Personalizing Perioperative Preventive Analgesia: Translational Studies Investigating the Biopsychosocial Underpinnings of Enhanced Pain Propensity

个性化围手术期预防性镇痛：调查疼痛倾向增强的生物心理社会基础的转化研究

• 批准号: 10623386
• 负责人: KRISTIN SCHREIBER
• 金额: $ 51.91万
• 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 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10623386
• 关键词: Absence of pain sensation; Anguish; Anxiety; Award; Basic Science; Clinical Research; Development; Doctor of Philosophy; Exposure to; Goals; Human; Individual; Inflammatory; Inflammatory Response; Intervention; Longitudinal Studies; Measurable; Measurement; Measures; Mediator; Mental Processes; Nervous System; Neurosciences; Operative Surgical Procedures; Opioid Analgesics; Pain; Patients; Perioperative; Persistent pain; Persons; Phenotype; Physical Sufferings; Postoperative Pain; Postoperative Period; Predictive Factor; Prevention; Prevention strategy; Preventive; Preventive treatment; Psychophysics; Psychosocial Assessment and Care; Psychosocial Factor; Questionnaires; Research; Risk; Risk Factors; Sampling; Sensory; Site; Sleep disturbances; Standardization; Stress; System; Testing; Training; Translating; Variant; addiction; biopsychosocial; clinically significant; design; disability; experience; high risk; high risk population; human model; insight; non-opioid analgesic; novel; opioid use; pain chronification; pain signal; prevent; programs; psychosocial; response; rumination; success; translational study

PROJECT SUMMARY Over 230 million people undergo surgery annually. The experience of postsurgical pain varies among individuals, but a significant proportion (20-30%) of patients experience surgical site pain lasting at least a year postoperatively. Such Persistent Post-Surgical Pain (PPSP) causes physical and mental suffering and disability and lengthens exposure to opioid analgesics, potentially placing patients at risk of addiction. Despite excellent research in basic research indicating potential mechanisms involved in the transition of acute to chronic pain, little success at translating these findings to actual prevention of persistent postoperative pain in human patients has been realized. My research program has developed a working human model of this transition, by systematic and longitudinal studying pain before, during and after a variety of surgeries. We have identified several patient-level risk factors that predict who is high-risk for developing PPSP, allowing more efficient study of this problem, as well as insight into relevant mechanisms, in humans. A crucially important factor in determining the trajectory of PPSP appears to be the tendency for the pain signal to be amplified. While pain amplification may be protective in the short term, it becomes dysfunctional if excessive or persistent. In our psychophysics lab, we study measures that indicate excessive amplification response of the nervous system in some individuals in response to standardized pain testing. We also measure psychosocial factors such as stress, sleep disruption, and catastrophizing (a mental process by which rumination, magnification, and worry increase salience and importance), which can also amplify the pain signal. Importantly, pain amplification is more prominent in some individuals, and accounts for a sizeable amount of the variation in pain resulting from surgery (and far more than the surgical extent). We have developed a system to easily and non-invasively test this “amplification phenotype” in individuals BEFORE surgery, using modified bedside quantitative sensory tests, and brief, validated psychosocial questionnaires. My research program has optimized measurement of our patients’ preoperative amplification phenotype, to help target both known and novel non-opioid preventive treatments to these high-risk individuals. Our goals for the next 5 years of this R35 award are: (1) to efficiently target the prevention of persistent pain and opioid use after surgery in high-risk individuals, (2) to understand and target the underlying mechanisms contributing to the development of PPSP, including understanding how pain amplification relates to the inflammatory response to surgery, (3) to more widely apply preventive strategies, understanding their differential efficacy among diverse samples of patients. As an Anesthesiologist with formal training in pain neuroscience, psychophysical and psychosocial assessments, and practical experience in conducting translational studies, I am well-situated to conduct such well-designed mechanistic studies.

