Safe Direct Current Stimulator (SDCS) technology for blocking chronic peripheral pain

用于缓解慢性外周疼痛的安全直流刺激器 (SDCS) 技术

• 批准号: 9885600
• 负责人: Gene Yevgeny Fridman
• 金额: $ 54.18万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-15 至 2024-04-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9885600
• 关键词: Action Potentials; Address; Agonist; Animal Experiments; Animal Model; Animals; Behavior; Behavioral; Biological; Caliber; Cathodes; Charge; Chronic; Cochlear Implants; Data; Data Set; Devices; Effectiveness; Electrodes; Electronics; Electrophysiology (science); Esthesia; Fiber; Future; Goals; Image; Injections; Intervention; Ion Channel; Ion Channel Gating; Lead; Ligation; Longevity; Measurement; Metals; Methodology; Methods; Microfluidics; Modeling; Movement; Mus; Muscle; Nerve; Nerve Block; Nervous system structure; Neurons; Nociception; Pacemakers; Pain; Pain management; Performance; Peripheral; Peripheral Nerves; Physiologic pulse; Prosthesis; Rattus; Research; Safety; Sodium Channel; Spinal; Spinal Cord; Spinal Ganglia; Spinal nerve structure; System; Technology; Testing; Therapeutic; Work; awake; base; behavioral study; chronic pain; deep brain stimulator; design; experimental study; histological studies; improved; in vivo; miniaturize; myelination; nerve injury; neural prosthesis; neuroregulation; new technology; pain inhibition; pain model; pain sensation; pain signal; painful neuropathy; peripheral pain; predictive modeling; relating to nervous system; retina implantation; sciatic nerve; sex; side effect; spared nerve; technology development; voltage

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 直流电与神经系统相互作用。直流 (DC) 与双相充电平衡相比 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 活动。与用于激发神经元的双相电流脉冲不同，直流电可以激发、抑制和调节敏感性 神经元。虽然 DC 可以短期使用来与神经系统相互作用，但长期使用这种药物 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。 违反金属电极界面处的电荷注入安全约束。新技术，安全直达 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。慢性的 疼痛抑制需要抑制携带疼痛的神经元传导动作电位。我们得到了 麻醉大鼠模型的初步数据表明，坐骨神经处的安全直流神经阻滞可以 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： 麻醉小鼠和大鼠实验。我们将进行行为实验来了解 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检查 研究调查该疗法的生物学影响。最后，我们将通过以下方式推进 SDCS 技术： 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。