CNS Plasticity in Pediatric Complex Regional Pain Syndrome

描述（由申请人提供）：该提案基于我们最近在儿童中进行的影像学研究，这些研究表明我们有能力对复杂局部疼痛综合征（CRPS）的儿童模型进行功能和解剖变化的成像。CRPS可能发生在肢体相对较小的创伤之后。患者通常表现为肢体疼痛和僵硬、过敏和功能丧失。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，随着时间的推移，即使是肢体的轻微创伤也可能导致儿童大脑中显著的神经（即结构和功能）变化，这种变化会持续到恢复期之后。这可能是儿童CRPS的一个显著特征，也是本研究的中心焦点。这项研究提出的首要目标是确定儿童大脑的这种变化是否可逆；如果是这样，这个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，我们将利用成像技术对儿童CRPS患者（疼痛和早期无痛状态）进行纵向研究，并对康复的CRPS患者和健康对照（症状恢复后24个月）进行横断面研究，研究神经可塑性。具体目的是：(1)首先测量14-16岁CRPS患者在疼痛状态，然后在恢复早期（3个月内）状态下的大脑功能（fMRI）变化，并将这些变化与年龄/性别匹配的对照组进行比较；(2)利用弥散张量成像（diffusion tensor imaging - DTI），确定14-16岁CRPS患儿在疼痛和早期康复状态下，与年龄/性别匹配的对照组相比，皮质厚度和白质束变化的可塑性；(3)在康复后6个月、12个月和24个月对康复的CRPS患者进行横断面研究，测量相同的功能（如目的1）和解剖变化（如目的2）；我们将把这些变化与年龄性别匹配的对照进行比较。每个目标都将测试与儿科CRPS人群中发生的功能和解剖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. PUBLIC HEALTH RELEVANCE: This unique multidisciplinary effort will dovetail with the broader objectives of the NIH Pain Consortium by (1) significantly improving insights into the pathophysiology of both adult and pediatric CRPS; and (2) placing critical emphasis on translational applications leading to more responsive treatments, the elimination of unwanted pain, accelerated recoveries, shorter and less costly hospitalizations, and enhanced quality of life.