Reversible block of nerve conduction using low frequency alternating currents

项目摘要/摘要

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.