Following nerve injury and regeneration, a transient phase of multiple innervation of muscle cells occurs. Successively, 1:1 ratio of innervation is progressively reached. Two mechanisms has been proposed to explain these processes: nerve-terminal competition for muscle released growth factors and the different pattern of axon activity. We showed running to enhance muscle expression of BDNF, a trophic factor inducing sprouting. Thus we investigated the role of running early in post-traumatic reinnervation.

We used intracellular recordings and miography to evaluate the reinnervation of soleus muscle following nerve crush, in running and sedentary rats.

In sedentary rats, about 10% of recorded muscle cells was found to be multiply innervated from 7 to 45 days from nerve crush. In runners, multiple innervation reached 34% 10 days after nerve crush and this percentage gradually decreased during the following days, although it remained significantly higher with respect to sedentary group. This effect of running was reversible.

Both in runner and sedentary rats all axons were showed to be regenerated 10 days after nerve crush, but in runners recovery of muscle strength was higher and muscle reinnervation was almost complete.

On the basis of present results, we hypothesize that intense motoneuron-muscle activity might induce up-regulation of one or more neurotrophic factors released by muscle cells, that might induce motor nerve terminal sprouting and consequent massive muscle cell multiple innervation. This model allow to link nerve-terminal competition and axon activity hypotheses and is intriguing considering the importance of physical activity during rehabilitation and the correlated exercise protocol planning.