The frequent poor functional outcomes after delayed surgical repair of injured human peripheral nerves results in progressive downregulation of growth-associated genes in parallel with reduced neuronal regenerative capacity under each of the experimental conditions of chronic axotomy of neurones that remain without target contact, chronic distal nerve stump denervation, and chronic muscle denervation. Brief (1 h) low-frequency (20 Hz) electrical stimulation (ES) accelerates the outgrowth of regenerating axons across the surgical site of microsurgical repair of a transected nerve. Exercise programmes also promote nerve regeneration with the combination of ES and exercise being the most effective. An ES conditioning lesion of intact nerve (CES) accelerates both axonal outgrowth and regeneration rate after the surgical repair of a more distal injury to the nerve, in contrast to ES of a repaired injury nerve that accelerates only the axon outgrowth. A CES accelerates both axonal outgrowth and regeneration rate after the surgical repair of a more distal injury to the nerve, in contrast to ES of a repaired injury nerve that accelerates only the axon outgrowth. The loss of contractility of permanently denervated muscles in cauda equinae-injured patients with accompanying severe loss of muscle mass, disarray of thick and thin contractile filaments, and disorganization of the sarcoplasmic reticulum that controls calcium delivery to the filaments, is alleviated by a 2-year programme of daily ES of the quadriceps muscle. These findings hold promise for recovery and rehabilitation in patients who suffer injury to the neuromuscular system. KEY POINTS: Poor functional outcomes after delayed surgical repair of injured human peripheral nerves are replicated by chronic neuronal axotomy, Schwann cell denervation in a nerve autograft, and muscle denervation. Exponential decline in expression of growth-associated genes accompanies the same decline in regenerative capacity. Brief (1 h) low-frequency (20 Hz) electrical stimulation (ES) that generates action potential conduction to the neuronal soma accelerates the outgrowth of regenerating axons across the surgical repair site of the transected nerve, even after delayed surgery. The same ES regimen accelerates muscle reinnervation in patients with chronic nerve injury who undergo carpal tunnel syndrome release surgery. A 2-year programme of daily ES of permanently denervated quadriceps muscles in cauda equinae-injured patients reinstated their contractility and organization.
© 2024 The Author(s). The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.