Behavioral and neurobiological predictors of widespread pain in early adolescence and sex-specific trajectories of pain during puberty

青春期早期广泛疼痛的行为和神经生物学预测因素以及青春期疼痛的性别特异性轨迹

• 批准号: 10442102
• 负责人: Adriene M. Beltz
• 金额: $ 53.18万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-12 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10442102
• 关键词: Adolescence; Adolescent; Adult; Affect; Age; Anterior; Anxiety; Awareness; Back Pain; Behavioral; Biological Factors; Brain; Brain region; CNS processing; Categories; Child; Childhood; Clinical; Cognitive; Data; Data Set; Development; Early Intervention; Early treatment; Etiology; Fatigue; Female; Fibromyalgia; Goals; Hormones; Inflammation; Insula of Reil; Intervention; Knowledge; Lead; Life; Longevity; Longitudinal Studies; Mediating; Memory; Mental Depression; Natural History; Neuraxis; Neurobiology; Neuronal Plasticity; Neurons; Outcome; Pain; Pain-Free; Painless; Pathogenesis; Patient Self-Report; Pattern; Positioning Attribute; Predisposition; Prevention; Prospective cohort study; Puberty; Reporting; Rest; Risk; Risk Factors; Sampling; Sex Differences; Sleep; Sleep disturbances; Somatosensory Cortex; Structure; Symptoms; Testing; Time; Tissues; Visit; Youth; associated symptom; chronic pain; chronic painful condition; chronic widespread pain; cognitive development; cohort; early adolescence; falls; gray matter; high risk; male; midbrain central gray substance; multisensory; negative affect; neuroimaging; pain processing; pain sensitivity; prepuberty; prevent; relating to nervous system; sex

Abstract Chronic pain during childhood and adolescence is a significant personal and societal burden, affecting 20–25% of youth. Unfortunately, treatment is difficult and long-term outcomes are poor, in part due to the limited understanding of how chronic pain manifests across the first two decades of life. Chronic widespread pain is common in adults, and often occurs in absence or not in proportion to tissue damage or inflammation. In adults, widespread pain is associated with altered processing in the central nervous system (CNS), is more common in females, and is accompanied by a cluster of co-occurring centrally-mediated somatic symptoms, including fatigue, sleep disturbances, memory difficulties and depression/anxiety. The alterations in CNS processing typically fall into two broad categories: increased pronociceptive and decreased antinociceptive activity and functional connectivity. While there is strong evidence that adults with conditions characterized by widespread pain, such as fibromyalgia, can trace their pain back to childhood and adolescence, the lack of information about the development of widespread pain in children has made it impossible to tell whether these co-occurring symptoms and CNS changes precede, correlate with, or are consequences of pain. The Adolescent Brain and Cognitive Development (ABCD) study, a large prospective cohort study of childhood development, provides an unparalleled opportunity to explore the early genesis and trajectory of widespread pain in adolescence. Our overarching hypothesis is that CNS factors and clinical outcomes shown to be associated with widespread pain in adults, are also present in children who are at risk for developing widespread pain early in life. Moreover, we hypothesize that there is a sex-related divergence in these factors during pubertal development which leads to an increase in pain sensitivity and vulnerability in females and a decrease in males. To test these hypotheses, we propose three specific aims. Aim 1: Examine clinical and neurobiological differences in children with widespread pain. We will compare symptoms, resting state brain connectivity and gray matter structure in children (ages 11/12) who report widespread pain versus pain-free controls. Aim 2: In a new cohort of pain-free children, determine clinical and neurobiological risk factors for developing widespread pain two years later. We will compare commonly co-occurring non-painful symptoms, brain structure and connectivity from pain-free children (ages 11/12) who develop new widespread pain at ages 13/14, versus children who do not develop pain. Aim 3: Explore clinical and neurobiological sex differences in the trajectories of widespread pain as youth transition through puberty. The proposed study will be the first appropriately powered longitudinal study to examine newly incident widespread pain in children and examine both clinical and neuroimaging predictors. This knowledge could help identify children at high-risk for chronic widespread pain in adulthood and provide a window of opportunity for early interventional strategies.

抽象的 儿童期和青春期的慢性疼痛是一个重大的个人和社会负担，影响 20-25% 的青春。不幸的是，治疗很困难，长期结果也很差，部分原因是有限的 了解慢性疼痛在生命的前二十年如何表现。慢性广泛性疼痛是 常见于成人，并且通常在不存在或与组织损伤或炎症不成比例的情况下发生。在 成年人中，广泛的疼痛与中枢神经系统（CNS）的处理改变有关， 常见于女性，并伴有一系列同时发生的中枢介导的躯体症状， 包括疲劳、睡眠障碍、记忆困难和抑郁/焦虑。中枢神经系统的改变 处理通常分为两大类：伤害感受增加和抗伤害感受减少 活动和功能连接。虽然有强有力的证据表明患有以下特征的成年人 广泛的疼痛，例如纤维肌痛，可以将他们的疼痛追溯到童年和青春期，缺乏 有关儿童普遍疼痛发展的信息使我们无法判断这些疼痛是否会发生。 共同出现的症状和中枢神经系统变化先于疼痛、与疼痛相关或者是疼痛的后果。这 青少年大脑和认知发展（ABCD）研究，一项针对儿童的大型前瞻性队列研究 的发展，提供了一个无与伦比的机会来探索广泛传播的早期起源和轨迹 青春期的痛苦。我们的总体假设是中枢神经系统因素和临床结果被证明是 与成人广泛的疼痛有关，也存在于有发展风险的儿童中 生命早期的广泛疼痛。此外，我们假设这些因素存在与性别相关的差异 在青春期发育期间，这会导致女性疼痛敏感性和脆弱性增加， 男性减少。为了检验这些假设，我们提出了三个具体目标。目标 1：检查临床和 广泛疼痛儿童的神经生物学差异。我们将比较症状、静息状态下的大脑 报告广泛疼痛与无痛的儿童（11/12 岁）的连通性和灰质结构 控制。目标 2：在新的无痛儿童队列中，确定无痛儿童的临床和神经生物学危险因素 两年后出现广泛的疼痛。我们将比较常见的同时发生的非疼痛症状， 无痛儿童（11/12 岁）的大脑结构和连接，这些儿童在 13/14 岁的儿童与没有出现疼痛的儿童相比。目标 3：探索临床和神经生物学性别 青少年在青春期过渡时普遍疼痛的轨迹存在差异。拟议的研究将 是第一个适当动力的纵向研究，以检查新发生的儿童广泛疼痛和 检查临床和神经影像学预测因素。这些知识可以帮助识别高危儿童 成年期慢性广泛疼痛，为早期干预策略提供了机会之窗。