Superoxide signaling in pain is independent of nitric oxide signaling.
Two reactive oxygen species (ROS), nitric oxide (NO(.)) and superoxide ((.)O2), contribute to persistent pain. Using three different animal models where ROS mediate pain, this study examined whether NO(.) and (.)O2 converge to peroxynitrite (ONOO(-)) or whether each has an independent signaling pathway to produce hyperalgesia. The hyperalgesia after spinal nerve ligation was attenuated by removing (.)O2 by TEMPOL or inhibiting NO(.) production by L-NAME, but not by removing peroxynitrite with FeTMPyP. Nitric oxide-induced hyperalgesia was not affected by removing (.)O2 but was reduced by a guanyl cyclase inhibitor. Superoxide-induced hyperalgesia was not affected by inhibiting NO(.) production but was suppressed by a protein kinase C inhibitor. The data suggest that NO(.) and (.)O2 operate independently to generate pain.
Kim
Hee Young
HY
Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, Texas TX 77555-1069, USA.
Wang
Jigong
J
Lu
Ying
Y
Chung
Jin Mo
JM
Chung
Kyungsoon
K
D000818:Animals; D000968:Antimycin A; D003497:Cyclic N-Oxides / Q000627:therapeutic use; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use; D009437:Neuralgia / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000627:therapeutic use; D009569:Nitric Oxide / Q000378:metabolism*; D009603:Nitroso Compounds; D010147:Pain Measurement / Q000379:methods; D030421:Peroxynitrous Acid / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
C492721:5,10,15,20-tetrakis(N-methyl-4'-pyridyl)porphyrinato-iron(III); D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D008665:Metalloporphyrins; C118603:NOC 12; D018696:Neuroprotective Agents; D009603:Nitroso Compounds; D017382:Reactive Oxygen Species; D013113:Spin Labels; D013481:Superoxides; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D000968:Antimycin A; C001803:tempol; D019331:NG-Nitroarginine Methyl Ester