Reactive oxygen species contribute to neuropathic pain and locomotor dysfunction via activation of CamKII in remote segments following spinal cord contusion injury in rats

In this study, we examined whether blocking spinal cord injury (SCI)-induced increases in reactive oxygen species (ROS) by a ROS scavenger would attenuate below-level central neuropathic pain and promote recovery of locomotion. Rats with T10 SCI developed mechanical allodynia in both hind paws and overproduction of ROS, as assayed by Dhet intensity, in neurons in the lumbar 4/5 dorsal horn (*P < 0.05). To scavenge ROS, phenyl-N-tert-butylnitrone (PBN, a ROS scavenger) was administered immediately after SCI and for 7 consecutive days (early treatment) by either intrathecal (it; 1 and 3 mg) or systemic (ip; 10, 50 and 100 mg) injections. In addition, the high doses of it (3 mg) or ip (100 mg) injections were performed at 35 days (delayed treatment) after SCI. High doses of PBN (ip, 100 mg, and it, 3 mg) significantly attenuated mechanical allodynia in both hind paws at both early and delayed treatments, respectively (*P < 0.05). The abnormal hyperexcitability of wide dynamic range neurons after SCI was significantly attenuated by both early and delayed PBN treatment (*P < 0.05). Early PBN treatment (100 mg, ip, and 3 mg, it) attenuated overproduction of ROS in neurons in the lumbar 4/5 dorsal horn. In addition, it and ip t-BOOH (ROS donor) treatment dose-dependently produced mechanical allodynia in both hind paws (*P < 0.05). Both SCI and t-BOOH treatment groups showed significantly increased phospho-CamKII (pCamKII) expression in neurons and KN-93 (an inhibitor of pCamKII) significantly attenuated mechanical allodynia (*P < 0.05). In addition, high doses of PBN significantly promoted the recovery of locomotion (*P < 0.05). In conclusion, the present data suggest that overproduction of ROS contribute to sensory and motor abnormalities in remote segments below the lesion after thoracic SCI. Published by Elsevier B.V. on behalf of International Association for the Study of Pain.