PRROPS: Pathways of Risk and Resilience for Overlapping Pain and Sensitization

PRROPS：重叠疼痛和敏感化的风险和弹性途径

• 批准号: 10451514
• 负责人: Emelia J. Benjamin
• 金额: $ 65.6万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-15 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10451514
• 关键词: Abdominal Pain; Address; Adult; Affect; Age; American; Anatomy; Arthralgia; Autonomic Dysfunction; Autonomic nervous system; Back Pain; Body part; Chronic; Cohort Studies; Communities; Data; Degenerative polyarthritis; Development; Diagnosis; Disease; Elderly; Electrocardiogram; Epidemiologist; Evolution; Framingham Heart Study; Functional disorder; Generations; Genetic; Genotype; Grant; Health; Health Personnel; Heritability; High Prevalence; Impairment; Incidence; International; Knowledge; Light; Location; Measures; Migraine; Nature; Nervous System Physiology; Nervous system structure; Nociception; Pain; Pain management; Participant; Pathway interactions; Patient Self-Report; Patients; Physical activity; Physicians; Preventive; Psychologist; Risk; Risk Factors; Sensory; Severities; Signal Transduction; Sleep; Smell Perception; Social support; Specialist; Spirituality; Stimulus; Testing; Therapeutic; Time; Visit; Work; aged; base; chronic pain; chronic painful condition; cohort; cost; cost estimate; disability; experience; follow up assessment; heart rate variability; high risk; innovation; insight; interdisciplinary collaboration; middle age; multidisciplinary; multisensory; neurophysiology; novel; novel strategies; offspring; opioid epidemic; optimism; pain processing; resilience; rheumatologist; risk sharing; sleep quality; sound

Chronic pain affects >100 million American adults with estimated costs of up to $1 trillion annually. Older adults are at increased risk of having multiple painful conditions and are living longer with the negative impacts of chronic pain. Chronic pain, regardless of anatomy or diagnosis involved (e.g., back pain, migraine), is the leading cause of disability worldwide. Limited insights into whether common mechanisms underlie all pain conditions, regardless of diagnosis, has contributed to inadequate pain management options, and in turn, to the opioid epidemic. Health care providers who treat one pain condition (e.g., joint pain) typically do not manage symptoms in other parts of the body (e.g., abdominal pain), and patients are often referred from one specialist to another. Studying commonalities of various chronic overlapping pain conditions (COPC) in community-based cohorts unselected for pain conditions can provide novel insights into causes of chronic pain as a disease itself, and into shared risk factors that may be promising targets to help ameliorate chronic pain regardless of diagnosis. Alterations in nociceptive signaling such as pain sensitization assessed by quantitative sensory testing (QST) may commonly underlie chronic pain, but why such alterations occur is not known, and whether such nociceptive signaling changes are heritable is also not known. Beyond nociception, there may be broader nervous system dysfunction underlying chronic pain. Generalized heightened sensitivity to external stimuli (e.g., light, sound) and impaired autonomic nervous system functioning, reflected by diminished heart rate variability (HRV), are associated with chronic pain, but it is unclear if they contribute to COPC, QST-assessed abnormalities, or development of chronic pain. Treatments targeting these potential risk factors could represent new avenues for pain management. Another untapped potential is in understanding whether positive factors such as resilience, sleep quality, and physical activity can be harnessed to alter risk of COPC or QST abnormalities. We propose evaluating COPC in the upcoming study visit of a community-based middle age and older adult cohort unselected for any pain complaints, the 3rd Generation of the Framingham Heart Study (FHS) (N~3374, mean age 60). We aim to understand the relation of multisensory sensitivity, autonomic function, resilience, sleep, and physical activity to COPC, QST-assessed pain processing and evolution of chronic pain over time; and to study heritability of QST abnormalities. Understanding the relation of these novel factors to COPC and QST would spur development of novel pain management approaches for all types of pain regardless of diagnosis involved. We will collect data regarding common chronic pain complaints, QST (to assess pain sensitization), and proposed risk factors, and conduct two follow-up assessments to obtain longitudinal data. We will leverage the ongoing FHS Offspring (2nd Generation) Exam in which we are collecting the same QST measures to assess heritability of pain processing abnormalities. Our work will address several knowledge gaps, and insights gained may facilitate new approaches to relieving chronic pain and its consequences, regardless of underlying diagnosis.

慢性疼痛影响超过1亿美国成年人，估计每年的费用高达1万亿美元。老年人 患有多种疼痛疾病的风险增加，并且在以下负面影响下寿命更长 慢性疼痛慢性疼痛，无论涉及的解剖结构或诊断（例如，背痛，偏头痛），是 全球残疾的主要原因。对所有疼痛的共同机制是否存在的认识有限 条件，无论诊断如何，都导致疼痛管理选择不足，反过来， 阿片类药物流行病治疗一种疼痛状况的卫生保健提供者（例如，关节疼痛）通常不能管理 身体其他部位的症状（例如，腹痛），患者通常由一位专家转诊 到另研究社区中各种慢性重叠疼痛状况（COPC）的共性 疼痛状况的队列研究可以提供对慢性疼痛作为疾病本身的原因的新见解， 以及共同的风险因素，这些风险因素可能是有希望的目标，以帮助改善慢性疼痛，无论诊断如何。 通过定量感觉测试（QST）评估的伤害性信号传导（如疼痛致敏）的改变 可能通常是慢性疼痛的基础，但为什么会发生这种变化尚不清楚，以及这种伤害性变化是否 信号变化是可遗传的也是未知的。除了伤害感受，可能还有更广泛的神经系统 慢性疼痛的潜在功能障碍。对外部刺激的普遍敏感性增强（例如，光、声）和 自主神经系统功能受损，表现为心率变异性（HRV）降低， 与慢性疼痛相关，但尚不清楚它们是否有助于COPC，QST评估的异常，或 慢性疼痛的发展。针对这些潜在风险因素的治疗可能代表了新的途径， 疼痛管理另一个尚未开发的潜力是了解是否有积极因素，如复原力， 睡眠质量和身体活动可以用来改变COPC或QST异常的风险。我们提出 在即将到来的社区中年和老年人队列研究中评估COPC 对于任何疼痛投诉，第三代心脏瓣膜研究（FHS）（N~3374，平均年龄60岁）。 我们的目的是了解多感觉敏感性，自主神经功能，弹性，睡眠和身体的关系， 活动COPC，QST评估的疼痛处理和慢性疼痛随时间的演变;并研究遗传性 QST异常了解这些新因素与COPC和QST的关系将促进 开发新的疼痛管理方法，用于所有类型的疼痛，无论涉及何种诊断。我们 将收集关于常见慢性疼痛投诉、QST（评估疼痛致敏性）和拟定的 风险因素，并进行两次随访评估，以获得纵向数据。我们将利用正在进行的 FHS后代（第二代）考试，我们正在收集相同的QST措施，以评估遗传性 疼痛处理异常我们的工作将解决几个知识差距，获得的见解可能 促进新的方法来缓解慢性疼痛及其后果，无论潜在的诊断。