项目概要 每年有超过 2.3 亿人接受手术。术后疼痛的经历因人而异 个人，但很大一部分 (20-30%) 的患者经历手术部位疼痛至少持续一年 术后。这种持续性术后疼痛（PPSP）会导致身体和精神上的痛苦， 残疾并延长阿片类镇痛药的暴露时间，可能使患者面临成瘾的风险。尽管 基础研究中的出色研究表明了急性向急性发作转变的潜在机制 慢性疼痛，在将这些发现转化为实际预防持续性术后疼痛方面收效甚微 人类患者已经实现。我的研究项目开发了一个有效的人体模型 通过系统和纵向研究各种手术之前、期间和之后的疼痛来实现过渡。我们有 确定了几个患者层面的风险因素，可以预测谁是发生 PPSP 的高风险人群，从而使更多人能够 对人类这个问题的有效研究以及对相关机制的深入了解。 决定 PPSP 轨迹的一个至关重要的因素似乎是 疼痛信号被放大。虽然疼痛放大在短期内可能具有保护作用，但它变得 如果过度或持续，就会出现功能障碍。在我们的心理物理学实验室，我们研究表明过度 一些个体的神经系统对标准化疼痛测试的放大反应。我们 还可以测量心理社会因素，例如压力、睡眠中断和灾难化（一种心理过程） 沉思、放大和担忧会增加显着性和重要性），这也会放大痛苦 信号。重要的是，疼痛放大在某些个体中更为突出，并且占相当大的比例。 手术引起的疼痛变化量（并且远远超过手术范围）。我们有 开发了一种系统，可以轻松、无创地测试个体的这种“扩增表型” 手术，使用改良的床边定量感官测试以及简短的、经过验证的社会心理问卷。 我的研究计划优化了患者术前扩增的测量 表型，以帮助针对这些高危人群进行已知和新型非阿片类药物预防治疗。 我们的 R35 奖项未来 5 年的目标是：(1) 有效地预防持续性疼痛 以及高危人群手术后阿片类药物的使用，(2) 了解并针对潜在机制 为 PPSP 的发展做出贡献，包括了解疼痛放大与 对手术的炎症反应，（3）更广泛地应用预防策略，了解其 不同患者样本之间的疗效存在差异。作为接受过正规疼痛培训的麻醉师 神经科学、心理物理学和心理社会评估以及进行实践的经验 转化研究，我完全有能力进行这种精心设计的机制研究。

项目成果

Increased pain catastrophizing longitudinally predicts worsened pain severity and interference in patients with chronic pain and cancer: A collaborative health outcomes information registry study (CHOIR).

• DOI: 10.1002/pon.6020
• 发表时间: 2022-10
• 期刊: PSYCHO-ONCOLOGY
• 影响因子: 3.6
• 作者: Wilson, Jenna M.;Schreiber, Kristin L.;Mackey, Sean;Flowers, K. Mikayla;Darnall, Beth D.;Edwards, Robert R.;Azizoddin, Desiree R.
• 通讯作者: Azizoddin, Desiree R.

Social Support and Psychological Distress among Chronic Pain Patients: The Mediating Role of Mindfulness.

慢性疼痛患者的社会支持和心理困扰：正念的中介作用。

• DOI: 10.1016/j.paid.2022.111551
• 发表时间: 2022
• 期刊: Personality and individual differences
• 影响因子: 4.3
• 作者: Wilson,JennaM;Colebaugh,CarinA;Flowers,KMikayla;Meints,SamanthaM;Edwards,RobertR;Schreiber,KristinL
• 通讯作者: Schreiber,KristinL

Applying the Rapid OPPERA Algorithm to Predict Persistent Pain Outcomes Among a Cohort of Women Undergoing Breast Cancer Surgery.

• DOI: 10.1016/j.jpain.2022.07.012
• 发表时间: 2022-12
• 期刊: JOURNAL OF PAIN
• 影响因子: 4
• 作者: Wilson, Jenna M.;Colebaugh, Carin A.;Flowers, K. Mikayla;Overstreet, Demario;Edwards, Robert R.;Maixner, William;Smith, Shad B.;Schreiber, Kristin L.
• 通讯作者: Schreiber, Kristin L.

A prospective, randomized comparison of ultrasonographic visualization of proximal intercostal block vs paravertebral block.

近端肋间阻滞与椎旁阻滞超声可视化的前瞻性、随机比较。

• DOI: 10.1186/s12871-020-0929-x
• 发表时间: 2020
• 期刊: BMC anesthesiology
• 影响因子: 2.2
• 作者: Vlassakov,Kamen;Vafai,Avery;Ende,David;Patton,MeganE;Kapoor,Sonia;Chowdhury,Atif;Macias,Alvaro;Zeballos,Jose;Janfaza,DavidR;Pentakota,Sujatha;Schreiber,KristinL
• 通讯作者: Schreiber,KristinL

Personalization over Protocolization.

• DOI: 10.1097/aln.0000000000003695
• 发表时间: 2021-03-01
• 期刊: Anesthesiology
• 影响因子: 8.8
• 作者: Schreiber KL;Muehlschlegel JD
• 通讯作者: Muehlschlegel JD