Intraspinal Microstimulation for Multi-modal Rehabilitation

多模式康复的椎管内微刺激

• 批准号: 10516936
• 负责人: Jacob Graves McPherson
• 金额: $ 6.3万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-15 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10516936
• 关键词: Address; Biochemical; Chronic; Clinical; Combined Modality Therapy; Development; Electrophysiology (science); Goals; Impairment; Individual; Lead; Lesion; Motor; Motor Pathways; Motor output; Nervous System Trauma; Neurons; Neurotransmitters; Pain; Pathway interactions; Peripheral Nerves; Pharmacology; Population; Public Health; Rattus; Rehabilitation therapy; Sensory; Spinal; Spinal Cord; Spinal cord injury; Spine pain; Surface; Synaptic Transmission; Therapeutic; Time; Work; design; in vivo evaluation; intraspinal microstimulation; monoamine; motor control; motor impairment; motor recovery; motor rehabilitation; multimodality; neuroprosthesis; non-opioid analgesic; pain perception; pain processing; painful neuropathy; relating to nervous system; sex; transmission process

Spinal cord injury (SCI) often results in motor impairments and neuropathic pain. These conditions are related to changes in neural activity in regions of the spinal cord that control motor output and sensory processing. Generally, there is too little neural transmission in spinal motor pathways below the lesion, whereas there is excessive, inappropriate neural transmission in pain pathways below the lesion. It has previously been shown that delivery of small amounts of electrical current directly to motor regions of the spinal cord can increase neural transmission in motor pathways. This type of spinal stimulation is called therapeutic intraspinal microstimulation. Over time, intraspinal microstimulation can enhance motor recovery after SCI. The overall hypothesis of this proposal is that intraspinal microstimulation for motor rehabilitation can also be designed to reduce transmission in spinal pain pathways. If confirmed, this could lead to development of neuroprosthetic therapies for multimodal rehabilitation after SCI. The primary goal of this proposal is to determine the extent to which intraspinal microstimulation can reduce neural transmission in spinal pain pathways. These effects have not previously been characterized. It is known that intraspinal microstimulation activates a widespread network of non-pain-related sensory pathways that bridge the motor regions of the spinal cord and the pain-processing regions of the spinal cord. Activation of this network by peripheral nerve or spinal surface stimulation can reduce transmission in spinal pain pathways. This proposal will determine the extent to which intraspinal microstimulation can reduce transmission in pain pathways through activation of this network. This proposal will also determine whether intraspinal microstimulation promotes release and/or use of a class of natural neurotransmitters known as the monoamines. Monoamines have the unique ability to simultaneously reduce transmission in spinal pain pathways while increasing transmission in spinal motor pathways. Neurons that utilize monoamines have terminations throughout the network of neurons activated by intraspinal microstimulation. All hypotheses will be tested in vivo in anesthetized rats with chronic, motor- incomplete SCI and in rats without neurological injury. Rats of both sexes will be included. The approach includes electrophysiological, computational, pharmacological and biochemical analyses of neural activity. This proposal will advance the understanding of how intraspinal microstimulation impacts highly interconnected spinal sensorimotor networks. If support for the hypotheses is obtained, this proposal will have also identified a new strategy for neuroprosthetic therapies to deliver multimodal rehabilitation benefits. This would address two critical unmet needs of the SCI population: non-opioid treatments for SCI-related neuropathic pain and multimodal rehabilitation. It would also overcome a key limitation of clinically available spinal stimulators, which are parameterized for treatment of motor or sensory impairments alone.

脊髓损伤(SCI)常导致运动障碍和神经病理性疼痛。这些条件是 与控制运动输出和感觉的脊髓区域的神经活动变化有关 正在处理。一般来说，损伤下方的脊髓运动通路中的神经传递太少， 而在损伤下方的疼痛通路中有过度的、不适当的神经传递。 此前已有研究表明，将少量电流直接输送到电机 脊髓的区域可以增加运动通路中的神经传递。这种类型的脊柱刺激 被称为治疗性椎管内微刺激。随着时间的推移，椎管内微刺激可以增强运动 脊髓损伤后的康复。这一建议的总体假设是椎管内微刺激对运动的影响 康复治疗也可以被设计成减少脊椎疼痛通路的传递。如果得到证实，这可能会导致 发展脊髓损伤后多模式康复的神经假体疗法。 该提案的主要目标是确定椎管内微刺激可以在多大程度上 减少脊椎疼痛通路中的神经传递。这些影响以前没有被描述过。它是 已知椎管内微刺激激活广泛的非疼痛相关感觉通路网络 它连接了脊髓的运动区和脊髓的疼痛处理区域。激活 这种通过刺激周围神经或脊柱表面形成的神经网络可以减少脊椎疼痛通路的传递。 这项建议将决定椎管内微刺激可以在多大程度上减少疼痛的传递。 通过激活这一网络的通路。 这项建议还将确定椎管内微刺激是否促进释放和/或使用 一类被称为单胺的天然神经递质。单胺类化合物具有独特的能力 同时减少脊椎疼痛通路的传递，同时增加脊髓运动的传递 小路。利用单胺的神经元在整个神经元网络中都有终末，激活的神经元网络 椎管内微刺激。所有假说都将在麻醉大鼠的体内进行测试，这些大鼠患有慢性运动障碍。 不完全性脊髓损伤和无神经损伤的大鼠。两性的老鼠都将被包括在内。该方法 包括神经活动的电生理、计算、药理学和生化分析。 这一建议将促进对椎管内微刺激如何产生高度影响的理解 相互连接的脊椎感觉运动网络。如果这些假设得到支持，这项提议将具有 还确定了神经假体疗法的新战略，以提供多模式康复益处。这 将解决脊髓损伤人群未得到满足的两个关键需求：脊髓损伤相关的非阿片类药物治疗 神经病理性疼痛和多模式康复。它还将克服临床可用的一个关键限制 脊柱刺激器，仅用于治疗运动或感觉障碍的参数设置。