Electrical stimulation to enhance peripheral nerve regeneration: Update in molecular investigations and clinical translation

Peripheral nerve injuries are common and frequently result in incomplete functional recovery even with optimal surgical treatment. Permanent motor and sensory deficits are associated with significant patient morbidity and socioeconomic burden. Despite substantial research efforts to enhance peripheral nerve regeneration, few effective and clinically feasible treatment options have been found. One promising strategy is the use of low frequency electrical stimulation delivered perioperatively to an injured nerve at the time of surgical repair. Possibly through its effect of increasing intraneuronal cyclic AMP, perioperative electrical stimulation accelerates axon outgrowth, remyelination of regenerating axons, and reinnervation of end organs, even with delayed surgical intervention. Building on decades of experimental evidence in animal models, several recent, prospective, randomized clinical trials have affirmed electrical stimulation as a clinically translatable technique to enhance functional recovery in patients with peripheral nerve injuries requiring surgical treatment. This paper provides an updated review of the cellular physiology of electrical stimulation and its effects on axon regeneration, Level I evidence from recent prospective randomized clinical trials of electrical stimulation, and ongoing and future directions of research into electrical stimulation as a clinically feasible adjunct to surgical intervention in the treatment of patients with peripheral nerve injuries.