Electrical Stimulation to Enhance Axon Regeneration After Peripheral Nerve Injuries in Animal Models and Humans

Abstract

Injured peripheral nerves regenerate their lost axons but functional recovery in humans is frequently disappointing. This is so particularly when injuries require regeneration over long distances and/or over long time periods. Fat replacement of chronically denervated muscles, a commonly accepted explanation, does not account for poor functional recovery. Rather, the basis for the poor nerve regeneration is the transient expression of growth-associated genes that accounts for declining regenerative capacity of neurons and the regenerative support of Schwann cells over time. Brief low-frequency electrical stimulation accelerates motor and sensory axon outgrowth across injury sites that, even after delayed surgical repair of injured nerves in animal models and patients, enhances nerve regeneration and target reinnervation. The stimulation elevates neuronal cyclic adenosine monophosphate and, in turn, the expression of neurotrophic factors and other growth-associated genes, including cytoskeletal proteins. Electrical stimulation of denervated muscles immediately after nerve transection and surgical repair also accelerates muscle reinnervation but, at this time, how the daily requirement of long-duration electrical pulses can be delivered to muscles remains a practical issue prior to translation to patients. Finally, the technique of inserting autologous nerve grafts that bridge between a donor nerve and an adjacent recipient denervated nerve stump significantly improves nerve regeneration after delayed nerve repair, the donor nerves sustaining the capacity of the denervated Schwann cells to support nerve regeneration. These reviewed methods to promote nerve regeneration and, in turn, to enhance functional recovery after nerve injury and surgical repair are sufficiently promising for early translation to the clinic.

Effects of transcutaneous electrical nerve stimulation on chemotherapy-induced peripheral neuropathy symptoms (CIPN): a preliminary case-control study

“…It has been hypothesized that these results relate to the effect of TENS in the modulation of Ca2 + levels and of injured neurons through voltage-dependent channels after nerve injury, factors that would contribute to a decrease in the frequency of the firing of these neurons and stimulate production of neurotrophic factors (BDNF, NGF, and VEGF) and other transcription factors17 ) . In our study, we use modulating frequencies ranging between 7 and 65 Hz.…”

Peripheral nerve injury and myelination: Potential therapeutic strategies

“…Electrical stimulation (ES) represents a promising non‐pharmacological approach to accelerate and promote recovery following peripheral nerve injury (Al‐Majed, Neumann, Brushart, & Gordon, ; Haastert‐Talini et al, ; MacEwan et al 2019; Mendez et al, ; Nix & Hopf, ; Pockett & Gavin, ). Studies in animals and humans have shown that ES promotes preferential reinnervation of both motor and sensory neurons, allowing for a faster recovery (Al‐Majed, Neumann, et al, ; Brushart, Jari, Verge, Rohde, & Gordon, ; Gordon, ). In addition to promoting reinnervation, ES also aids in the remyelination process following peripheral nerve injury (Huang et al, ).…”

A Simple Electrical Stimulation Cell Culture System on the Myelination of Dorsal Root Ganglia and Schwann Cells

“…Electrical stimulation is given to patients with median nerve injury caused by human carpal tunnel syndrome. It has been confirmed that short-term, low-frequency electrical stimulation can significantly promote nerve regeneration and stimulate the feeling of innervation and motor function [6,7], however the specific mechanism is not clear. Therefore, the establishment of an in vitro dorsal root ganglion (DRG)–Schwann cell (SC)–electric stimulation model provides a basis for further study of the mechanism of electrical stimulation of peripheral nerve myelination.…”