Neurophysiology of Pain in Children with Cerebral Palsy

脑瘫儿童疼痛的神经生理学

• 批准号: 9903413
• 负责人: Max J Kurz
• 金额: $ 12.88万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2021-01-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9903413
• 关键词: Area; Brain; Brain Injuries; Brain imaging; Cerebral Palsy; Child; Childhood; Chronic; Clinic; Clinical; Clinical Trials; Complex; Consensus; Contracture; Development; Developmental Disabilities; Diagnosis; Economic Burden; Esthesia; Future; Goals; Hand; Intervention; Knowledge; Lead; Link; Lower Extremity; Magnetoencephalography; Mainstreaming; Methods; Motor; Muscle; Musculoskeletal; Musculoskeletal Pain; Musculoskeletal System; Neurologic; Neuronal Plasticity; Nociceptors; Operative Surgical Procedures; Pain; Pain Clinics; Pain Nature; Pain management; Patient Self-Report; Peripheral; Persistent pain; Physical therapy; Physiology; Population; Prevalence; Prevention and Treatment Evaluation; Reporting; Research; Rewards; Severities; Societies; Solid; Somatosensory Cortex; Source; Stretching; Structure; Testing; Time Series Analysis; Toxin; Treatment Protocols; Uncertainty; United States; Upper Extremity; Work; central pain; chronic musculoskeletal pain; chronic pain; cost; daily pain; disorder prevention; experience; foot; high risk; image reconstruction; imaging program; insight; neurophysiology; novel; pain perception; pain receptor; pain sensation; pain symptom; programs; receptor; relating to nervous system; response; rho; somatosensory; spasticity; treatment strategy

PROJECT SUMMARY/ABSTRACT Cerebral palsy (CP) is one of the most prevalent and costly pediatric neurologic conditions diagnosed in the United States. Although the brain injuries seen in these children are non-progressive, they often instigate a cascade of structural (i.e., boney malalignments, muscular contractures) and functional (i.e., co-contractions, spasticity) abnormalities within the musculoskeletal system that can become worse throughout development. These secondary changes are presumed to be primarily responsible for the chronic musculoskeletal pain that is seen in a large percentage of children with CP. However, currently there is a major lack of knowledge in this area, especially in regard to the neurophysiological mechanisms of the persistent pain, as most studies to date have focused on quantifying the prevalence of pain symptoms and not the underlying physiology. Without this critical information, the prevention, treatment and evaluation of the chronic musculoskeletal pain will not advance. Our extensive magnetoencephalographic (MEG) brain imaging program has identified that the early brain insults experienced by children with CP result in aberrant processing of the peripheral sensations by the somatosensory cortices. Recently, we have extended these results by showing that children with CP who have more abnormal somatosensory cortical oscillations following peripheral stimulation of the feet, also have higher reported pain. This relationship implies that there might be a fundamental link between the integrity of somatosensory cortical processing and the pain perceptions of children with CP. The goal of this proposal is to test our scientific premise that the disturbed somatosensory neural connections, potentially arising from maladaptive neuroplastic changes following early brain injuries, are altered in children with CP and that this leads to heightened activity in the pain perception network and chronic pain. Our approach is of “high risk”, but has the potential to be remarkably “rewarding,” as it may lead to novel insights and a paradigm shift in our understanding of pain perception in children with CP. The Specific Aims of this proposal will (1) demonstrate that the strength of somatosensory cortical oscillations following peripheral stimulation of the mechano- and nociceptors of the feet and hands will scale with a child’s perceived pain levels, and (2) determine if the strength of somatosensory cortical oscillations following peripheral stimulation are differentially altered in children with CP who have low versus high pain levels, and whether both groups differ from typically-developing (TD) children. Briefly, our study will use MEG, advanced image reconstruction methods, and time series analysis to quantify the strength of somatosensory cortical oscillations following stimulation of peripheral mechano- and nociceptors in TD children, and children who have spastic diplegic CP and different pain levels (i.e., severity). Achieving our Aims will provide substantial insight on the neural basis of chronic pain in children with CP, and may spark a paradigm shift in the mainstream treatment and assessment of musculoskeletal pain in this population.

项目摘要/摘要 脑瘫（CP）是最普遍，最昂贵的儿科神经系统疾病之一 美国。尽管在这些孩子中看到的脑损伤是非促进的，但他们经常会激发 结构性级联（即骨差，肌肉闭合）和功能（即共缩， 肌肉骨骼系统中的痉挛异常，在整个发育过程中可能会变得更糟。 这些次要变化被提出为主要负责慢性肌肉骨骼疼痛 在很大一部分患有CP的儿童中可见。但是，目前在这方面缺乏知识 区域，特别是关于持续疼痛的神经生理机制，因为大多数研究迄今为止的研究 专注于量化疼痛症状的患病率，而不是潜在的生理学。没有这个 关键信息，慢性肌肉骨骼疼痛的预防，治疗和评估不会促进。 我们广泛的磁脑摄影（MEG）脑成像程序已经确定了早期的大脑感染 由CP的儿童经历导致体感觉对周围感觉的异常处理 皮层。最近，我们通过表明患有更多异常的儿童来扩展这些结果 脚外周刺激后的体感觉皮质振荡也有更高的报道疼痛。 这种关系意味着体感的完整性之间可能存在基本联系 CP儿童的皮质加工和疼痛感。该提议的目的是测试我们 科学的前提是，受干扰的体感中性连接可能是由于适应不良而引起的 早期脑损伤后的神经塑性变化改变了CP儿童，这导致 疼痛感知网络和慢性疼痛的活动增加。我们的方法是“高风险”，但有 有可能“有益”的潜力，因为它可能导致新的见解和我们的理解范式转变 CP儿童的疼痛感。该提议的具体目的（1）证明了力量 在外周刺激机械和伤害感受器后，体感的皮质振荡 脚和手会随着孩子的感知疼痛水平而缩放，（2）确定体感的强度是否 CP儿童的外周刺激后的皮质振荡有所不同 与高疼痛水平相比，两组是否与典型的发展（TD）儿童有所不同。简而言之，我们的研究 将使用MEG，高级图像重建方法和时间序列分析来量化 刺激TD儿童外周手机和伤害感受器后的体感皮质振荡， 以及具有痉挛性Dipygic CP和不同疼痛水平（即严重程度）的儿童。实现我们的目标将提供 对CP儿童慢性疼痛的神经元基础的实质性见解，并可能引发范式转变 该人群中肌肉骨骼疼痛的主流治疗和评估。