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: 9757799
• 负责人: LAURA E SIMONS
• 金额: $ 46.97万
• 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 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9757799
• 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; Suggestion; 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; pain catastrophizing; pain outcome; pain patient; 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.

项目摘要 童年时期的慢性疼痛是一个重大的公共卫生问题，中位患病率为11至38％，其中 患有严重疼痛有关的残疾儿童中有3％至5％（美国约350万儿童）。 尽管对整体健康有身体和心理后果，但童年的慢性疼痛 导致高水平的医疗保健利用，并且可能会倾向于成年后慢性疼痛的发展。 恐惧是对疼痛结果的特别显着影响，并且是当前研究建议的重点。一个 慢性疼痛的年轻人很大一部分支持与疼痛有关的恐惧。与疼痛有关的恐惧是 与高水平的残疾，抑郁症状和学校障碍有关。超越个人， 上下文影响会影响恐惧学习。父母在孩子时受到深远的影响 经历疼痛及其（MAL）自适应反应会影响结果。因此，定义青少年恐惧学习 在慢性疼痛中，必须纳入父母的困扰和行为。在治疗的背景下，减轻疼痛 - 相关的恐惧与身体和心理功能的改善有关，而与初始疼痛有关 恐惧是减少治疗反应能力的危险因素。尽管人们认识到高水平的疼痛相关 恐惧可能是有害的，恐惧的获取和灭绝的神经生物学机制尚未 在疼痛患者中定义。这在神经元特性的青春期尤为明显 通过经验进行修改和儿童期慢性疼痛的峰值发作。而且， 灭绝是消除恐惧的主要手段，并不是一致的有效，因为恐惧可能会在新的 背景或压力下。因此，需要更强大的技术来减少与环境无关的恐惧 时尚。防止恐惧返回的一种方法是破坏恐惧记忆的重新整理， 灭绝发生在恐惧记忆不稳定的时间窗口中。这种方法，建立在啮齿动物中 和人类在小儿疼痛患者中尚未证明。该提案调查了机制 恐惧学习，恐惧灭绝和恐惧重新整合的破坏慢性疼痛 以及使用行为和神经影像措施的健康控制，其长期目标是改善 基于慢性疼痛的青少年的基于暴露的治疗方法。 AIM 1检查的采集和灭绝 恐惧在慢性疼痛且与疼痛相关的青少年中在行为和神经生物学上学习在行为和神经生物学上 恐惧和健康的控制，考虑父母的恐惧和回避行为的影响。目标2 通过破坏恐惧记忆的重新整合，检查了恐惧灭绝的增强。目前， 慢性疼痛的治疗是次优的。重大突破需要对密钥的机械理解 与疼痛相关功能障碍的过程。定义恐惧的行为和神经生物学机制 学习和灭绝将导致我们对持续疼痛的理解和治疗的进步 青少年。

项目成果

Amygdala functional connectivity mediates the association between catastrophizing and threat-safety learning in youth with chronic pain.

• DOI: 10.1097/j.pain.0000000000002410
• 发表时间: 2022-04-01
• 期刊: Pain
• 影响因子: 7.4
• 作者: Timmers I;López-Solà M;Heathcote LC;Heirich M;Rush GQ;Shear D;Borsook D;Simons LE
• 通讯作者: Simons LE

Altered anterior insula functional connectivity in adolescent and young women with endometriosis-associated pain: Pilot resting-state fMRI study.

• DOI: 10.1016/j.ejpn.2022.10.004
• 发表时间: 2022-11
• 期刊: EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY
• 影响因子: 3.1
• 作者: Szabo, Edina;Timmers, Inge;Borsook, David;Simons, Laura E.;Sieberg, Christine B.
• 通讯作者: Sieberg, Christine B.