The role of reactive oxygen species in capsaicin-induced mechanical hyperalgesia and in the activities of dorsal horn neurons.
Previous findings that reactive oxygen species (ROS) are involved in neuropathic pain, mainly through spinal mechanisms, suggest that ROS may be involved in central sensitization. To investigate the possible role of ROS in central sensitization, we examined in rats the effects of ROS scavengers on capsaicin-induced secondary hyperalgesia, which is known to be mediated by central sensitization. We used two different ROS scavengers: phenyl N-tert-butylnitrone (PBN) and 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPOL). Intradermal capsaicin injection (20 microg in 20 microl olive oil) into the hind paw produced primary and secondary hyperalgesia. A systemic administration of PBN (100mg/kg, i.p.) or TEMPOL (200mg/kg, i.p.) alleviated capsaicin-induced secondary, but not primary, hyperalgesia. Intrathecal injection of PBN (1mg inof veterinary Surgery/anesthesiology, College of veterinary Medic 50 microl saline) greatly reduced hyperalgesia, whereas intracerebroventricular or intradermal injection of PBN produced only a minor analgesic effect, suggesting that PBN takes effect mainly through the spinal cord. Electrophysiological recordings from wide dynamic range (WDR) neurons in the dorsal horn showed that intradermal capsaicin enhanced the evoked responses to peripheral stimuli; systemic PBN or TEMPOL restored the responses to normal levels. Removal of ROS thus restored the responsiveness of spinal WDR neurons to normal levels, suggesting that ROS is involved in central sensitization, at least in part by sensitizing WDR neurons.
Lee
Inhyung
I
Department of Neuroscience and Cell Biology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1069, USA.
Kim
Hee Kee
HK
Kim
Jae Hyo
JH
Chung
Kyungsoon
K
Chung
Jin Mo
JM
D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001522:Behavior, Animal; D002211:Capsaicin; D003497:Cyclic N-Oxides / Q000627:therapeutic use; D004195:Disease Models, Animal; D004347:Drug Interactions; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008297:Male; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D020671:Posterior Horn Cells / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013113:Spin Labels; D013997:Time Factors
D000975:Antioxidants; D003497:Cyclic N-Oxides; D017382:Reactive Oxygen Species; D013113:Spin Labels; C029217:phenyl-N-tert-butylnitrone; D002211:Capsaicin; C001803:tempol