Reversible Nerve Conduction Block Using Kilohertz Frequency Alternating Current

Abstract

Objectives The features and clinical applications of balanced-charge kilohertz frequency alternating currents (KHFAC) are reviewed. Preclinical studies of KHFAC block have demonstrated that it can produce an extremely rapid and reversible block of nerve conduction. Recent systematic analysis and experimentation utilizing KHFAC block has resulted in a significant increase in interest in KHFAC block, both scientifically and clinically. Materials and Methods We review the history and characteristics of KHFAC block, the methods used to investigate this type of block, the experimental evaluation of block, and the electrical parameters and electrode designs needed to achieve successful block. We then analyze the existing clinical applications of high frequency currents, comparing the early results with the known features of KHFAC block. Results Although many features of KHFAC block have been characterized, there is still much that is unknown regarding the response of neural structures to rapidly fluctuating electrical fields. The clinical reports to date do not provide sufficient information to properly evaluate the mechanisms that result in successful or unsuccessful treatment. Conclusions KHFAC nerve block has significant potential as a means of controlling nerve activity for the purpose of treating disease. However, early clinical studies in the use of high frequency currents for the treatment of pain have not been designed to elucidate mechanisms or allow direct comparisons to preclinical data. We strongly encourage the careful reporting of the parameters utilized in these clinical studies, as well as the development of outcome measures that could illuminate the mechanisms of this modality.

Electrical stimulation of renal nerves for modulating urine glucose excretion in rats

“…Although nerve conduction block experiments using kilohertz frequency stimulation have been typically performed using cuff electrodes encircling myelinated motor neurons while monitoring muscle tension for block validation (Kilgore and Bhadra 2014;Bhadra and Kilgore 2005), nerve block has also been demonstrated on purely unmyelinated fibers using suction electrodes and confirmed by direct recordings of action potential propagation (Joseph and Butera 2009). In this study, the amplitude of sinusoidal kilohertz frequency stimulation was fixed at 15 V, which is expected to be above the threshold for nerve conduction block at the selected frequencies (Joseph and Butera 2011;Bhadra and Kilgore 2005;Patel and Butera 2015).…”

“…However, to validate the true presence of nerve conduction block or increased neural activity, multiple recording and stimulating electrodes must be placed along the renal nerves. Unfortunately, this was difficult to accomplish in this study due to our limited ability to expose and isolate the renal nerves (2 -4 mm), in addition to the anticipated noise contamination issues between adjacent stimulating and recording electrodes (Kilgore and Bhadra 2014). Additional experiments are required to examine the mechanism of action for stimulation of renal nerves.…”

“…A following study determined that the observed glycosuria and improved glucose tolerance were a result of reduced activity in renal sympathetic nerves (Chhabra et al 2017). A non-pharmaceutical and reversible approach that has emerged in recent years for reducing nerve activity is kilohertz frequency stimulation, which has demonstrated nerve conduction block on multiple types of nerves (Kilgore and Bhadra 2014;Joseph and Butera 2009;Joseph and Butera 2011). We hypothesized that kilohertz frequency stimulation (1-50 kHz) on renal nerves would attain similar results to renal denervation and induce urine glucose excretion.…”

Alternating current and infrared produce an onset-free reversible nerve block

“…ACIR produced complete onset response block in each experiment (N ¼ 3). The onset response, which has previously been shown to be variable over time, 5 was not identical before, during, and after block, but the block of the onset response was always complete.…”

“…5,6 KHFAC is effective in vertebrate myelinated axons, 5 and in unmyelinated axons from the marine mollusk Aplysia. 7 Nerve block obtained with KHFAC is consistently associated with an initial "onset response," during which the nerve fires rapidly for milliseconds to seconds.…”