Safe Direct Current Stimulator (SDCS) technology for blocking chronicperipheral pain

用于缓解慢性外周疼痛的安全直流刺激器 (SDCS) 技术

基本信息

批准号：
10610959
负责人：
Gene Yevgeny Fridman
金额：
$ 53.46万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-15 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10610959
关键词：
Action Potentials Address Agonist Anesthesia procedures Animal Experiments Animal Model Animals Artificial Implants Behavior Behavioral Biological Caliber Charge Chronic Cochlear Implants Data Data Set Devices Effectiveness Electrodes Electronics Electrophysiology (science)Esthesia Fiber Future Goals Image Implant Injections Intervention Ion Channel Ion Channel Gating Lead Ligation Longevity Measurement Metals Methodology Methods Microfluidics Modeling Movement Mus Muscle Nerve Nerve Block Nervous System Neurons Nociception Nociceptors Pacemakers Pain Pain management Performance Peripheral Peripheral Nerves Phase Physiologic pulse Rattus Research Safety Sodium Channel Spinal Spinal Cord Spinal Ganglia Spinal nerve structure System Technology Testing Therapeutic Vertebral column Work antagonist awake behavioral study chronic pain chronic pain management deep brain stimulator design experimental study histological studies improved in vivo miniaturize myelination nerve injury neural neural prosthesis neuroregulation new technology pain inhibition pain model pain sensation pain signal painful neuropathy predictive modeling retina implantation sciatic nerve sex side effect spared nerve technology development voltage

项目摘要

Project Summary The central goal of this project is to advance the therapeutic applications and the potential for using ionic direct current to interact with the nervous system. Direct current (DC) compared to biphasic charge balanced pulses normally used by neural prostheses to interface to the nervous system, can more naturally control neural activity. Unlike biphasic current pulses used to excite neurons, DC can excite, inhibit, and modulate sensitivity of neurons. While DC can be used for short durations to interact with the nervous system, chronic use of this stimulation paradigm for implantable prosthetic applications has not been possible due to the DC’s inherent violation of the charge injection safety constraints at the metal electrode interfaces. New technology, safe direct current stimulation (SDCS) overcomes these constraints and opens an additional avenue for research into exciting possibilities of using DC to interface to the nervous system. We will optimize the use of ionic DC to improve the performance of chronic pain suppression. Chronic pain suppression requires inhibiting pain carrying neurons from conducting action potentials. We obtained preliminary data in an anesthetized rat model showing that safe DC neural block at the sciatic nerve could suppress pain signals from propagating to the spinal cord, but allow normal propagation of sensation and muscle movement. Here we propose to understand the mechanism behind safe DC modulation of pain signals through anesthetized mouse and rat experiments. We will conduct the behavioral experiments to understand the effectiveness of this technology for addressing chronic pain in an awake animal. We will also conduct histological studies to investigate the biological impact of the therapy. Finally, we will advance the SDCS technology by identifying and solving the key technical challenges with a miniaturized and implantable SDCS. Aim 1. Examine the mechanism of the iDC effect on suppression of nociceptive pain. Aim 2. Examine the effects and underlying mechanisms of iDC on neuropathic pain signals. Aim 3. Behavioral experiments to study iDC for inhibition of neuropathic pain. Aim 4. Implantable SDCS technology development.

项目概要该项目的中心目标是推进治疗应用和使用离子的潜力与双相电荷平衡相比，直流电与神经系统相互作用。神经假体通常使用脉冲来连接神经系统，可以更自然地控制神经与用于兴奋神经元的双相电流脉冲不同，直流电可以兴奋、抑制和调节敏感性。虽然 DC 可用于短期与神经系统相互作用，但长期使用它。由于 DC 固有的特性，植入式假肢应用的刺激范例一直不可能实现。突破金属电极界面电荷注入安全限制新技术，安全直接。电流刺激（SDCS）克服了这些限制，并为研究开辟了一条新途径使用 DC 与神经系统连接的令人兴奋的可能性。我们将优化离子 DC 的使用，以提高慢性疼痛抑制的性能。疼痛抑制需要抑制携带疼痛的神经元传导动作电位。麻醉大鼠模型的初步数据表明，安全的坐骨神经直流神经阻滞可以抑制疼痛信号传播到脊髓，但允许感觉和肌肉的正常传播移动。在这里，我们建议通过以下方式了解疼痛信号安全直流调制背后的机制：我们将进行麻醉小鼠和大鼠实验来了解。该技术对于解决清醒动物慢性疼痛的有效性我们还将进行组织学研究。最后，我们将通过研究来调查该疗法的生物学影响。通过小型化和植入式 SDCS 识别并解决关键技术挑战。目标 1. 检查 iDC 抑制伤害性疼痛的作用机制。目标 2. 检查 iDC 对神经性疼痛信号的影响和潜在机制。目标 3. 通过行为实验研究 iDC 抑制神经性疼痛的作用。目标 4. 植入式 SDCS 技术开发。