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

项目摘要 大腿截肢影响着全球数百万人。截肢后，大多数ALL患者都有 幻肢感觉(PLS)和超过85%的人发展为幻肢疼痛(PLP)。尽管有记录在案 PLP存在了几百年，其病因仍不清楚。三个主要的理论是 皮层重组，视觉和本体感觉反馈之间的不匹配，以及本体感觉记忆。 实验证据表明，在感觉运动皮质内代表肢体的皮质映射 截肢后的重组。在大脑皮质重组量之间存在相关性 上肢截肢者与PLP的严重程度。我们最近证明了镜面疗法可以 缓解单侧下肢截肢者的PLP，但其生理基础尚不清楚。我们的委托人 假说是，不是简单的皮质重组，而是快速但可逆的变化，除了 延迟性变化，发生在连接大脑不同区域的皮质网络中，导致 请和PLP。我们将评估上肢去传入后连接性的动态变化 并表现为PLS或PLP伴本体感觉记忆，大脑皮层网络有哪些变化 连接性(使用功能磁共振成像)评估视觉反馈前后大脑激活模式的变化 镜像治疗，并确定快速和延迟动力功能的不同机制 永久性前肢去传入(截肢或臂丛神经)后皮质网络的变化 使用啮齿动物模型来模拟观察到的变化 人类。这些研究不仅使我们能够更好地了解人与人之间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 有助于制定PLP对治疗的反应的功能性衡量标准，并可能导致 为女性和男性截肢者开发PLP的额外治疗方法。

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.