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.

通过自主神经系统对生理系统的控制通常基于强直的基线 被调节以达到所需状态的神经活动。电刺激可用于增加，或 上调这种活动，但直到最近，还没有可靠的方法来快速和可逆地减少，或者 下调此活动。下调或完全阻断神经活动的能力可以广泛应用于 一系列临床应用和新疗法，包括： 下调心脏交感神经驱动 心律失常，阻断支气管肺副交感神经以逆转慢性支气管痉挛 阻塞性肺病（COPD），阻断伤害性纤维以减轻慢性神经性疼痛，以及 阻断痉挛的尿道括约肌以实现排尿等。千赫兹频率交流电 (KHFAC) 已被证明是一种以快速、可滴定和快速可逆的方式提供神经阻滞的方法 方式。 NECTAR 项目的目标是创建必要的工具，让研究人员能够将 通过 KHFAC 将可逆性电神经阻滞以实用、有效和安全的方式纳入他们的研究中。 KHFAC 神经阻滞有两个区别于非电神经阻滞的关键特征。首先，KHFAC 神经阻滞立即发生。其次，KHFAC 神经阻滞是完全且快速可逆的。不幸的是，研究 由于缺乏市售神经阻滞设备，神经阻滞领域的研究受到阻碍。 KHFAC 模块的成功应用需要了解特定波形参数才能有效 以及在神经控制中安全使用这些波形。 KHFAC 的治疗作用是复杂的、多模式的 波形参数调整不当会导致结果不理想。 NECTAR 的贡献 该项目将提供与 KHFAC 块相关的两个关键交付成果：1）功能齐全的设备， 可重复的输出和 2) KHFAC 参数空间的全面映射。 在目标一中，将生产一个 KHFAC 模块，该模块将包括许多关键功能，例如幅度/ 频率斜坡、验证输出、直流偏移缓解和电荷注入容量 (CIC) 电极测试。 在目标二中，我们将进行长期体内研究，以提供建立治疗窗口的数据 KHFAC 块涉及频率、幅度、电荷传输和占空比。这些研究将涉及 安全性和有效性的功能和组织学指标。 电阻滞与电刺激相结合，可以实时控制神经活动， 哪些动作电位可以根据需要进行不同程度的上调或下调；的显着优势 许多生物电子应用。随着目标 1 和 2 的完成，NECTAR 项目将使 生物电子研究界迅速着手将 KHFAC 电神经阻滞纳入其研究中 研究。