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，每年造成的损失估计高达 1 万亿美元。老年人 患有多种痛苦疾病的风险增加，并且由于以下疾病的负面影响而寿命更长 慢性疼痛。慢性疼痛，无论涉及何种解剖或诊断（例如背痛、偏头痛），都是 全球残疾的主要原因。对所有疼痛是否存在共同机制的认识有限 无论诊断如何，病情都会导致疼痛管理选择不足，进而导致 鸦片类药物泛滥。治疗一种疼痛（例如关节痛）的医疗保健提供者通常无法治疗 身体其他部位的症状（例如腹痛），患者通常由一位专科医生转诊 到另一个。研究社区中各种慢性重叠疼痛 (COPC) 的共性 未经选择的疼痛状况队列可以为慢性疼痛作为一种疾病本身的原因提供新的见解， 并研究共同的风险因素，无论诊断如何，这些因素可能是帮助改善慢性疼痛的有希望的目标。 伤害感受信号的改变，例如通过定量感觉测试（QST）评估的疼痛敏感性 通常可能是慢性疼痛的基础，但为什么会发生这种改变尚不清楚，也不知道这种伤害是否会导致疼痛。 信号变化是否可遗传尚不清楚。除了伤害感受之外，可能还有更广泛的神经系统 慢性疼痛背后的功能障碍。对外部刺激（例如光、声音）的普遍敏感性增强 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会导致 COPC、QST 评估异常或 慢性疼痛的发展。针对这些潜在风险因素的治疗可能代表新的途径 疼痛管理。另一个尚未开发的潜力是了解诸如韧性、 睡眠质量和身体活动可以用来改变 COPC 或 QST 异常的风险。我们建议 在即将进行的基于社区的中年和老年人队列的研究访问中评估 COPC（未选择） 对于任何疼痛投诉，请参阅第三代弗雷明汉心脏研究 (FHS)（N~3374，平均年龄 60 岁）。 我们的目标是了解多感官敏感性、自主功能、弹性、睡眠和身体的关系 COPC 活动、QST 评估的疼痛处理以及慢性疼痛随时间的演变；并研究遗传力 QST 异常。了解这些新因素与 COPC 和 QST 的关系将有助于 开发针对所有类型疼痛的新型疼痛管理方法，无论涉及何种诊断。我们 将收集有关常见慢性疼痛投诉、QST（评估疼痛敏感性）的数据，并提出建议 风险因素，并进行两次后续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，我们在其中收集相同的 QST 指标来评估遗传力 疼痛处理异常。我们的工作将解决一些知识差距，所获得的见解可能会 促进缓解慢性疼痛及其后果的新方法，无论潜在的诊断如何。