Reduction of muscle contraction and pain in electroporation-based treatments: An overview

Table 1 Summary of the studies analysed in this review

		Electroporation protocol
Ref.			Type of pulse	Number of pulses	Pulse duration	Pulse frequency	Electric field	Muscle contraction/pain reduction
Daskalov et al[36], 1999	In vivo	ECT	Monophasic	1 burst of 8 pulses	100 μs	1 Hz	0.33-1.25 kV/cm	Achievable with biphasic pulses
			Biphasic	1 burst of 8 pulses	50-0-50 μs	1 Hz
			Biphasic	1 burst of 8 pulses	50-0-50 μs	Approximately 909 Hz
Miklavcic et al[37], 2005	In vivo	ECT	Monopolar	1 burst of 8 pulses	100 μs	1 to 5000 Hz (ten or five steps)	88 or 313 V/cm	Achievable with high frequency pulses
Zupanic et al[38], 2007	In vivo	ECT	Monopolar	1 burst of 8 pulses	100 μs	1 Hz	600 V/cm	Achievable with high frequency pulses
			Monopolar	1 burst of 8 pulses	100 μs	5000 Hz
Spugnini et al[39], 2014	In vitro	ECT	Biphasic	1 burst of 8 pulses	50-10-50 μs	9 kHz	1.3 kV/cm	Achievable with biphasic pulses
	In vivo
Scuderi et al[40], 2019	In vitro	ECT	Monopolar	1 burst of 8 pulses	100 μs	1 Hz	1.2 kV/cm	Achievable with bipolar HF-EP
			Bipolar	8 bursts of 50 pulses	1-1-1 μs	250 kHz	3 kV/cm
García-Sánchez et al[41], 2020	In vivo	ECT	Unipolar	Bursts of 8 pulses	100 μs	1 Hz	1.3 kV/cm	Achievable with sinusoidal pulses
			Bipolar	Number of bursts and pulses depend on experiments and frequency	100 μs-5 ms	10-100 kHz	> 1.3 kV/cm
			Sinusoidal
Golberg and Rubinsky[28], 2012	Numerical	-	Monopolar	1 pulse	100 μs	-	> 800 V/cm	Achievable with an appropriate electrode design and arrangement
Arena et al[32], 2011	In vivo	IRE	Monopolar	90-180 pulses	200 μs	1 Hz	0.5-2 kV/cm	Achievable with H-FIRE
			Bipolar	180 bursts of 50 pulses	2-0-2 μs	250 kHz	1-4 kV/cm
			Bipolar	180 bursts of 100 pulses	1-0-1 μs	500 kHz	4 kV/cm
Sano et al[42], 2014	In vitro	IRE	Bipolar	80 bursts of 1 pulse	50-2-50 μs	1 Hz	1.5 kV/cm	Achievable with biphasic pulses
Sano et al[43], 2015	In vitro	IRE	Monopolar	1 pulse	100 μs	1 Hz	1.5 kV/cm	Achievable with bipolar pulses
	In vivo		Bipolar	8-120 bursts of 1-200 pulses	Pulse width: 250 ns-50 μs	20 to 20000 kHz (seven steps)	Approximately 0.5-2 kV/cm
Sweeney et al[33], 2016	In vitro	IRE	Monopolar	1 burst of 200 pulses	100 μs	2 kHz	750-1250 V/cm	Achievable with high-frequency bipolar pulses
			Bipolar	200 bursts of 50 pulses	1 -1-1 μs	250 kHz	1250 V/cm
			Bipolar	200 bursts of 50 pulses	1-4-1 μs	100 kHz	1250 V/cm
Yao et al[44], 2017	In vivo	IRE	Bipolar	90 bursts of 50 pulses	2-2-2 μs	250 kHz	1-2 kV/cm	Achievable with H-FIRE and insulated needle electrodes
			Bipolar	90 bursts of 20 pulses	5-2-5 μs	Approximately 143 kHz
			Bipolar	90 bursts of 10 pulses	10-2-10 μs	Approximately 83 kHz
			Bipolar	90 bursts of 4 pulses	25-2-25 μs	Approximately 37 kHz	1–1.75 kV/cm
			Bipolar	90 bursts of 2 pulses	50-2-50 μs	Approximately 20 kHz	1–1.5 kV/cm
			Monopolar	90 bursts of 1 pulse	100 μs	1 Hz	0.8–1.5 kV/cm
Sano et al[29], 2018	Ex vivo	IRE	Monopolar	5 pulses	100 μs	1 Hz	1 kV/cm	Achievable with (symmetric) H-FIRE pulses
			Bipolar	5 bursts of 1-200 pulses	2-2-2 μs	Not available	0.17-1.7 kV/cm

ECT: Electrochemotherapy; H-FIRE: High-frequency irreversible electroporation; HF-EP: High frequency electroporation; IRE: Irreversible electroporation.