Objective: 

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 have been proposed to explain these processes: nerve-terminal competition for muscle released growth factors and the different pattern of axon activity. We previously 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.

Methods: 

We used intracellular recordings (n= 67) and miography (n= 14) to evaluate soleus muscle reinnervation following nerve crush, in runner (n= 22) and sedentary rats (n= 29).

Results: 

In sedentary rats, about 10% of recorded muscle cells were found to be multiply innervated from 7 to 45 days from nerve crush. In runners, multiple innervations 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 (Fig. 1). This effect of running was reversible (n= 5) and disappears blocking trk receptors (n= 11) (Fig. 2). 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.

Conclusions: 

We hypothesize that intense motoneuron-muscle activity might induce up-regulation of one or more neurotrophic factors muscle-released that, via trk receptors, causes an increase of nerve terminal sprouting and massive muscle cell multiple innervation. This model allows to unify nerve terminal competition and axon activity hypotheses of muscle reinnervation mechanism and sheds light on exercise protocol planning during rehabilitation.