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Korean Journal of Anesthesiology 2009;56(2):186-194.
DOI: https://doi.org/10.4097/kjae.2009.56.2.186   
Reactive oxygen species and N-methyl-D-aspartate receptor-mediated central sensitization in hindlimb ischemia/reperfusion injury-induced neuropathic pain rats.
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
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.
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.
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.
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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