Short- but not long-lasting treadmill running reduces allodynia and improves functional recovery after peripheral nerve injury

We analyzed the effects of different treadmill running protocols on the functional recovery after chronic constriction injury (CCI) of the sciatic nerve in mice. We found that a treadmill protocol of short-lasting running (1 h/d for 5 days after CCI) reduced the neuropathy-induced mechanical allodynia and normalized the weight bearing and the sciatic static index of the injured hindpaw. At difference, a treadmill protocol of long-lasting running (1 h/d for more than 5 days after CCI) was unfavorable both for allodynia and for functional recovery. Behavioral results were correlated with immunofluorescence assays of microglia and astrocytes activation in L4/L5 lumbar spinal cord sections. We found a differential pattern of activation characterized by: (i) reduced microglia expression, after both short- and long-lasting treadmill running; (ii) reduced astrocytes expression after short-lasting treadmill running; and, (iii) persistence of astrocytes expression after long-lasting treadmill running. Finally, in sections of injured sciatic nerves, we analyzed the expression of Cdc2 and GAP-43 proteins that are both up-regulated during peripheral regenerative processes. Compared to mice subjected to long-lasting treadmill running, mice subjected to short-lasting treadmill running showed an acceleration of the regenerative processes at the injured sciatic nerve. Our data demonstrate that short-lasting treadmill running, by reducing the neuropathic pain symptoms and facilitating the regenerative processes of the injured nerve, have beneficial rehabilitative effects on the functional recovery after peripheral nerve injury.