Intraspinal Microstimulation for Multi-modal Rehabilitation

多模式康复的椎管内微刺激

• 批准号: 10436138
• 负责人: Jacob Graves McPherson
• 金额: $ 32.39万
• 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 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10436138
• 关键词: Address; Animal Model; Animals; Axon; Biochemical; Chronic; Clinical; Combined Modality Therapy; Data; Development; Dorsal; Drug Kinetics; Electrophysiology (science); Frequencies; Goals; Half-Life; High Pressure Liquid Chromatography; Hindlimb; Horns; Hyperreflexia; Impairment; Implant; Individual; Interneurons; Investigation; Lead; Lesion; Location; Mechanical Stimulation; Methods; Microelectrodes; Motor; Motor Pathways; Motor output; Muscle; Nervous System Trauma; Neurons; Neurotransmitters; Nociception; Norepinephrine; Outcome Measure; Pain; Pathologic; Pathway interactions; Peripheral; Peripheral Nerves; Pharmaceutical Preparations; Pharmacology; Physiologic pulse; Population; Protocols documentation; Public Health; Rattus; Recovery; Rehabilitation therapy; Sensory; Serotonin; Spinal; Spinal Anesthesia; Spinal Cord; Spinal cord injury; Spine pain; Surface; Synaptic Transmission; Therapeutic; Time; Work; base; cohort; design; dorsal horn; experimental study; in vivo evaluation; intraspinal microstimulation; monoamine; motor control; motor impairment; motor recovery; motor rehabilitation; multimodality; neuroprosthesis; neuroregulation; non-opioid analgesic; noradrenergic; novel; pain perception; pain processing; pain reduction; painful neuropathy; pre-clinical therapy; primary outcome; receptive field; receptor; recruit; relating to nervous system; response; secondary outcome; sensory feedback; sex; theories; 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性疼痛。这些条件 与控制运动输出和感觉的脊髓区域的神经活动变化有关 处理.一般来说，在病变下方的脊髓运动通路中神经传递太少， 而在病变下方的疼痛通路中存在过度的、不适当的神经传递。 先前已经表明，将少量电流直接输送到电动机 脊髓区域可以增加运动通路中的神经传递。这种脊髓刺激 叫做治疗性脊柱内微刺激。随着时间的推移，脊柱内微刺激可以增强运动神经元的功能。 SCI后的康复这一建议的总体假设是，脊髓内微刺激运动 康复也可以被设计为减少脊柱疼痛路径中的传递。如果得到证实， 发展神经假体治疗用于SCI后的多模式康复。 这项建议的主要目的是确定椎管内微刺激能在多大程度上 减少脊髓疼痛通路中的神经传递。这些影响以前没有被描述过。是 已知椎管内微刺激激活了广泛的非疼痛相关感觉通路网络 连接脊髓的运动区和脊髓的疼痛处理区。激活 这种网络通过外周神经或脊髓表面刺激可以减少脊髓疼痛通路中的传递。 这项提议将确定椎管内微刺激可以在多大程度上减少疼痛的传播 通过激活这个网络的途径。 该提案还将确定椎管内微刺激是否促进神经元的释放和/或使用。 一种天然的神经递质，称为单胺。单胺具有独特的能力， 同时减少脊柱疼痛路径中传递，同时增加脊柱运动中的传递 途径。利用单胺的神经元在整个神经元网络中具有终止，所述神经元网络由 椎管内微刺激所有假设将在患有慢性、运动性- 不完全性SCI和无神经损伤的大鼠。将纳入两种性别的大鼠。的方法 包括神经活动的电生理学、计算、药理学和生物化学分析。 该建议将促进对椎管内微刺激如何高度影响 相互连接的脊髓感觉运动网络。如果这些假设得到支持，这一提议将具有 还确定了神经假体治疗的新策略，以提供多模式康复益处。这 将解决SCI人群的两个关键未满足的需求：SCI相关的非阿片类药物治疗 神经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， 脊髓刺激器，其被参数化以单独治疗运动或感觉障碍。