千频交流电刺激在外周神经传导阻断中的作用

感觉、运动或自主神经系统的异常病理活动与疼痛和痉挛等多种神经机能障碍有关。千频交流电（kilohertz frequency alternating current,KHFAC）刺激是一种阻断异常病理活动在外周神经内传导的有效方法,它在缓解相关神经机能障碍方面具有临床应用潜力。KHFAC产生的神经传导阻断受千频信号波形和参数、阻断电极设置和位置以及神经纤维类型和直径等因素影响,具有快速性、可控性、可逆性、局部作用和副作用小的特点。但是,在产生完全传导阻断前,KHFAC首先在靶向神经上激活一簇高频初始放电,这种初始响应可能导致肌肉抽搐或疼痛感。同时,在撤去KHFAC后处于阻断状态的靶向神经需要经历一段时间才能恢复正常传导能力,这是该技术导致的后续效应。目前,关于KHFAC阻断神经传导的生物物理机制假说包括千频信号诱发K⁺通道激活和Na⁺通道失活。本文首先介绍了KHFAC技术的电生理实验研究方法和计算模型仿真方法,然后综述目前关于KHFAC作用下神经传导阻断的研究进展,重点论述初始响应特性及消除方法、传导阻断的后续效应、刺激波形和参数的影响、电极设置与位置的影响以及该技术潜在的临床应用,同时归纳KHFAC阻断神经传导的生物物理机制,最后对该技术未来的相关研究进行展望。

Effects of Kilohertz Frequency Alternating Current Stimulation on Peripheral Nerve Conduction Block

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.