The use of brief post-surgical low frequency electrical stimulation to enhance nerve regeneration in clinical practice

Abstract

Despite efforts to enhance peripheral nerve regeneration, there has been little progress in improving clinical outcomes. Recently, a method of brief post-surgical low frequency electrical stimulation of surgically repaired nerves has been developed. It was shown to accelerate axon outgrowth across the repair site and it hastened target reinnervation. In this brief review, we describe the mechanistic insights and functional impacts of the post-surgical electrical stimulation that have been gained through animal studies. Brain-derived neurotrophic factor, cyclic AMP and regeneration-associated genes play a vital role in expediting the outgrowth of axons across the injury site. The method of stimulation has also been shown to be effective in patients with severe compressive neuropathy as well as those with digital nerve laceration. Its clinical feasibility and positive impact open the door of further clinical translation in other peripheral nerve injuries.

© 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Figures

Figure 1. Effects of electrical stimulation on nerve regeneration in animal models and humans

A, in a rat femoral nerve injury model, the nerve was cut above the bifurcation. Electrical stimulation at 20 Hz was applied to the proximal nerve stump for an hour immediately after suture repair. The neurons were allowed to regenerate their axons for up to 8 weeks before retrogradely transported dyes were applied to the distal stump 25 mm from the repair site. B, all retrogradely labelled motoneurons that regenerated their axons were counted in the spinal cord. Animals that received electrical stimulation showed accelerated growth taking only 3 weeks as opposed to 8 weeks for sham‐stimulated neurons in control rats. The dashed line represents mean motoneuron number in control animals. C, in a double‐blind randomized controlled trial, the same electrical stimulation treatment was applied to patients with marked median motor axon loss due to severe compression in the carpal tunnel. The extent of reinnervation was evaluated using motor unit number estimation. D, similar to the animal study data, significantly greater motor reinnervation was found in the treatment group compared with those who received sham stimulation. As in panel B, the dashed line represents mean motoneuron number in control animals. Because of the difference in size, the actual time frame of follow‐up (1 year) had to be much longer than in the rats. E, the impact of brief low frequency electrical stimulation is represented schematically. The effect of the electrical stimulation is to accelerate axon outgrowth across the repair site with the result that muscle reinnervation occurs more rapidly.