Systematic Reviews
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. May 24, 2021; 12(5): 367-381
Published online May 24, 2021. doi: 10.5306/wjco.v12.i5.367
Reduction of muscle contraction and pain in electroporation-based treatments: An overview
Roberta Fusco, Elio Di Bernardo, Valeria D'Alessio, Simona Salati, Matteo Cadossi
Roberta Fusco, Elio Di Bernardo, Valeria D'Alessio, Simona Salati, Matteo Cadossi, Department of Medical Oncology, IGEA SpA, Carpi 41012, Modena, Italy
Author contributions: Fusco R, Di Bernardo E, D'Alessio V wrote the manuscript; Salati S and Cadossi M revised the manuscript.
Conflict-of-interest statement: The authors declare that they have no competing interests.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Valeria D'Alessio, Department of Medical Oncology, IGEA SpA, Via Parmenide 10A, Carpi 41012, Modena, Italy.
Received: December 23, 2020
Peer-review started: December 24, 2020
First decision: March 17, 2021
Revised: March 17, 2021
Accepted: April 22, 2021
Article in press: April 22, 2021
Published online: May 24, 2021

In the first studies of electrochemotherapy (ECT), small cutaneous metastases were treated and only mild or moderate pain was observed; therefore, pain was not considered a significant issue. As the procedure began to be applied to larger cutaneous metastases, pain was reported more frequently. For that reason, reduction of both muscle contractions and pain have been investigated over the years.


To present an overview of different protocols described in literature that aim to reduce muscle contractions and pain caused by the electroporation (EP) effect in both ECT and irreversible EP treatments.


Thirty-three studies published between January 1999 and November 2020 were included. Different protocol designs and electrode geometries that reduce patient pain and the number of muscle contractions and their intensity were analysed.


The analysis showed that both high frequency and bipolar/biphasic pulses can be used to reduce pain and muscle contractions in patients who undergo EP treatments. Moreover, adequate electrode design can decrease EP-related morbidity. Particularly, needle length, diameter and configuration of the distance between the needles can be optimised so that the muscle volume crossed by the current is reduced as much as possible. Bipolar/biphasic pulses with an inadequate pulse length seem to have a less evident effect on the membrane permeability compared with the standard pulse protocol. For that reason, the number of pulses and the voltage amplitude, as well as the pulse duration and frequency, must be chosen so that the dose of delivered energy guarantees EP efficacy.


Pain reduction in EP-based treatments can be achieved by appropriately defining the protocol parameters and electrode design. Most results can be achieved with high frequency and/or bipolar/biphasic pulses. However, the efficacy of these alternative protocols remains a crucial point to be assessed further.

Keywords: Electrochemotherapy, Irreversible electroporation, Pain, Muscle contraction, Monopolar or monophasic pulses, Bipolar or biphasic pulses

Core Tip: This is an overview of different published protocols that aim to reduce muscle contractions and pain due to the electroporation (EP) effect. The analysis showed that both high frequency and bipolar/biphasic pulses can be used to reduce pain and muscle contractions. Moreover, appropriate electrode design can lower EP-related morbidity.