Brief Transvertebral Electrical Stimulation of the Spinal Cord Improves the Specificity of Femoral Nerve Reinnervation

Abstract

Background. Functional outcomes are generally poor following peripheral nerve injury (PNI). The reason is multifactorial but includes the misdirection of regenerating axons to inappropriate end organs. It has been shown that brief electrical stimulation (Estim) of nerves has the potential to improve the accuracy and rate of peripheral axon regeneration. Objective. The present study explores a novel percutaneous transvertebral approach to Estim, which was tested in the mouse femoral nerve model. Methods. Inspired by the protocol of Gordon and colleagues (ie, 20 Hz, for 1 hour), we applied Estim to the cervicothoracic spinal cord (SC-Estim) to remotely activate lumbar motor neurons following transection and repair of the femoral nerve. Fluorescent dyes were applied to the distal nerve to label reinnervating cells. Sections of nerve were taken to quantify the numbers of reinnervating axons as well as to stain for a known femoral axon guidance molecule—polysialylated neural cell adhesion molecule (PSA-NCAM). Results. In comparison to sham treatment, SC-Estim led to significantly greater expression of PSA-NCAM as well as improved the specificity of motor reinnervation. Interestingly, although SC-Estim did not alter the number of early reinnervating (ie, pioneer) axons, there was a reduction in the number of retrogradely labeled neurons at 2 weeks postrepair. However, by 6 weeks postrepair, there was no difference in the number of neurons that had reinnervated the femoral nerve. Conclusions. The present findings support the development of SC-Estim as a novel approach to enhance the specificity of reinnervation and potentially improve functional outcomes following PNI.