Investigations into the Etiology of Phantom Limb Sensations and Phantom Limb Pain

幻肢感觉和幻肢疼痛的病因学研究

基本信息

批准号：
10630821
负责人：
ROBERT S WATERS
金额：
$ 52.22万
依托单位：
UNIVERSITY OF TENNESSEE HEALTH SCI CTR
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-17 至 2024-04-30
项目状态：
已结题

项目摘要

Project Abstract Major limb amputation affects millions of people worldwide. Following amputation, all most all patients have phantom limb sensations (PLS) and over 85% develop phantom limb pain (PLP). Despite its documented existence for several hundred years, the etiology of PLP remains unknown. The three principal theories are cortical reorganization, a mismatch between visual and proprioceptive feedback, and proprioceptive memory. Experimental evidence demonstrates that cortical maps representing a limb within sensorimotor cortex reorganize following limb amputation. A correlation exists between the amount of cortical reorganization in upper extremity amputees and the severity of PLP. We have recently demonstrated that mirror therapy can relieve PLP in unilateral lower extremity amputees, but the physiological basis remains unknown. Our principal hypothesis is that, rather than simple cortical reorganization, rapid, but reversible changes, in addition to delayed changes, occur in the cortical network connecting various brain regions, leading to the development of PLS and PLP. We will assess whether dynamic changes in connectivity following upper limb deafferentation and manifest as PLS or PLP with proprioceptive memories, what changes there are in cortical network connectivity (using fMRI) to assess changes in brain activation patterns before and after visual feedback from mirror therapy, and determine if differential mechanisms underlie rapid and delayed dynamic functional changes in cortical networks following permanent forelimb deafferentation (amputation or brachial plexus nerve cut) and transient inactivation (brachial plexus anesthesia) using a rodent model to mimic changes observed in humans. These studies will not only enable us to better understand the physiological basis of the interaction of the visual system, cortical reorganization and network connectivity, and the development of PLP but will also contribute to the development of a functional measure of the response of PLP to treatment and may result in the development of additional treatments for PLP for both female and male amputees.

项目摘要主要肢体截肢会影响全球数百万的人。截肢后，所有患者均具有幻影肢体感觉（PLS）和超过85％的幻影肢体疼痛（PLP）。尽管有记录 PLP的病因已经存在数百年了。这三个主要理论是皮质重组，视觉和本体感受反馈之间的不匹配以及本体感受记忆。实验证据表明，代表感觉运动皮质中肢体的皮质图肢体截肢后重组。在皮质重组量之间存在相关性上肢截肢者和PLP的严重程度。我们最近证明了镜像疗法可以在单侧下肢截肢术中缓解PLP，但生理基础仍然未知。我们的校长假设是，除了简单的皮质重组，而不是快速但可逆的变化延迟变化，发生在连接各个大脑区域的皮质网络中，导致 PLS和PLP。我们将评估上肢脱落后连通性的动态变化是否变化并表现为具有本体感受记忆的PLS或PLP，皮质网络中发生了什么变化连接性（使用fMRI）来评估视觉反馈前后的大脑激活模式的变化镜像疗法，并确定差异机制是否是快速和延迟动态功能的基础永久性前肢脱落后皮质网络的变化（截肢或臂神经切割）和瞬时灭活（臂丛神经麻醉）使用啮齿动物模型来模仿在中观察到的变化人类。这些研究不仅将使我们能够更好地了解相互作用的生理基础视觉系统，皮质重组和网络连接以及PLP的发展，但也将有助于开发PLP对治疗反应的功能度量，并可能导致开发针对女性和男性截肢者的PLP的其他治疗方法。