Prolonged analgesia by spinal cord stimulation following a spinal injury associated with activation of adult neural progenitors.

OBJECTIVES Responses of spinal progenitors to SCS following SCI in rats were assessed to reveal their potential contribution to SCS-induced analgesia. MATERIALS AND METHODS Rats were implanted with spinal epidural electrodes at T12 rostral to a quadrant dorsal horn injury at T13. Further groups additionally received either micro-lesion to the dorsolateral funiculus (DLF) or gabapentin (10mg/kg). SCS was performed at 25Hz for 10min on day 4 (early-SCS) and at 10Hz for 10min on day 8 (late-SCS) after injury. Paw withdrawal threshold (PWT) was measured before injury, 30min before or after SCS, and before cull on day 14, followed by immunostaining assessment. RESULTS PWT in uninjured animals (51.0±4.0g) was markedly reduced after SCI (17.3±2.2g). This was significantly increased by early-SCS (38.5±5.2g, p<0.01) and further enhanced by late-SCS (50.9±1.9g, p<0.01) over 6 days. Numbers of neural progenitors expressing nestin, Sox2, and doublecortin (DCX) in the spinal dorsal horn were increased 6 days after SCS by 6-fold, 2-fold and 2.5-fold, respectively (p<0.05-0.01). The elevated PWT evoked by SCS was abolished by DLF micro-lesion (48.9±2.6g vs. 19.0±3.9g, p<0.01) and the number of nestin+ cells was reduced to the level without SCS (p<0.05). Gabapentin enhanced late-SCS-induced analgesia from 37.0±3.9g to 54.0±0.8g (p<0.01) and increased GABA-ergic neuronal marker vGAT-positive newborn cells 2-fold (p<0.01). CONCLUSIONS Spinal progenitor cells appears to be activated by SCS via descending pathways, which may be enhanced by gabapentin and potentially contributes to relief of SCI-induced neuropathic pain.