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紧张性的基线 被调节以达到期望状态的神经活动。电刺激可用于增加，或 上调，这种活动，但直到最近，没有可靠的手段来快速和可逆地减少，或 下调，这一活动。下调或完全阻断神经活动的能力可以广泛应用于 一系列的临床应用和新的治疗方法，包括：下调交感神经驱动心脏， 心律失常，支气管肺副交感神经阻滞，以扭转慢性支气管痉挛 阻塞性肺病（COPD）、阻断伤害性纤维以缓解慢性神经性疼痛，以及 阻断痉挛的尿道括约肌，使其能够排尿等。千赫频率交流电（KHFAC） 已经被证明是一种以快速作用、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，使研究人员能够将 可逆性电神经阻滞通过KHFAC以实用，有效和安全的方式进入他们的研究。 KHFAC神经阻滞有两个关键特征将其与非电神经阻滞区分开来。第一，KHFAC 神经阻滞立即发生。第二，KHFAC神经阻滞是完全和快速可逆的。不幸的是，研究 在神经阻滞领域中，由于缺乏市售的神经阻滞装置而受到阻碍。 KHFAC块的成功应用需要了解特定的波形参数，以便有效地 以及这些波形在神经控制中的安全使用。KHFAC的治疗效果是复杂的和多模式的 从而导致不适当调谐的波形参数的次优结果。NECTAR的贡献 该项目将提供两个关键的可交付成果有关KHFAC块：1）一个功能齐全的设备， 可再现的输出和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特征，如振幅/ 频率斜坡、经验证的输出、DC偏移缓解和电荷注入容量（CIC）电极测试。 在第二个目标中，我们将进行慢性体内研究，以提供建立治疗窗口的数据， KHFAC块相对于频率、振幅、电荷输送和占空比。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，当与电刺激结合时，可以提供对神经活动的实时控制， 其动作电位可以根据需要被上调或下调; 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进行合并KHFAC电神经阻滞到他们的 调查研究。