Intraspinal Microstimulation for Multi-modal Rehabilitation

多模式康复的椎管内微刺激

• 批准号: 10041057
• 负责人: Jacob Graves McPherson
• 金额: $ 34.42万
• 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/10041057
• 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）通常会导致运动障碍和神经性疼痛。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 加工。通常，病变下方的脊柱电路路径的神经传播太少， 而在病变下的疼痛途径中，有过多的，不适当的神经传播。 以前已经证明，少量电流直接传递到电机 脊髓的区域可以增加运动通路中的神经传播。这种类型的脊柱刺激 称为治疗性脊柱内微刺激。随着时间的流逝，脊柱内微刺激可以增强电动机 科学后的恢复。该提议的总体假设是运动内微刺激运动 还可以设计康复以减少脊柱疼痛途径的传播。如果得到确认，这可能会导致 在SCI后开发用于多模式康复的神经假体疗法。 该建议的主要目标是确定脊柱内微刺激的程度 减少脊柱疼痛途径中的神经传播。这些效果以前尚未表征。这是 知道，主要的微刺激会激活与非pain相关感觉途径的广泛网络 桥梁的脊髓运动区域和脊髓的疼痛处理区域。激活 该网络通过周围神经或脊柱表面刺激可以减少脊柱疼痛途径的传播。 该建议将确定脊柱内微刺激可以减轻疼痛的传播 通过激活该网络的路径。 该建议还将确定主要的微刺激是否促进了释放和/或使用 天然神经递质类别称为单胺。单胺具有独特的能力 同时减少脊柱疼痛途径的传播，同时增加脊髓电动机的传播 途径。利用单胺的神经元在整个由神经元网络中终止。 载体内微刺激。所有假设都将在用慢性运动的麻醉大鼠中在体内进行测试 不完整的SCI和无神经损伤的大鼠。两种男女的大鼠将包括在内。方法 包括电生理，计算，药理和生化分析的神经活动。 该提案将提高对脊柱内微刺激如何对高度影响的理解 互连的脊柱感觉运动网络。如果获得了对假设的支持，则该提案将有 还确定了一种新的神经假体疗法策略，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：与科学有关的非阿片类药物治疗 神经性疼痛和多模式康复。它也将克服临床可用的关键限制 脊柱刺激剂，该刺激器仅用于治疗运动或感觉障碍。