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: 10609081
• 负责人: Adriene M. Beltz
• 金额: $ 49.23万
• 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/10609081
• 关键词: Adolescence; Adolescent; Adult; Affect; Age; Anterior; Anxiety; Awareness; Back Pain; Behavioral; Biological Factors; Brain; Brain region; CNS processing; Categories; Central Nervous System; Child; Childhood; Clinical; Cognitive; Data; Data Set; Development; Early Intervention; Early treatment; Etiology; Fatigue; Female; Fibromyalgia; Goals; Hormones; Inflammation; Insula of Reil; Intervention; Knowledge; Life; Longevity; Longitudinal Studies; Mediating; Memory; Mental Depression; Natural History; 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; Site; Sleep; Sleep disturbances; Somatosensory Cortex; Structure; Symptoms; Testing; Time; Tissues; Visit; Youth; antinociception; 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; neural; neuroimaging; pain processing; pain sensitivity; prepuberty; prevent; 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 童年时期和青少年时期的慢性疼痛是一个重要的个人和社会伯恩，影响20-25％ 青年。不幸的是，治疗很困难，长期结局很差，部分原因是 了解慢性疼痛如何在生命的前二十年中表现出来。慢性宽度疼痛是 在成年人中常见，通常是在没有组织损伤或炎症成比例的情况下发生的。在 成人，宽度疼痛与中枢神经系统（CNS）中的处理改变有关，更多的是 在女性中常见，并伴随着一群共发生的集中介导的躯体症状， 包括疲劳，睡眠障碍，记忆力难度和抑郁/焦虑。中枢神经系统的变化 处理通常分为两个广泛的类别：增加引起感受和抗伤害感受 活动和功能连接。虽然有强有力的证据表明，其状况为特征的成年人 宽度疼痛，例如纤维肌痛，可以追溯到童年和青少年，缺乏疼痛 有关儿童宽度疼痛发展的信息使得无法判断 同时出现的症状和中枢神经系统的变化之前，与疼痛的后果相关或是疼痛的后果。 青少年大脑和认知发展（ABCD）研究，一项针对童年的前瞻性队列研究 开发，提供了一个无与伦比的机会来探索宽度的早期起源和轨迹 青少年疼痛。我们的总体假设是CNS因素和临床结果显示为 与成人的宽度疼痛相关的儿童也存在于成人 生命早期的宽度疼痛。此外，我们假设这些因素存在与性别有关的差异 在青春期发育期间，导致女性疼痛敏感性和脆弱性的增加 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 宽度疼痛的儿童的神经生物学差异。我们将比较症状，静止状态大脑 儿童的连通性和灰质结构（11/12岁）报告宽度疼痛与无疼痛 控件。目标2：在新的无痛儿童队列中，确定的临床和神经生物学风险因素 两年后，出现宽度疼痛。我们将比较通常共同出现的非抚摸症状， 大脑结构和无痛儿童的连通性（11/12岁），他们在 目标3：探索临床和神经生物学性别 随着青春期过渡，宽度疼痛的轨迹差异。拟议的研究将 成为第一个适当动力的纵向研究，以检查儿童和 检查临床和神经成像预测因子。这些知识可以帮助识别高风险的儿童 成年后的慢性宽度疼痛，为早期介入策略提供了机会之窗。