A nonphysiological repair of the lesioned nerve leading to the formation of neurinomas, altered nerve
conduction, and spontaneous firing is considered the main cause of the events underlying neuropathic
pain. It was investigated whether neural stem cell (NSCs) administration could lead to a physiological
nerve repair, thus to a reduction of neuropathic pain symptoms such as hyperalgesia and allodynia in
a well-established model of this pain (sciatic nerve chronic constriction injury [CCI]). Moreover, since
we and others showed that the peripheral nerve lesion starts a cascade of neuroinflammation-related
events that may maintain and worsen the original lesion, the effect of NSCs on sciatic nerve pro- and antiinflammatory cytokines in CCI mice was investigated. NSCs injected intravenously, when the pathology
was already established, induced a significant reduction in allodynia and hyperalgesia already 3 days
after administration, demonstrating a therapeutic effect that lasted for at least 28 days. Responses changed with the number of administered NSCs, and the effect on hyperalgesia could be boosted by a new NSC
administration. Treatment significantly decreased proinflammatory, activated antiinflammatory cytokines in the sciatic nerve, and reduced spinal cord Fos expression in laminae I-VI. Moreover, in NSC-treated animals, a reparative process and an improvement of nerve morphology is present at a later time.
Since NSC effect on pain symptoms preceded nerve repair and was maintained after cells had disappeared
from the lesion site, we suggest that regenerative, behavioral, and immune NSC effects are largely due to microenvironmental changes they might induce at the lesion site