Nest#4-Nerve Excitation Control Through AC Regulation (NECTAR)

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• 批准号: 10701822
• 负责人: Tina Louise Vrabec
• 金额: $ 89.48万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-10 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10701822
• 关键词: Action Potentials; Area; Arrhythmia; Autonomic nervous system; Bronchial Spasm; Charge; Chronic; Chronic Obstructive Pulmonary Disease; Communication; Communities; Complex; Data; Devices; Disease; Down-Regulation; Electric Stimulation; Electrodes; Ensure; Failure; Fiber; Frequencies; Future; Goals; Heart; Histologic; Implant; Injections; Knowledge; Licensing; Maps; Measurement; Measures; Medical; Muscle; Nerve; Nerve Block; Nervous System; Nervous System control; Neural Conduction; Nociception; Output; Physiologic pulse; Physiological; Procedures; Protocols documentation; Publishing; Ramp; Regulation; Reproducibility; Research; Research Personnel; Safety; Speed; Sphincter; System; Techniques; Testing; Therapeutic; Therapeutic Effect; Time; Translations; Width; Work; bioelectronics; chronic neuropathic pain; clinical application; in vivo; multimodality; neural; neuroregulation; open source; prevent; research study; spasticity; tool; urinary; voltage; web site

Control of physiological systems via the autonomic nervous system is often based on a baseline of tonic neural activity that is modulated to achieve a desired state. Electrical stimulation can be used to increase, or upregulate, this activity, but until recently, there was no reliable means to rapidly and reversibly decrease, or downregulate, this activity. The ability to downregulate, or completely block, neural activity could apply to a wide range of clinical applications and new treatments, including: downregulation of sympathetic drive to the heart for arrhythmias, block of bronchopulmonary parasympathetic nerves to reverse the bronchospasm in chronic obstructive pulmonary disease (COPD), block of nociceptive fibers to alleviate chronic neuropathic pain, and block of spastic urinary sphincter muscles to enable voiding, etc. Kilohertz frequency alternating current (KHFAC) has been demonstrated as a way to provide nerve block in a quick acting, titratable, and rapidly reversible manner. The goal of the NECTAR project is to create the tools necessary to allow researchers to incorporate reversible electrical nerve block via KHFAC into their research in a practical, effective, and safe manner. KHFAC nerve block has two key features that distinguish it from non-electrical nerve block. First, KHFAC nerve block occurs instantly. Second, KHFAC nerve block is fully and rapidly reversible. Unfortunately, research in the area of nerve block has been hampered by a lack of commercially available nerve block devices. Successful application of KHFAC block requires knowledge of the specific waveform parameters for effective and safe use of these waveforms in neural control. The therapeutic effect of KHFAC is complex and multimodal resulting in suboptimal results from improperly tuned waveform parameters. The contribution of the NECTAR project will be to provide two critical deliverables related to KHFAC block: 1) a fully featured device with reproducible outputs and 2) comprehensive mapping of the KHFAC parameter space. In aim one, a KHFAC module will be produced that will include many key features such as amplitude/ frequency ramping, validated outputs, DC offset mitigation, and charge injection capacity (CIC) electrode testing. In aim two, we will perform chronic in vivo studies to provide data that establishes the therapeutic window for KHFAC block with respect to frequency, amplitude, charge delivery, and duty cycle. These studies will involve both functional and histological metrics for safety and efficacy. Electrical block, when combined with electrical stimulation, can provide real-time control of neural activity, in which action potentials can be variably upregulated or downregulated as needed; a significant advantage for many bioelectronic applications. With the completion of Aims 1 and 2, the NECTAR project will enable the bioelectronic research community to rapidly proceed with incorporation of KHFAC electrical nerve block into their research studies.

通过自主神经系统控制生理系统，通常基于补品的基线 调节以达到预期状态的神经活动。电刺激可用于增加或 上调这项活动，但是直到最近，还没有可靠的手段来快速，可逆地减少或 下调，这项活动。下调或完全阻断神经活动的能力可能适用于宽阔的能力 临床应用和新治疗的范围，包括：下调交感神经驱动力的心脏 心律不齐，支气管肺副交感神经的块，以逆转慢性支气管痉挛 阻塞性肺疾病（COPD），伤害性纤维的块，以减轻慢性神经性疼痛和 痉挛性泌尿括约肌的块肌肉可以使排尿，等等。 已被证明是在快速表演，可滴定和迅速可逆的快速表演中提供神经阻滞的一种方式 方式。花蜜项目的目标是创建必要的工具，以允许研究人员合并 通过KHFAC以实用，有效和安全的方式通过KHFAC进行可逆的电神经阻滞。 KHFAC神经块具有两个关键特征，可将其与非电信神经阻滞区分开。首先，KHFAC 神经阻滞立即发生。其次，KHFAC神经阻滞是完全，迅速可逆的。不幸的是，研究 在神经阻滞区域中，由于缺乏市售的神经阻滞设备而受到阻碍。 成功应用KHFAC块需要了解特定波形参数才能有效 并安全地在神经控制中使用这些波形。 KHFAC的治疗作用是复杂的和多模式的 导致不当调谐波形参数的次优结果。花蜜的贡献 项目将提供与KHFAC块相关的两个关键可交付成果：1）一个完整的设备， 可再现的输出和2）KHFAC参数空间的综合映射。 在AIM上，将产生一个KHFAC模块，其中包括许多关键功能，例如振幅/ 频率升值，经过验证的输出，DC偏移缓解和电荷注入能力（CIC）电极测试。 在目标二，我们将进行慢性体内研究，以提供为建立治疗窗口的数据 KHFAC块相对于频率，振幅，充电和占空比。这些研究将涉及 功能性和组织学指标，以实现安全性和有效性。 当与电刺激结合使用时，电气块可以提供对神经活动的实时控制 根据需要，可以多样化上调或下调哪些动作电位；一个重要的优势 许多生物电子应用。随着AIM 1和2的完成，Nectar项目将使 生物电子研究界，将KHFAC电神经阻滞纳入其 研究。