Conditioning electrical stimulation fails to enhance sympathetic axon regeneration

Peripheral nerve injuries are common, and there is a critical need for the development of novel treatments to complement surgical repair. Conditioning electrical stimulation (CES) is a novel variation of the well-studied perioperative electrical stimulation treatment paradigm. CES is a clinically attractive alternative because of its ability to be performed at the bedside prior to a scheduled nerve repair surgery. Although 60 minutes of CES has been shown to enhance motor and sensory axon regeneration, the effects of CES on sympathetic regeneration are unknown. We investigated how two clinically relevant CES paradigms (10 minutes and 60 minutes) impact sympathetic axon regeneration and distal target reinnervation. Our results indicate that the growth of sympathetic axons is inhibited by CES at acute time points, and at a longer survival time point post-injury, there is no difference between sham CES and the CES groups. We conclude sympathetic axons may retain some regenerative ability, but no enhancement is exhibited after CES, which may be accounted for by the inability of the electrical stimulation paradigm to recruit the small-caliber sympathetic axons into activity. Furthermore, 10-minute CES did not enhance motor and sensory regeneration with a direct repair, and neither 60-minute nor 10-minute CES enhanced motor and sensory regeneration through a graft. Further studies will be needed to optimize electrical stimulation parameters to enhance the regeneration of all neuron types.