TY - JOUR
T1 - Reactive oxygen species (ROS) are involved in enhancement of NMDA-receptor phosphorylation in animal models of pain
AU - Gao, Xiu
AU - Kim, Hee Kee
AU - Chung, Jin Mo
AU - Chung, Kyungsoon
N1 - Funding Information:
This work was supported by National Institutes of Health Grants NS11255, NS31680, and AT001474. We would like to thank Ms. Denise Broker for her excellent service in English editing.
PY - 2007/10
Y1 - 2007/10
N2 - Recent studies indicate that reactive oxygen species (ROS) play an important role in neuropathic pain, predominantly through spinal mechanisms. Since the data suggest that ROS are involved in central sensitization, the present study examines the levels of activated N-methyl-d-aspartate (NMDA) receptors in the dorsal horn before and after removal of ROS with a ROS scavenger, phenyl-N-t-butyl nitrone (PBN), in animal models of pain. Tight ligation of the L5 spinal nerve was used for the neuropathic pain model and intradermal injection of capsaicin was used for the inflammatory pain model. Foot withdrawal thresholds to von Frey stimuli to the paw were measured as pain indicators. The number of neurons showing immunoreactivity to phosphorylated NMDA-receptor subunit 1 (pNR1) and the total amount of pNR1 proteins in the spinal cord were determined using immunohistochemical and Western blotting techniques, respectively. Hyperalgesia and increased pNR1 expression were observed in both neuropathic and capsaicin-treated rats. A systemic injection of PBN (100 mg/kg, i.p.) dramatically reduced hyperalgesia and blocked the enhancement of spinal pNR1 in both pain models within 1 h after PBN treatment. The data suggest that ROS are involved in NMDA-receptor activation, an essential step in central sensitization, and thus contribute to neuropathic and capsaicin-induced pain.
AB - Recent studies indicate that reactive oxygen species (ROS) play an important role in neuropathic pain, predominantly through spinal mechanisms. Since the data suggest that ROS are involved in central sensitization, the present study examines the levels of activated N-methyl-d-aspartate (NMDA) receptors in the dorsal horn before and after removal of ROS with a ROS scavenger, phenyl-N-t-butyl nitrone (PBN), in animal models of pain. Tight ligation of the L5 spinal nerve was used for the neuropathic pain model and intradermal injection of capsaicin was used for the inflammatory pain model. Foot withdrawal thresholds to von Frey stimuli to the paw were measured as pain indicators. The number of neurons showing immunoreactivity to phosphorylated NMDA-receptor subunit 1 (pNR1) and the total amount of pNR1 proteins in the spinal cord were determined using immunohistochemical and Western blotting techniques, respectively. Hyperalgesia and increased pNR1 expression were observed in both neuropathic and capsaicin-treated rats. A systemic injection of PBN (100 mg/kg, i.p.) dramatically reduced hyperalgesia and blocked the enhancement of spinal pNR1 in both pain models within 1 h after PBN treatment. The data suggest that ROS are involved in NMDA-receptor activation, an essential step in central sensitization, and thus contribute to neuropathic and capsaicin-induced pain.
KW - Central sensitization
KW - Free radical
KW - Hyperalgesia
KW - NMDA-receptor activation
KW - PBN
KW - Spinal dorsal horn neuron
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U2 - 10.1016/j.pain.2007.01.011
DO - 10.1016/j.pain.2007.01.011
M3 - Article
C2 - 17317010
AN - SCOPUS:34548492281
SN - 0304-3959
VL - 131
SP - 262
EP - 271
JO - Pain
JF - Pain
IS - 3
ER -