Conditioning electrical stimulation promotes functional nerve regeneration

Abstract Peripheral nerve regeneration following injury is often incomplete, resulting in significant personal and socioeconomic costs. Although a conditioning crush lesion prior to surgical nerve transection and repair greatly promotes nerve regeneration and functional recovery, feasibility and ethical considerations have hindered its clinical applicability. In a recent proof of principle study, we demonstrated that conditioning electrical stimulation (CES) had effects on early nerve regeneration, similar to that seen in conditioning crush lesions (CCL). To convincingly determine its clinical utility, establishing the effects of CES on target reinnervation and functional outcomes is of utmost importance. In this study, we found that CES improved nerve regeneration and reinnervation well beyond that of CCL. Specifically, compared to CCL, CES resulted in greater intraepidermal skin and NMJ reinnervation, and greater physiological and functional recovery including mechanosensation, compound muscle action potential on nerve conduction studies, normalization of gait pattern, and motor performance on the horizontal ladder test. These findings have direct clinical relevance as CES could be delivered at the bedside before scheduled nerve surgery.