CNS Plasticity in Pediatric Complex Regional Pain Syndrome

描述(申请人提供)：这项建议是基于我们最近对儿童进行的成像研究，这些研究表明我们有能力在复杂区域疼痛综合征(CRPS)的儿科模型中成像功能和解剖变化。在四肢受到相对较小的创伤后，可能会发生CRPS。患者通常表现为四肢疼痛和僵硬、过敏和功能丧失。然而，与成人CRPS不同的是，儿童CRPS通常会完全消失，因此提供了一种独特的慢性疼痛逆转模型。我们的初步发现表明，即使是肢体的轻微创伤也可能导致儿童大脑随着时间的推移而发生显著的神经(即结构和功能)变化，一直持续到恢复期和恢复期之后。这很可能是儿科CRPS的一个显著特征，也是本次研究的中心焦点。这项研究的首要目标是确定儿童大脑的这种变化是否可逆；如果是，这一生物学过程在阐明成人CRP和为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，我们将在一项对儿童CRPS患者(疼痛和早期无痛状态)的纵向研究中，以及对康复CRPS患者和健康对照组(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。具体目的是(1)首先测量CRPS患者(14-16岁)在疼痛状态下的脑功能(FMRI)变化，然后在恢复早期(3个月内)将这些变化与年龄/性别匹配的对照组进行比较；(2)确定14-16岁CRPS患者在疼痛状态和早期恢复状态下与年龄/性别匹配的对照组的皮质厚度和白质束变化的可塑性；(3)对康复后6、12和24个月的CRPS患者进行横断面研究，测量相同的功能变化(与目标1相同)和解剖变化(与目标2相同)；我们将这些变化与年龄-性别匹配的对照组进行比较。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具体假设。 与公共健康相关：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)显著提高对成人和儿童CRP的病理生理学的洞察力；(2)特别强调转化性应用，从而导致更灵敏的治疗、消除不想要的疼痛、加速康复、更短和更低成本的住院治疗，以及提高生活质量。

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.