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

• 批准号: 10005412
• 负责人: ROBERT S WATERS
• 金额: $ 56.15万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/10005412
• 关键词: Affect; Amputation; Amputees; Anesthesia procedures; Animal Model; Brachial plexus structure; Brain; Brain region; Clinical; Deafferentation procedure; Development; Esthesia; Etiology; Feedback; Female; Forelimb; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Human; Investigation; Limb structure; Lower Extremity; Measures; Memory; Modeling; Nerve Plexus; Paralysed; Patients; Pattern; Phantom Limb; Phantom Limb Pain; Physiological; Rodent Model; Severities; Testing; Upper Extremity; Veterans; Visual; Visual system structure; cortex mapping; limb amputation; male; military service; response; service member; theories; visual feedback

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 全世界有数百万人受到严重截肢的影响。截肢后，几乎所有患者都有 幻肢感觉（PLS）和超过85%的发展幻肢痛（PLP）。尽管它的记录 PLP存在数百年，其病因仍然未知。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，在感觉运动皮层中， 在截肢后重新组织。大脑皮层重组的数量与大脑皮层的活动量之间存在着相关性。 上肢截肢者和PLP的严重程度。我们最近已经证明镜子疗法可以 缓解单侧下肢截肢者的PLP，但生理基础尚不清楚。我们的主要 假设是，除了简单的皮质重组，快速但可逆的变化， 延迟的变化，发生在连接不同大脑区域的皮质网络中，导致 PLS和PLP。我们将评估上肢传入神经阻滞后连接的动态变化是否 并表现为PLS或PLP的本体感受记忆，在皮层网络中有什么变化 连接（使用fMRI）来评估视觉反馈前后大脑激活模式的变化， 镜像治疗，并确定是否差异机制的基础上快速和延迟的动态功能 永久性前肢传入神经切断（截肢或臂丛神经）后皮质网络的变化 切割）和短暂失活（臂丛神经麻醉），使用啮齿动物模型模拟在 人类这些研究不仅使我们能够更好地了解 视觉系统，皮层重组和网络连接，以及PLP的发展，但也将 有助于开发PLP对治疗反应的功能性测量，并可能导致 为女性和男性截肢者开发更多的PLP治疗方法。