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。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。我们的研究计划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重要因素似乎是 疼痛系统的回路中的放大，由此传入的疼痛输入可以增加到 强烈的不适感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， 其中压力、睡眠中断和灾难化增加了疼痛感。这些因素要多得多 在某些个体中是突出的，并且解释了术后疼痛严重程度的相当大的变化。 我们已经调整了这些测试，以方便和非侵入性的测试这种“扩增表型”的个人 在他们接受手术之前，使用改良的床边定量感觉测试和有效的问卷调查。 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。的 一个研究小组由一名接受过疼痛神经科学正规培训的麻醉师领导， 心理学家合作调查员。我们有一个成功地推出博士后研究员进入强大的跟踪记录 自己的独立研究生涯。奥弗斯特里特先生加入我们的团队 培训、指导、接触新的研究领域以及出版机会。整个团队将 有一个更多样化的方法来理解持续性疼痛的发展，使用这个人类 翻译疼痛模型：1）加速疼痛预防疗法的测试，2）制定减少疼痛的策略， 疼痛和阿片类药物的使用，以及3）在高风险人群中推广个性化药物， 围手术期提供精准医疗护理，预防慢性术后疼痛和阿片类药物使用 将最终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.