The declining capacity for injured peripheral nerves to regenerate their axons 
with time and distance is accounted for, at least in part, by the chronic 
axotomy of the neurons and Schwann cell denervation prior to target 
reinnervation. A largely unrecognized site of delay is the surgical suture site 
where, in rats, 4 weeks is required for all neurons to regenerate their axons 
across the site. Low frequency stimulation for just 1 h after surgery 
accelerates this axon crossing in association with upregulation of neurotrophic 
factors in the neurons. We translated these findings to human patients by 
examining the number of reinnervated motor units in the median nerve-innervated 
thenar muscles before and after carpel tunnel release surgery in a randomized 
controlled trial. Motor unit number estimates (MUNE) in patients with moderate 
and severe carpal tunnel syndrome were significantly lower than normal. This 
number increased significantly by 6-8 months after surgery and reached normal 
values by 12 months in contrast to a non-significant increase in the control 
unstimulated group. Tests including the Purdue Pegboard Test verified the more 
rapid functional recovery after stimulation. The data indicate a feasible 
strategy to promote axonal regeneration in humans that has the potential to 
improve functional outcomes, especially in combination with strategies to 
sustain the regenerative capacity of neurons and the support of Schwann cells 
over distance and time.