Reversible block of nerve conduction using low frequency alternating currents

项目概要/摘要 人体的器官系统是由神经系统控制的。慢性病和疾病可以改变 器官的设定点。生物电药物的目的是通过影响这些设定点来调整这些设定点，使其趋于正常。 或者通过使用诸如电刺激的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来激活神经系统。然而，安全地 阻止或停止神经活动的方法该项目旨在推进一种方法， 和/或停止神经传导以沉默或阻断在神经中行进的正在进行的神经活动。技术， 一种称为低频交流电（LFAC）刺激的方法涉及应用低电平正弦 电流的振幅在100 μ A，频率在0.1 - 100 Hz的范围内， 属于或在神经束内。LFAC代表了一种潜在的手段， 可逆地阻断神经活动。初步工作表明，波形变慢，然后完全 停止传导动作电位，而在电流水平下没有起始激活， 长期使用安全。LFAC阻滞的机制需要探索，以了解 这些波形是如何以及为什么阻断神经传导的了解其机制并将其提取到 模型可以更深入地了解如何最大限度地减少实现阻断和减少所需的电流水平 调整电极和波形以实现阻断所需的时间。本项目旨在：1）描述 参数空间LFAC阻滞用于小的周围神经束，2）确定神经效应 LFAC块上的分束缩放，3）完善计算机模拟建模框架以准确描述LFAC 块如果成功，该研究将使研究能够具体确定LFAC的机制， 使其能够更广泛地用作临床医生/科学家用于开发新的 生物电药物，神经科学家调节特定的通路，康复医生， 改进技术，如功能性电刺激和治疗。最终，这项工作可以铺平道路， 对慢性疾病的电疗法的方法，包括来自过度活跃的疼痛纤维的慢性疼痛 活动，过度活跃的肠道和膀胱，以改善功能，并减少脊髓的阵挛性强直性痉挛 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.