Fear learning in adolescents with chronic pain: Neural and behavioral mechanisms

患有慢性疼痛的青少年的恐惧学习：神经和行为机制

• 批准号: 9197686
• 负责人: LAURA E SIMONS
• 金额: $ 40.42万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-21 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9197686
• 关键词: Adolescence; Adolescent; Adult; Affect; Aftercare; Amygdaloid structure; Anterior; Behavior; Behavioral; Behavioral Mechanisms; Brain; Child; Childhood; Chronic; Coupled; Coupling; Data; Detection; Development; Distress; Extinction (Psychology); Fright; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Health; Hour; Human; Impairment; Individual; Insula of Reil; Lead; Learning; Measures; Methods; Modification; Neurobiology; Neurons; Outcome; Pain; Pain management; Parents; Patients; Pattern; Persistent pain; Predisposition; Prefrontal Cortex; Prevalence; Process; Property; Protocols documentation; Psychological reinforcement; Public Health; Research; Research Proposals; Risk; Risk Factors; Rodent; Safety; Schools; Stimulus; Stress; System; Techniques; Time; Work; Youth; avoidance behavior; base; chronic pain; cognitive control; conditioning; depressive symptoms; disability; experience; fear memory; health care service utilization; improved; learning extinction; neural circuit; neurobiological mechanism; neuroimaging; neuromechanism; novel; parental influence; prevent; protective behavior; psychologic; public health relevance; resilience; response; therapy resistant

PROJECT SUMMARY Chronic pain in childhood is a significant public health concern with median prevalence rates of 11 to 38%, with 3 to 5% of children suffering from significant pain-related disability (~3.5 million children in the US). Notwithstanding the physical and psychological consequences on overall health, chronic pain in childhood results in high levels of healthcare utilization and can predispose the development of chronic pain in adulthood. Fear is a particularly salient influence on pain outcomes and is the focus of the current research proposal. A significant proportion of youth with chronic pain endorse elevated pain-related fear. Pain-related fear is associated with high levels of disability, depressive symptoms, and school impairment. Beyond the individual, contextual influences substantially impact fear learning. Parents are profoundly affected when their child experiences pain and their (mal)adaptive response impacts outcomes. Thus, defining adolescent fear learning in chronic pain must incorporate parent distress and behavior. In the context of treatment, decreasing pain- related fear is associated with improved physical and psychological functioning, while high initial pain-related fear is a risk factor for less treatment responsiveness. Although it is recognized that high levels of pain-related fear can be detrimental, the neurobiological mechanisms for acquisition and extinction of fear have yet to be defined in pain patients. This is particularly germane during adolescence where neuronal properties are primed for modification by experience and the peak onset of chronic pain in childhood occurs. Moreover, extinction, the primary means of eradicating fear, is not consistently effective as fear may return when in a new context or under stress. Thus, more robust techniques are needed to diminish fear in a context-independent fashion. One method to prevent the return of fear is disruption of fear memory reconsolidation, where extinction occurs in a time window during which the fear memory is labile. This method, established in rodents and humans, has yet to be demonstrated in pediatric pain patients. This proposal investigates the mechanisms underlying fear learning, fear extinction, and disruption of fear reconsolidation in adolescents with chronic pain and healthy controls using behavioral and neuroimaging measures with the long-term goal of improving exposure-based treatments for adolescents with chronic pain. Aim 1 examines acquisition and extinction of fear learning behaviorally and neurobiologically in adolescents with chronic pain and low or high pain-related fear and healthy controls with consideration of the influence of parent fear and avoidance behavior. Aim 2 examines enhancement of fear extinction with disruption of fear memory reconsolidation. Currently, the treatment of chronic pain is suboptimal. Significant breakthroughs require a mechanistic understanding of key processes underlying pain-related dysfunction. Defining behavioral and neurobiological mechanisms of fear learning and extinction will lead to advancements in our understanding and treatment of persistent pain in adolescents.

项目概要 儿童慢性疼痛是一个重要的公共卫生问题，中位患病率为 11% 至 38%，其中 3% 到 5% 的儿童患有与疼痛相关的严重残疾（美国约有 350 万儿童）。 尽管儿童期的慢性疼痛会对身体和心理产生影响，但 导致医疗保健利用率高，并可能导致成年后出现慢性疼痛。 恐惧对疼痛结果的影响尤为显着，也是当前研究提案的重点。一个 相当一部分患有慢性疼痛的青少年认可与疼痛相关的恐惧。与疼痛有关的恐惧是 与高度残疾、抑郁症状和学业障碍有关。超越个人， 情境影响极大地影响恐惧学习。当孩子的时候，父母会受到深刻的影响 经历疼痛及其（不良）适应性反应会影响结果。因此，定义青少年恐惧学习 慢性疼痛必须结合父母的痛苦和行为。在治疗过程中，减少疼痛 相关的恐惧与身体和心理功能的改善有关，而高初始疼痛相关 恐惧是治疗反应较差的一个危险因素。尽管人们认识到与疼痛相关的高水平 恐惧可能是有害的，但恐惧获得和消除的神经生物学机制尚未阐明 定义为疼痛患者。这在青春期尤其重要，因为青春期的神经元特性 准备好根据经验进行修改，并且在儿童时期出现慢性疼痛的高峰期。而且， 灭绝是消除恐惧的主要手段，但并不总是有效，因为恐惧可能会在新的环境中卷土重来。 环境或压力下。因此，需要更强大的技术来减少与情境无关的恐惧。 时尚。防止恐惧卷土重来的一种方法是破坏恐惧记忆的重新巩固，其中 消退发生在恐惧记忆不稳定的时间窗口内。这种方法是在啮齿类动物身上建立的 和人类一样，尚未在儿科疼痛患者中得到证实。该提案研究了机制 患有慢性疼痛的青少年潜在的恐惧学习、恐惧消退和恐惧再巩固的破坏 使用行为和神经影像学措施进行健康控制，长期目标是改善 针对患有慢性疼痛的青少年进行基于暴露的治疗。目标 1 考察 患有慢性疼痛以及低度或高度疼痛相关的青少年在行为和神经生物学上学习恐惧 恐惧和健康控制，考虑父母恐惧和回避行为的影响。目标2 检查恐惧消退的增强与恐惧记忆重新巩固的破坏。目前， 慢性疼痛的治疗效果欠佳。重大突破需要对关键因素有机械性的理解 处理潜在的疼痛相关功能障碍。定义恐惧的行为和神经生物学机制 学习和消退将促进我们对持续性疼痛的理解和治疗的进步 青少年。