CNS Plasticity in Pediatric Complex Regional Pain Syndrome

描述（由申请人提供）：本提案基于我们最近在儿童中进行的成像研究，这些研究显示我们能够对复杂区域疼痛综合征（CRPS）儿科模型中的功能和解剖学变化进行成像。CRPS可能在肢体相对较小的创伤后发展。患者通常表现为肢体疼痛和僵硬、超敏反应和功能丧失。然而，与成人CRPS不同，儿童CRPS通常会完全消退，因此提供了一种独特的慢性疼痛逆转模型。我们的初步研究结果表明，即使是肢体的轻微创伤也可能导致严重的神经损伤（即，结构和功能）的变化，并持续到恢复期之后。这很可能是儿科CRPS的一个显著特征，并作为本研究的中心焦点。这项研究的总体目标是确定儿童大脑的这种变化是否是可逆的;如果是，这种生物学过程在阐明成人CRPS和为这两个人群开发更有效的治疗方法方面可能发挥什么作用。在此背景下，我们将在儿童CRPS患者（疼痛和早期无痛状态）的纵向研究中使用成像技术研究神经可塑性，并在康复的CRPS患者和健康对照（症状恢复后长达24个月）的横断面研究中进行研究。具体目的是：（1）测量CRPS患者脑功能（fMRI）变化（14-16岁）首先是在痛苦的状态下，然后，在早期恢复期间（3个月内）状态，将这些变化与年龄/性别匹配的对照组中观察到的变化进行比较;（2）明确皮质厚度和白色束变化的可塑性（使用弥散张量成像- DTI）在14-16岁的CRPS儿科患者中，与年龄/性别匹配的对照组相比，在他们的疼痛和早期恢复状态期间影响他们的腿;（3）在CRPS患者恢复后6个月、12个月和24个月时，在CRPS恢复患者队列的横断面研究中测量相同的功能（如目标1中所述）和解剖学变化（如目标2中所述）;我们将这些变化与年龄-性别匹配的对照进行比较。每个目标将测试与儿童CRPS人群中发生的功能和解剖结构变化相关的特定假设。

DESCRIPTION (provided by applicant): This proposal is based on our recent imaging studies in children that show our ability to image functional and anatomical changes in a pediatric model of Complex Regional Pain Syndrome (CRPS). CRPS may develop following relatively minor trauma to the limbs. Patients typically present with limb pain and stiffness, hypersensitivity, and functional loss. Unlike adult CRPS, however, pediatric CRPS will usually resolve completely and thus provides a unique model of chronic pain reversal. Our preliminary findings suggest that even minor trauma to a limb may result in significant neural (i.e., structural and functional) changes in the pediatric brain over time, persisting well into and beyond the recovery period. This may well be a distinctive feature of pediatric CRPS and serves as a central focus of this investigation. The overarching goal of the research proposed is to determine whether such changes to the pediatric brain are reversible; and if so, what role this biological process may play in elucidating adult CRPS and in developing more effective therapies for both populations. Against this backdrop, we will investigate neural plasticity using imaging techniques in a longitudinal study of pediatric CRPS patients (in pain and in early pain-free states) and in a cross-sectional study of recovered CRPS patients and healthy controls (up to 24 months following symptomatic recovery). The specific aims are (1) To measure the functional (fMRI) changes in the brains of CRPS patients (ages 14-16) first during the painful state, and then, during the early recovery (within 3 months) state, comparing these changes to those noted in age/gender matched controls; (2) To define plasticity of changes in cortical thickness and white matter tracts (using diffusor tensor imaging - DTI) in pediatric patients ages 14-16 with CRPS affecting their leg during their painful and early recovered states, vs. age/gender matched controls; (3) To measure the same functional (as in Aim 1) and anatomical changes (as in Aim 2) in a cross sectional study of cohorts of recovered CRPS patients at 6, 12 and 24 months following their recovery; we will compare these changes with age- gender matched controls. Each aim will test specific hypotheses related to the functional and anatomical changes that take place in pediatric CRPS population.