| Reactive oxygen species and N-methyl-D-aspartate receptor-mediated central sensitization in hindlimb ischemia/reperfusion injury-induced neuropathic pain rats. |
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Kwang Woo Kim, Mi Jin Ha, Kyung Young Jung, Kyung Hwa Kwak, Sung Sik Park, Dong Gun Lim |
1Soo Pain Clinic, Busan, Korea.
2Department of Anesthesiology and Pain Medicine, School of Medicine, Kyungpook National University, Daegu, Korea. dglim@knu.ac.kr |
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| Abstract |
BACKGROUND
Reactive oxygen species (ROS) contribute to development of neuropathic pain. A neuropathic pain syndrome was produced in rats following prolonged hindpaw ischemia/reperfusion injury, creating an animal model of complex regional pain syndrome-Type I (CRPS-I). This study was designed to evaluate the validity of this model for ROS and pain research. Herein we show superoxide produces N-methyl-D-aspartate (NMDA) mediated mechanical allodynia.
METHODS
Male adult SD rats were used for neuropathic pain model. Plasma superoxide production rates of before ischemia (BI) and 5 min after reperfusion (JR) were measured via cytochrome C reduction in the presence of xanthine (without xanthine oxidase, kinetics, 550 nm). Mechanical allodynia was measured in both hindpaws. Activation of NMDA receptor subunit 1 (P-NR1) of lumbar spinal cord (L4-L6) in accordance with the change of allodynia was analyzed by the Western blot.
RESULTS
Allopurinol-inhibitable, xanthine oxidase-mediated plasma superoxide production was increased at AR. Mechanical allodynia was present in both hindpaws as early as 1 hr after reperfusion, and lasted at least 1 week. The expression of P-NR1 was the highest at 3 days after reperfusion when the withdrawal threshold was the lowest point. SOD significantly blocked P-NR1 activation.
CONCLUSIONS
This study suggests that ischemia/reperfusion injury induced neuropathic pain model is a good candidate for the research fields of ROS and pain mechanism. The generation of ROS, especially superoxide is partly responsible for NMDA-mediated mechanical allodynia. |
| Key Words:
Allodynia; Neuropathic pain; Superoxide |
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