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.

项目摘要 每年有超过2.3亿人接受手术。术后疼痛的经历在以下方面各不相同： 个体，但相当大比例（20-30%）的患者经历手术部位疼痛持续至少一年 手术后。这种持续性术后疼痛（PPSP）会导致身体和精神上的痛苦， 残疾和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 基础研究中的优秀研究表明，急性向急性转化的潜在机制 慢性疼痛，很少成功地将这些发现转化为实际预防术后持续疼痛， 人类患者已经实现。我的研究项目已经开发出了一个人体模型 过渡，通过系统和纵向研究疼痛之前，期间和之后的各种手术。我们有 确定了几个患者水平的风险因素，预测谁是发展PPSP的高风险， 有效的研究这个问题，以及洞察相关机制，在人类。 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。虽然疼痛放大可能在短期内具有保护作用，但它 如果过度或持续，则功能失调。在我们的心理物理学实验室里，我们研究表明过度 在某些个体中，神经系统对标准化疼痛测试的反应是放大反应。我们 还测量心理社会因素，如压力，睡眠中断和灾难化（一种心理过程， 沉思、放大和担忧会增加突出性和重要性），这也会放大痛苦。 信号了重要的是，疼痛放大在某些个体中更为突出，并占相当大的比例。 手术引起的疼痛变化量（远远超过手术范围）。我们有 开发了一个系统，可以轻松地和非侵入性地测试这种“扩增表型”的个人之前， 手术，使用改良的床边定量感觉测试，和简短的，有效的心理社会问卷。 我的研究项目优化了我们病人术前放大的测量 表型，以帮助将已知和新型非阿片类药物预防性治疗靶向这些高危个体。 我们在未来5年的R35奖项的目标是：（1）有效地针对预防持续性疼痛 和阿片类药物的使用在手术后的高风险个人，（2）了解和目标的潜在机制 有助于PPSP的发展，包括了解疼痛放大与疼痛的关系。 炎症反应的手术，（3）更广泛地应用预防策略，了解他们的 不同患者样本之间的疗效差异。作为一名受过疼痛训练的麻醉师 神经科学，心理物理和心理社会评估，以及在进行 翻译研究，我很好地定位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.

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

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