Genetic and Environmental Origins of the Development of Pain in Children

项目摘要 儿童慢性疼痛是一种常见但未充分研究的健康问题， 从童年到青春期，尤其是女孩。此外，在过去， 20年，原因不明。尽管流行率高，影响持久，但我们对其知之甚少。 病因学和发育进展。文献记录了早期暴露于 逆境和慢性疼痛的成年人，但很少有人知道的早期发展的时间过程，关键 机制和社会复原力，可以减轻青年的风险。需要解决的关键问题 在预防和干预努力能够产生最大影响之前。为此，拟议的竞争性 延续项目的重点是四个目标：确定遗传和环境对疼痛生长的影响 跨越童年和青春期（目标1）;检查压力暴露在发展中的作用， 儿童的慢性疼痛（目标2）;并评估两个潜在的机制，联系压力和疼痛，问题与 情绪调节（目标3）和表观遗传学（目标4）。在重新校准模型下，我们还探索了社会 青春期的复原力作为这些风险过程的缓冲。为了实现我们的目标，我们建议进行 一项基于出生记录的强化纵向随访评估（14、15和16岁） 社区样本350对双胞胎谁是不同的种族和社会经济地位。压力， 情绪调节，以及在儿童早期和中期反复出现的疼痛， 表征了青春期的评估将采用多方法，包括临床和 疼痛频率、强度、持续时间的日记评估; 情绪调节、压力和社会适应力;以及对表观遗传学的客观评估。我们的基因 了解青少年疼痛的病因和机制的知情发展方法是至关重要的， 确定良性慢性疼痛何时具有临床意义，并确定干预工作的关键目标 预防青年人慢性疼痛的发展并促进其康复。

Project Summary Pediatric chronic pain is a common but understudied health problem, with prevalence increasing from childhood to adolescence, particularly among girls. Moreover, prevalence rates have increased over the past 20 years for unknown reasons. Despite the high prevalence and enduring impact, we know little about its etiology and developmental progression. The literature documents associations between exposure to early adversity and chronic pain among adults, but little is known about the early developmental time course, key mechanisms, and social resilience that can mitigate risk in youth. Critical questions need to be addressed before efforts at prevention and intervention can have maximum impact. To that end, the proposed competing continuation project focuses on four aims: identify the genetic and environmental influences on growth in pain across childhood and adolescence (Aim1); examine the role of stress exposure in the development of children's chronic pain (Aim 2); and evaluate two potential mechanisms linking stress and pain, problems with emotion regulation (Aim 3), and epigenetics (Aim 4). Under a recalibration model, we also explore social resilience in adolescence as a buffer of these risk processes. To accomplish our aims, we propose to conduct intensive longitudinal follow-up assessments (at 14, 15, and 16 years of age) of a birth-records-based community sample of 350 pairs of twins who are diverse in ethnicity and socioeconomic status. Stress, emotion regulation, and recurring pain during early and middle childhood have already been well characterized. Assessments during adolescence will take a multi-method approach that includes clinical and diary assessments of pain frequency, intensity, duration; objective, diary, and questionnaire assessments of emotion regulation, stress, and social resilience; and objective assessments of epigenetics. Our genetically informed developmental approach to understanding the etiology and mechanisms of pain in youth is critical to determining when benign chronic pain is clinically significant and identifying key targets for intervention efforts to prevent the development of and promote recovery from chronic pain among youth.