Increased production of mitochondrial superoxide in the spinal cord induces pain behaviors in mice: the effect of mitochondrial electron transport complex inhibitors.
Scavengers of reactive oxygen species (ROS) have been shown to produce a strong antinociceptive effect on persistent pain, and mitochondria are suggested to be the main source of ROS in the spinal dorsal horn. To explore whether excessive generation of mitochondrial superoxide alone can induce pain, the effect of mitochondrial electron transport complex inhibitors on the development of mechanical hyperalgesia was examined in mice. Intrathecal injection of an electron transport complex inhibitor, antimycin A or rotenone, in normal mice resulted in a slowly developing but long-lasting and dose-dependent mechanical hyperalgesia. The levels of mechanical hyperalgesia after antimycin A, a complex III inhibitor, were higher than that with rotenone, a complex I inhibitor. A large increase of mitochondrial superoxide in the spinal dorsal horn and a strong antinociceptive effect of ROS scavengers, phenyl-N-tert-butylnitrone (PBN) and 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) were observed in antimycin A-treated mice. The study indicates that the enhanced production of spinal mitochondrial superoxide alone without nerve injury can produce mechanical hyperalgesia.
Kim
Hee Young
HY
Department of Neuroscience and Cell Biology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1069, USA.
Chung
Jin Mo
JM
Chung
Kyungsoon
K
D000818:Animals; D000968:Antimycin A / Q000009:adverse effects*; D001522:Behavior, Animal; D003497:Cyclic N-Oxides / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000009:adverse effects*; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use; D010146:Pain / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D013113:Spin Labels; D013116:Spinal Cord / Q000187:drug effects / Q000648:ultrastructure*; D013481:Superoxides / Q000378:metabolism*
D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D013113:Spin Labels; D013481:Superoxides; C029217:phenyl-N-tert-butylnitrone; D000968:Antimycin A; C001803:tempol