Effects of Kilohertz Frequency Alternating Current Stimulation on Peripheral Nerve Conduction Block
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School of Electrical and Information Engineering, Tianjin University, Tianjin 300072, China

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This work was supported by grants from The National Natural Science Foundation of China (61771330, 62071324, 62171312) and Tianjin Municipal Natural Science Foundation (19JCQNJC01200,19JCZDJC36500).

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    Abstract:

    Undesirable pathological activities in sensory, motor or autonomic nerve are related to multiple neurological disorders, such as pain and spasticity. Kilohertz frequency alternating current (KHFAC) stimulation is an effective method for blocking the conduction of undesirable pathological activities in peripheral nerves, which has potentials for alleviating neurological disease symptoms in clinics. The nerve conduction block caused by KHFAC is influenced by kilohertz signal waveform and parameters, blocking electrode design and position as well as nerve fiber type and diameter, which is rapid, controllable, reversible, locally acting, and has less side effect. However, the target nerve is first activated to generate a burst of high-frequency firing by KHFAC before entering a state of complete conduction block. Such onset firing is likely to result in muscle contraction or painful sensation, which limits the clinical applications of KHFAC nerve block. Meanwhile, the conduction ability of target nerves usually requires a period of time to recover after the cessation of KHFAC, which is the carry-over effect produced by this technology. Since KHFAC stimulation has important potential applications in nerve conduction block, it is necessary to systematically review the developments of preclinical studies of this technology. In this paper, we first introduce the methods used in electrophysiological experiments and computational modeling simulations of KHFAC stimulation. Then, we present an exhaustive review on the main findings of KHFAC nerve block. For onset response, we describe its temporal characteristics and also review the existing methods proposed to reduce or eliminate such undesirable firing. For carry-over effect, we summarize the duration of poststimulation block in different target nerves and also review the underlying ionic mechanisms. For the effects of stimulus waveform and parameters, we focus on the minimal block frequency, block threshold, and KHFAC waveform. For the effects of blocking electrode and position, we focus on the electrode type, surface area, contact separation distance as well as electrode-fiber distance. For potential clinical applications, we summarize earlier explorations including the KHFAC block of vagus, sensory, motor, pudendal, and autonomic nerves in human trails. For the mechanisms of KHFAC nerve block, we introduce two biophysical explanations, which are K+ channel activation and Na+ channel inactivation caused by kilohertz signals. Finally, we raise several key issues on KHFAC stimulation of peripheral nerves that need to be addressed in the future. We highly suggest further determination of the effective stimulus parameters, nerve responses, and underlying mechanisms involved in different species for successful translation of KHFAC block, especially in human beings.

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YI Guo-Sheng, ZHAO Qiang, BAI Rui-Feng, WEI Xi-Le, WANG Jiang. Effects of Kilohertz Frequency Alternating Current Stimulation on Peripheral Nerve Conduction Block[J]. Progress in Biochemistry and Biophysics,2022,49(8):1482-1497

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History
  • Received:September 26,2021
  • Revised:November 29,2021
  • Accepted:November 30,2021
  • Online: August 19,2022
  • Published: August 20,2022