Grant: Project Grant

Peripheral nerve injury is common, especially among young, working individuals. Unfortunately, with current treatments, nerve regeneration following severe injury is often poor. A major reason is the very slow rate of regrowth, at 0.5-1 mm/day. Through animal studies, there is strong evidence that a conditioning lesion (CL), in which a nerve is deliberately damaged before the actual nerve injury, increases the speed of axon regeneration up to 3 mm/day. Faster regeneration increases the likelihood of functional motor and sensory recovery, therefore this accelerated nerve regeneration is extremely important. CL, however, cannot be applied to patients because it is not ethically acceptable or clinically feasible to subject patients to an additional surgery to crush a nerve. As such, another method of conditioning that does not require injuring the nerve is needed. A recent study showed brief electrical stimulation (ES) administered prior to injury increased the speed of regeneration of sensory neurons grown in culture. This opens the possibility that conditioning ES may be an clinically feasible alternative to CL. This treatment would be particularly applicable to nerve transfer surgeries in which a healthy nerve is cut and rerouted to a damaged nerve in order to reinnervate a muscle. These increasingly common elective procedures are pre-planned so they are ideally suited for conditioning ES. Our goal is to systemically evaluate the effects and mechanisms of conditioning ES on nerve regeneration and functional recovery in a rat model. We will concurrently perform a pilot clinical trial to ensure a seamless bidirectional translation between the bench and the bedside.