Temporary persistence of conduction block after prolonged kilohertz frequency alternating current on rat sciatic nerve

Abstract

Objective: Application of kilohertz frequency alternating current (KHFAC) waveforms can result in nerve conduction block that is induced in less than a second. Conduction recovers within seconds when KHFAC is applied for about 5-10 min. This study investigated the effect of repeated and prolonged application of KHFAC on rat sciatic nerve with bipolar platinum electrodes.

Approach: Varying durations of KHFAC at signal amplitudes for conduction block with intervals of no stimulus were studied. Nerve conduction was monitored by recording peak Gastrocnemius muscle force utilizing stimulation electrodes proximal (PS) and distal (DS) to a blocking electrode. The PS signal traveled through the block zone on the nerve, while the DS went directly to the motor end-plate junction. The PS/DS force ratio provided a measure of conduction patency of the nerve in the block zone.

Main results: Conduction recovery times were found to be significantly affected by the cumulative duration of KHFAC application. Peak stimulated muscle force returned to pre-block levels immediately after cessation of KHFAC delivery when it was applied for less than about 15 min. They fell significantly but recovered to near pre-block levels for cumulative stimulus of 50 ± 20 min, for the tested On/Off times and frequencies. Conduction recovered in two phases, an initial fast one (60-80% recovery), followed by a slower phase. No permanent conduction block was seen at the end of the observation period during any experiment.

Significance: This carry-over block effect may be exploited to provide continuous conduction block in peripheral nerves without continuous application of KHFAC.

Figure 1

a. Schematic of the experimental set-up with proximal, distal and KHFAC electrodes. b. Left panel showing sample record of peak evoked muscle forces with proximal (PS) and distal (DS) stimulation. In each Off interval without KHFAC stimulus, PS/DS was determined by the ratio of each PS evoked peak force to the average DS evoked response in the same interval. c: Showing a schematic of reduction and recovery of PS/DS during an interval without KHFAC, after application of KHFAC (On, minutes). Phase I: fast recovery, Phase II: slow recovery.

Figure 2

Showing PS/DS during two experiments with repeated trains of KHAC at 10 kHz. During the Off intervals, PS and DS were applied to record muscle twitch force responses. Bar marks near baseline denote KHFAC On periods. Above: 5 minutes On with 5 minutes Off intervals. Reduction in PS/DS was significant (p<0.01) after 75 minutes of cumulative KHFAC. Below: 10 minutes On with 10 minutes Off intervals. Reduction in PS/DS was significant (p<0.01) after 70 minutes of cumulative KHFAC.

Figure 3

Study Set A. Mean (+/− 1 SD) of PS/DS at the start and end in an Off period without stimulus, after a duration of Cumulative KHFAC (in minutes) applied up to that time. Mean at start of recovery is at the end of a given period of cumulative KHFAC. The reduction in value below 1.0 is a measure of conduction loss. Mean at end of recovery is a measure of gain in conduction before the next KHFAC application. The * indicates the cumulative KHFAC after which there was a statistically significant reduction in the mean at start of recovery.

Figure 4

Study Set B. Mean (+/− 1 SD) of PS/DS at the start and end in an Off period without stimulus, after a duration of Cumulative KHFAC (in minutes) applied up to that time. Mean at start of recovery is at the end of a given period of cumulative KHFAC. The reduction in value below 1.0 is a measure of conduction loss. Mean at end of recovery is a measure of gain in conduction before KHFAC application in the next On period. The * indicates the cumulative KHFAC after which there was a statistically significant reduction in the mean at start of recovery.