Emory University School of Medicine, Atlanta, GA, United States of America.
MetroHealth Medical Center, Cleveland, OH, United States of America.
J Neural Eng. 2021 Mar 22;18(4). doi: 10.1088/1741-2552/abebed.
Electrical nerve block offers the ability to immediately and reversibly block peripheral nerve conduction and would have applications in the emerging field of bioelectronics. Two modalities of electrical nerve block have been investigated-kilohertz frequency alternating current (KHFAC) and direct current (DC). KHFAC can be safely delivered with conventional electrodes, but has the disadvantage of having an onset response, which is a period of increased neural activation before block is established and currently limits clinical translation. DC has long been known to block neural conduction without an onset response but creates damaging reactive species. Typical electrodes can safely deliver DC for less than one second, but advances in high capacitance electrodes allow DC delivery up to 10 s without damage. The present work aimed to combine DC and KHFAC into a single waveform, named the combined reduced onset waveform (CROW), which can initiate block without an onset response while also maintaining safe block for long durations. This waveform consists of a short, DC pre-pulse before initiating KHFAC.Simulations of this novel waveform were carried out in the axonal simulation environment NEURON to test feasibility and gain insight into the mechanisms of action. Two sets of acute experiments were then conducted in adult Sprague-Dawley rats to determine the effectiveness of the waveform in mitigating the onset response.The CROW reduced the onset response bothand. The onset area was reduced by over 90% with the tested parameters in the acute experiments. The amplitude of the DC pulse was shown to be particularly important for effective onset mitigation, requiring amplitudes 6-8 times the DC block threshold.This waveform can reliably reduce the onset response due to KHFAC and could allow for wider clinical implementation of electrical nerve block.
电神经阻滞提供了立即和可逆地阻断周围神经传导的能力，并且在新兴的生物电子学领域有应用。已经研究了两种电神经阻滞模式——千赫兹交流电（KHFAC）和直流电（DC）。KHFAC 可以使用常规电极安全地输送，但它的缺点是有起始反应，即在建立阻滞之前神经激活增加的一段时间，目前限制了临床转化。直流电早已被发现可以在没有起始反应的情况下阻断神经传导，但会产生有害的反应性物质。典型的电极可以安全地输送直流电不到一秒钟，但高电容电极的进步允许直流电输送长达 10 秒而不会造成损害。本工作旨在将直流电和 KHFAC 组合成一种单一的波形，称为组合的减少起始波形（CROW），该波形可以在没有起始反应的情况下启动阻滞，同时还可以长时间保持安全的阻滞。该波形由在启动 KHFAC 之前的短的直流电预脉冲组成。这种新颖波形的模拟在神经元模拟环境 NEURON 中进行，以测试可行性并深入了解作用机制。然后在成年 Sprague-Dawley 大鼠中进行了两组急性实验，以确定该波形在减轻起始反应方面的有效性。CROW 减少了两种情况下的起始反应。在急性实验中，用测试参数，起始面积减少了 90%以上。实验表明，直流脉冲的幅度对于有效减轻起始反应特别重要，需要达到直流阻断阈值的 6-8 倍的幅度。这种波形可以可靠地减少由于 KHFAC 引起的起始反应，并且可以允许更广泛地实施电神经阻滞。
