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对儿童进行的影像学研究，这些研究表明我们有能力对复杂区域疼痛综合征 (CRPS) 儿科模型的功能和解剖学变化进行成像。 CRPS 可能会在四肢相对轻微的创伤后发生。患者通常会出现肢体疼痛和僵硬、过敏和功能丧失。然而，与成人 CRPS 不同的是，儿童 CRPS 通常会完全消退，从而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，即使肢体受到轻微创伤，随着时间的推移，也可能会导致儿科大脑发生显着的神经（即结构和功能）变化，并持续到恢复期和恢复期之后。这很可能是儿科 CRPS 的一个显着特征，也是本次调查的中心焦点。这项研究的首要目标是确定儿童大脑的这种变化是否是可逆的。如果是这样，这种生物过程在阐明成人 CRPS 和为这两种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，我们将在儿科 CRPS 患者（疼痛和早期无痛状态）的纵向研究以及康复 CRPS 患者和健康对照（症状恢复后长达 24 个月）的横断面研究中使用成像技术来研究神经可塑性。具体目标是（1）首先测量CRPS患者（14-16岁）在疼痛状态下大脑的功能（fMRI）变化，然后在早期恢复（3个月内）状态下，将这些变化与年龄/性别匹配的对照中注意到的变化进行比较； (2) 与年龄/性别匹配的对照组相比，确定 14-16 岁患有 CRPS 影响其腿部的疼痛和早期恢复状态的儿科患者皮质厚度和白质束（使用扩散张量成像 - DTI）变化的可塑性； (3) 在康复 CRPS 患者队列的横断面研究中，在康复后 6、12 和 24 个月时测量相同的功能（如目标 1）和解剖学变化（如目标 2）；我们将这些变化与年龄性别匹配的对照进行比较。每个目标都将测试与儿科 CRPS 人群发生的功能和解剖学变化相关的具体假设。 公共健康相关性：这一独特的多学科努力将通过以下方式与 NIH 疼痛联盟的更广泛目标相吻合：(1) 显着提高对成人和儿童 CRPS 病理生理学的了解； (2) 高度重视转化应用，从而实现更有效的治疗、消除不必要的疼痛、加速康复、缩短住院时间和降低住院费用，并提高生活质量。

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.