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

慢性疼痛影响着1亿美国成年人，估计每年造成高达1万亿美元的损失。老年人 有多种痛苦状况的风险增加，并因以下负面影响而活得更长 慢性疼痛。慢性疼痛，无论涉及的解剖或诊断(例如，背痛、偏头痛)，是 全球导致残疾的主要原因。对于共同机制是否构成所有痛苦的基础的见解有限 病情，无论诊断如何，都导致疼痛管理选择不足，进而导致 阿片类药物泛滥。治疗一种疼痛情况(例如关节疼痛)的医疗保健提供者通常不会 身体其他部位的症状(例如，腹痛)，患者通常由一名专家转介 给另一个人。社区不同慢性重叠疼痛状况(COPC)的共性研究 没有选择疼痛状况的队列可以提供对慢性疼痛作为一种疾病本身的原因的新见解， 并将其转化为共同的风险因素，这些因素可能是帮助缓解慢性疼痛的有希望的目标，无论诊断如何。 定量感觉测试(QST)评估痛敏化等伤害性信号的变化 可能通常是慢性疼痛的基础，但为什么会发生这种变化，以及这种伤害性感受是否存在，目前尚不清楚 信号变化是可遗传的也是未知的。除了伤害性感受，可能还有更广泛的神经系统 慢性疼痛的基础是功能障碍。对外部刺激(例如，光、声音)的普遍提高的敏感性 自主神经系统功能受损，反映为心率变异性(HRV)降低 与慢性疼痛有关，但尚不清楚它们是否导致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是治疗 疼痛管理。另一个尚未开发的潜力是理解诸如韧性等积极因素， 可以利用睡眠质量和体力活动来改变COPC或QST异常的风险。我们建议 在即将到来的以社区为基础的中老年队列研究访问中评估COPC 对于任何疼痛主诉，弗雷明翰心脏研究(FHS)的第三代(N~3374，平均年龄60岁)。 我们的目标是了解多感官敏感性、自主神经功能、弹性、睡眠和身体之间的关系。 COPC，QST-评估疼痛处理和慢性疼痛随时间的演变的活动；并研究遗传度 QST异常。了解这些新因素与COPC和QST的关系将会刺激 为所有类型的疼痛开发新的疼痛管理方法，而不考虑所涉及的诊断。我们 将收集有关常见慢性疼痛主诉、QST(用于评估疼痛敏感化)的数据，并建议 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，我们收集相同的QST测量来评估遗传度 疼痛处理的异常。我们的工作将解决几个知识差距，所获得的见解可能 促进缓解慢性疼痛及其后果的新方法，而不考虑潜在的诊断。

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.