Changes in Na+ channel expression and nodal persistent Na+ currents associated with peripheral nerve regeneration in mice

Patients with peripheral neuropathy frequently suffer from positive sensory (pain and paresthesias) and motor (muscle cramping) symptoms even in the recovery phase of the disease. To investigate the pathophysiology of increased axonal excitability in peripheral nerve regeneration, we assessed the temporal and spatial expression of voltage-gated Na+ channels as well as nodal persistent Na+ currents in a mouse model of Wallerian degeneration. Crushed sciatic nerves of 8-week-old C57/BL6J male mice underwent complete Wallerian degeneration at 1 week. Two weeks after crush, there was a prominent increase in the number of Na+ channel clusters per unit area, and binary or broad Na+ channel clusters were frequently found. Excess Na+ channel clusters were retained up to 20 weeks post-injury. Excitability testing using latent addition suggested that nodal persistent Na+ currents markedly increased beginning at week 3, and remained through week 10. These results suggest that axonal regeneration is associated with persistently increased axonal excitability resulting from increases in the number and conductance of Na+ channels.