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Superoxide produced from mitochondrial oxidative phosphorylation is considered the major source of ROS in neurons during excitation where mitochondrial superoxide levels are normally controlled by superoxide dismutase (SOD-2). The present study hypothesizes that capsaicin-induced secondary hyperalgesia is a consequence of superoxide build-up in spinal dorsal horn neurons and SOD-2 is a major determinant. To test this hypothesis, the spinal levels of SOD-2 activity, inactivated SOD-2 proteins, and mitochondrial superoxide were measured and correlated to the levels of capsaicin-induced secondary hyperalgesia in mice with and without SOD-2 manipulations. The data suggest that superoxide accumulation is a culprit in the abnormal sensory processing in the spinal cord in capsaicin-induced secondary hyperalgesia. Our studies also support the notion that SOD-2 nitration is a critical mechanism that maintains elevated superoxide levels in the spinal cord after capsaicin treatment. Finally, our findings suggest a therapeutic potential for the manipulation of spinal SOD-2 activity in pain conditions.<\/jats:p>","DOI":"10.1523\/jneurosci.3792-08.2009","type":"journal-article","created":{"date-parts":[[2009,1,7]],"date-time":"2009-01-07T17:28:14Z","timestamp":1231349294000},"page":"159-168","source":"Crossref","is-referenced-by-count":138,"title":["Persistent Pain Is Dependent on Spinal Mitochondrial Antioxidant Levels"],"prefix":"10.1523","volume":"29","author":[{"given":"Erica S.","family":"Schwartz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee 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