Persistent Pain Is Dependent on Spinal Mitochondrial Antioxidant Levels

• Published in: The Journal of neuroscience 2009-01, Vol.29 (1), p.159-168
• Main Authors: Schwartz, Erica S, Kim, Hee Young, Wang, Jigong, Lee, Inhyung, Klann, Eric, Chung, Jin Mo, Chung, Kyungsoon
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Antioxidants - metabolism; Capsaicin - adverse effects; Ditiocarb - administration & dosage; Ditiocarb - analogs & derivatives; Dose-Response Relationship, Drug; Foot - physiopathology; Free Radical Scavengers - administration & dosage; Hyperalgesia - chemically induced; Hyperalgesia - metabolism; Hyperalgesia - prevention & control; Male; Metalloporphyrins - administration & dosage; Mice; Mice, Knockout; Mitochondria - drug effects; Mitochondria - metabolism; Pain - chemically induced; Pain - metabolism; Pain - pathology; Pain Measurement - methods; Pain Threshold - drug effects; Pain Threshold - physiology; Reactive Oxygen Species - metabolism; Spinal Cord - pathology; Spinal Cord - ultrastructure; Stilbamidines; Superoxide Dismutase - deficiency; Superoxide Dismutase - metabolism
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.3792-08.2009

Reactive oxygen species (ROS) scavengers have been shown to relieve persistent pain; however, the mechanism is not clearly understood. 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.