Injured peripheral nerves maintain the capability to regenerate, but the regenerative process is slow and functional recovery is very poor. A faster nerve-regeneration was found using treadmill training programs and a role of BDNF signalling was proposed in explaining this improvement.

Recently, the muscle expression of BDNF mRNA and protein under activity control has been reported, encouraging us to study the effect of chronic treadmill mid-intensity running on adult rat muscle re-innervation and to explore the involvement of BDNF and Trk receptors. After nerve crush, muscle re-innervation was evaluated using intracellular recordings, tension recordings, immunostaining, and Western-blot analyses. An extensive muscle multiple innervation was found in running rats that was fully reversed to control values blocking Trk receptors or interrupting the running activity. An increase of muscle multiple innervation was also found in sedentary rats treated with a selective TrkB receptor agonist. The expression of TrkB receptors by intramuscular axons was demonstrated and an increased muscle expression of BDNF was found in running animals. The increase of muscle multiple innervation correlated with a faster muscle re-innervation we found in running animals. We conclude that when regenerating axons contact muscle cells, muscle activity progressively increases modulating BDNF and possibly other growth factors that acting via Trk receptors, induce axon sprouting to re-innervate skeletal muscle. An important role for muscle activity programs in functional rehabilitation is suggested.