Electroporation, a technique that uses electrical pulses to temporarily or permanently destabilize cell membranes, is increasingly used in cancer treatment, gene therapy, and cardiac tissue ablation. Although the technique is efficient, patients report discomfort and pain. Current strategies that aim to minimize pain and muscle contraction rely on the use of pharmacological agents. Nevertheless, technical improvements might be a valuable tool to minimize adverse events, which occur during the application of standard electroporation protocols. One recent technological strategy involves the use of high pulse repetition rate. The emerging technique, also referred as “high frequency” electroporation, employs short (micro to nanosecond) mono or bipolar pulses at repetition rate ranging from a few kHz to a few MHz. This review provides an overview of the historical background of electric field use and its development in therapies over time. With the aim to understand the rationale for novel electroporation protocols development, we briefly describe the physiological background of neuromuscular stimulation and pain caused by exposure to pulsed electric fields. Then, we summarize the current knowledge on electroporation protocols based on high pulse repetition rates. The advantages and limitations of these protocols are described from the perspective of their therapeutic application.

电穿孔是一种利用电脉冲暂时或永久破坏细胞膜稳定性的技术，越来越多地用于癌症治疗、基因治疗和心脏组织消融。尽管该技术很有效，但患者报告有不适和疼痛。当前旨在最大程度地减少疼痛和肌肉收缩的策略依赖于药物的使用。尽管如此，技术改进可能是减少应用标准电穿孔方案期间发生的不良事件的宝贵工具。最近的一项技术策略涉及使用高脉冲重复率。这项新兴技术也称为“高频”电穿孔，采用短（微至纳秒）单极或双极脉冲，重复率范围为几 kHz 至几 MHz。这篇综述概述了电场使用的历史背景及其随着时间的推移在治疗中的发展。为了了解新型电穿孔方案开发的基本原理，我们简要描述了神经肌肉刺激和暴露于脉冲电场引起的疼痛的生理背景。然后，我们总结了基于高脉冲重复率的电穿孔方案的当前知识。从治疗应用的角度描述了这些方案的优点和局限性。