Reduction of the onset response in high frequency nerve block

Many diseases are characterized by undesired or pathological neural activity. The local delivery of high frequency currents has been shown to be an effective method for blocking neural conduction in peripheral nerves and may provide a therapy for these conditions. However, this type of nerve block produces a finite burst of neuronal firing (several seconds) called the onset response when the high frequency currents are first delivered to the nerve. When the onset response is complete, the nerve is transitioned to a state of conduction block that can be maintained indefinitely with continued delivery of the high frequency alternating current. Reduction or elimination of the onset response is very important to moving this type of nerve block into clinical applications since the onset response is likely to result in undesired muscle contraction and pain. This dissertation presents studies that show that this onset response can be reduced to hundreds of milliseconds or less in many cases by choosing the proper combination of electrode geometry and high frequency waveform amplitude. The onset response can be completely eliminated with the delivery of a direct current block through a separate blocking electrode. However, this direct current block is not safe for the durations required for blockade of the onset response with the electrodes used in this study. Preliminary results suggest that it may be possible to safely block the entire onset response using direct currents delivered using a different electrode technology or with direct nerve cooling. This dissertation also presents studies showing that the minimal high frequency current amplitude required to achieve block (block threshold) is a function, in part, of the electrode geometry. A biophysical explanation for the relationship between block threshold and electrode geometry is proposed based upon computer simulation of single axon fibers. High frequency nerve block was also found to be possible using an intrafascicular electrode. This document provides guidance for selection of a high frequency block electrode based on application, optimization of block threshold and reduction of onset response.