High‐ and low‐frequency transcutaneous electrical nerve stimulation delay sciatic nerve regeneration after crush lesion in the mouse

Abstract

The stimulation of peripheral nerve regeneration has been studied in different ways, including the use of electrical fields. The capacity of this modality to enhance nerve regeneration is influenced by the parameters used, including current type, frequency, intensity, and means of administration. Transcutaneous electrical nerve stimulation (TENS) is a frequently used form of administering electrical current to the body, but its effects on peripheral nerve regeneration are not known. This study assessed the influence of TENS on sciatic nerve regeneration, using a model of crush lesion in the mouse. Mice were stimulated 30 min a day, 5 days a week, for 5 weeks with both high- (100 Hz) and low- (4 Hz) frequency TENS. Control animals had the sciatic nerve crushed but were not stimulated. Assessment was performed weekly by functional analysis using the Static Sciatic Index for the mouse and at the end of the experiment by light and electron microscopy. The results showed that although there were no differences between the groups regarding the Static Sciatic Index values, TENS led to nerves with morphological signs of impaired regeneration. At light microscopy level, TENS nerves presented more axons with dark axoplasm, signs of edema, and a less organized cytoarchitecture. Electronmicrographs showed fewer and thinner thick myelinated fibers and increased number of Schwann cell nuclei. Myelinated axon diameters and density and diameter of nonmyelinated fibers were not affected by TENS, leading to the conclusion that this regimen of electrical stimulation leads to a delayed regeneration after a crush lesion of the sciatic nerve in the mouse. All these effects were more pronounced on high-frequency TENS nerves.

Effects of electrical stimulation and stretching on the adaptation of denervated skeletal muscle: implications for physical therapy

“…Recently, it was demonstrated that the use of ES in the initial phase after nerve crush injury in rats was harmful, leading to a delay of functional recovery, muscle hipoexcitability and severe muscle atrophy 43 . Another study that applied ES directly on the crushed nerve of mice also showed signs of delay in the nerve regeneration process, such as edema, reduced organization of axonal cytoarchitecture and fewer number of myelin fibers 44 . Finally, studies in humans that have used ES on muscle with chronic denervation also showed no protective effect on muscle mass and no functional recovery 45 .…”

The sciatic nerve injury model in pre-clinical research

“…Yet, high reproducibility of the lesion makes this experimental model also particularly suitable for investigating regeneration-related time course changes (De Leon et al, 1991;Gupta and Channual, 2006;Sta et al, 2014). Finally, changes in the outcome of nerve regeneration after a crush injury of the sciatic nerve might be used as a pre-clinical end-point predictor of the effectiveness of a therapeutic agent and/or tissue engineering strategy on nerve regeneration (Fleming et al, 2007;Amado et al, 2008;Baptista et al, 2008;Gigo-Benato et al, 2010;Dadon-Nachum et al, 2011;Kilic et al, 2013;Wang et al, 2014).…”

Effects of Pulsed Electromagnetic Fields on Peripheral Nerve Regeneration Using Allografts in Sciatic Nerve: An Animal Model Study

“…Exposure to PEMF as a pretreatment prior to crush injury has resulted in acceleration of axonal regrowth, and consistent with the stimulation of regenerative neurite outgrowth increased functional outcomes such as walking behavior [6][7][8][9]. PEMF has also been shown to promote neurite outgrowth in vitro [7]. Others have demonstrated that prolonged PEMF regimen had led to delayed histological peripheral nerve regeneration and increased oxidative stress but no loss of function recovery [10].…”

“…Pulsed electromagnetic fields treatment was performed based on a method described by others [6][7][8][9]. In brief, on days 1-5, each animal was placed in an all-plastic restrainer located between Helmholtz coils and treated for 4 h each day with the PEMF signal generator either activated (PEMFgroup) or not activated (Normal group).…”