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.