正发展的人 慢性术后疼痛，而不是那些不会（70-80％）的疼痛，以使研究这个问题更有效。 确定后手术后疼痛轨迹的重要因素似乎是 疼痛系统电路的放大，从而增加疼痛的输入可能会增加到该点 激烈的不适。在我们的心理物理学实验室中，我们研究表明过多的措施（时间 疼痛，TSP）或长时间反应（感觉后的疼痛，PAS）的扩增反应 神经系统响应标准化疼痛刺激。放大也可以在社会心理水平上发生， 在压力，睡眠中断和灾难性的地方会增加疼痛感知。这些因素更多 在某些人中很突出，并说明了术后疼痛严重程度的大量变化。 我们已经对这些测试进行了调整，以轻松，非侵入性测试个体中的“扩增表型” 在进行手术之前，使用改良的床边定量感觉测试和经过验证的问卷。 我们建议使用这些术前扩增表型的度量，以帮助目标 已知和新颖的非阿片类药物预防性治疗给那些最需要这些的人。这 研究团队由麻醉师领导，并接受了疼痛神经科学的正规培训，并包括博士学位 心理学家共同评估者。我们有成功将博士后研究员推入的良好记录 他们自己的独立研究职业。将Overstreet先生纳入我们的团队将允许他需要 培训，精神训练，对新研究领域的接触以及出版的机会。团队将在一起 采用更高的潜水员来理解使用这种人的持续性痛苦的发展 翻译疼痛模型：1）加快预防疗法的测试，2）制定策略以减少 高风险个体手术后的疼痛和OIOID使用，3）在 时期。提供精确的医疗保健并防止慢性术后疼痛和OID使用 最终将改善所有患者的医疗保健。