Reversible block of nerve conduction using low frequency alternating currents

项目摘要/摘要 人体内的器官系统受神经系统控制。慢性病和疾病可以改变 器官的设定点。生物电动药物的目的是通过影响这些设定值使其趋于正常 或者通过使用电刺激等技术来调节神经系统。几个世纪以来， 我们已经能够通过电刺激激活神经系统。然而，安全的方法 阻止或停止神经活动一直是我们所不能理解的。该项目旨在推进一种可逆减速的方法。 和/或停止神经传导以沉默或阻止正在进行的神经活动在神经中传播。这种技术， 所谓的低频交流电(LFAC)刺激包括应用低水平正弦 μAs的幅度在100‘S的电流，以及表面上频率在0.1100赫兹范围内的电流 神经束的神经束的或神经束内的LFAC代表了一种潜在的手段，可以即时、安全和 可逆地阻断神经活动。初步工作表明，波形先是减慢，然后完全 停止传导动作电位，而不在电流水平为 被认为长期使用是安全的。要了解LFAC阻塞的机制，还需要探索。 这些波形如何以及为什么会阻断神经传导。了解这一机制并在 模型可以更深入地了解如何将实现数据块和降低成本所需的当前级别降至最低 调整电极和波形以实现阻断所需的时间。这个项目的目的是1)描述 周围小神经束的参数空间LFAC阻滞，2)决定神经的疗效 LFAC块上的分束缩放，3)改进了硅内建模框架以准确描述LFAC 阻止。如果成功，这项研究将使研究能够具体确定LFAC的机制，以及 使其能够更广泛地用作神经调节工具，供临床医生/科学家用于开发新的 生物电药物，由神经科学家调节特定的路径，由康复从业者 改进功能性电刺激和治疗等技术。最终，这项工作可能会为 电疗慢性疾病的方法，包括过度活动的疼痛纤维引起的慢性疼痛 活动，过度活跃的肠道和膀胱，以改善功能，减少脊髓阵挛-紧张性痉挛 受伤了。

PROJECT SUMMARY / ABSTRACT Organ systems in the body are under the control of the nervous system. Chronic disease and illness can alter the set point of the organ. Bioelectric medicines aim to adjust these set points towards normality by influencing or modulating the nervous system through the use of techniques such as electrical stimulation. For centuries, we have been able to activate the nervous system using electrical stimulation. However, methods to safely block or stop nerve activity have eluded us. This project aims to advance a method that reversibly slows and / or stops nerve conduction to silence or block ongoing nerve activity traveling in the nerve. The technique, named low frequency alternating current (LFAC) stimulation involves the application of low level sinusoidal currents with amplitudes in the 100’s of μAs, and frequencies in the range of 0.1 – 100 Hz either on the surface of or within the nerve bundle. LFAC represents a potential means to instantaneously, safely and reversibly block nerve activity. Preliminary work indicates that the waveform slows and then completely stops conducting action potentials without onset activation at current levels that are within currents that are considered safe for long term use. The mechanism of LFAC block needs exploration in order to understand how and why these waveforms block nerve conduction. Understanding the mechanism and distilling them in a model can provide greater insight into how to minimize the current levels needed to achieve block and reduce the time needed to tune the electrode and waveform to achieve block. This project aims to 1) Characterize the parameter space LFAC block for small peripheral nerve fascicles, 2) Determine the effect of nerve fascicle scaling on LFAC block, 3) Refine an in-silico modeling framework to accurately describe LFAC block. If successful, the research will enable research to specifically identify the mechanism of LFAC, and enable its broader use as a neuromodulatory tool for use by clinicians/scientists for developing novel bioelectric medicines, by neuroscientists to condition specific pathways, and by rehabilitation practitioners to improve techniques such as functional electrical stimulation and therapies. Ultimately, this work could pave the way towards electrical therapies of chronic conditions that include chronic pain from overactive pain fiber activity, overactive bowel and bladder to improve function, and reduce clonic-tonic spasticity in the spinal cord injured.