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

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。手术后 疼痛的严重程度和持续时间各不相同，但有相当一部分(20%-30%)的患者经历过手术部位 持续一年或更长时间的疼痛。这种持续的术后疼痛会导致身体和精神上的痛苦， 残疾，以及术后长期接触阿片类药物也使患者面临滥用和成瘾的风险。 尽管对急性向慢性转化过程中涉及的分子事件进行了出色的临床前研究 受伤后疼痛，在将这些发现转化为实际预防术后持续性疼痛方面收效甚微 在人类患者身上已经实现了。我们的研究计划专注于建立一个工作的人体模型 通过对各种手术前、中和后疼痛的系统和纵向研究，了解这一转变。 重要的是，我们已经集中精力识别风险因素，以预测那些实际会发生疾病的人 慢性手术后疼痛，而不是那些不愿意(70%-80%)的人，以使这个问题的研究更有效率。 决定手术后疼痛轨迹的一个重要因素似乎是 在疼痛系统的回路中放大，从而传入的疼痛输入可以增加到 强烈的不适。在我们的心理物理实验室中，我们研究表明过度(时间)的测量方法 疼痛总和(TSP)或延长反应(感觉后疼痛，PAS)放大反应 神经系统对标准化疼痛刺激的反应。放大效应也可以在心理社会层面上发生， 压力、睡眠中断和灾难会增加痛感。这些因素远不止这些 在一些个体中突出，并在术后疼痛严重程度的差异中占相当大的比例。 我们已经调整了这些测试，以便在个体中轻松和非侵入性地测试这种“扩增表型”。 在手术前，使用改良的床边定量感觉测试和有效问卷。 我们建议使用这些措施的术前扩增表型，以帮助靶点 为最需要的人提供已知和新颖的非阿片类药物预防性治疗。这个 研究团队由一名接受过疼痛神经科学正式培训的麻醉师领导，其中包括一名博士 心理学家兼调查员。我们在成功推出博士后研究员方面有着良好的记录 他们自己的独立研究事业。让奥弗斯特里特先生加入我们的团队将使他有必要 培训，指导，接触一个新的研究领域，以及出版的机会。团队将共同努力 有更多不同的方法来理解持续性疼痛的发展 转化型疼痛模型：1)加快疼痛预防疗法的测试，2)制定策略以减少 高危患者术后疼痛和阿片类药物的使用，以及3)在 围手术期。提供精准的医疗护理，防止术后慢性疼痛和阿片类药物的使用 最终将改善所有患者的医疗保健。

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.