Korean J Anesthesiol.  2009 Feb;56(2):186-194. 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

• Kim KW
• Ha MJ
• Jung KY
• Kwak KH
• Park SS
• Lim DG

• KMID: 2299316
• DOI: http://doi.org/10.4097/kjae.2009.56.2.186

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.

Keyword

Allodynia; Neuropathic pain; Superoxide

MeSH Terms

Adult
Animals
Blotting, Western
Central Nervous System Sensitization
Cytochromes c
Hindlimb
Humans
Hyperalgesia
Ischemia
Kinetics
Male
Models, Animal
N-Methylaspartate
Neuralgia
Plasma
Rats
Reactive Oxygen Species
Reperfusion
Spinal Cord
Superoxides
Xanthine
Xanthine Oxidase
Cytochromes c
N-Methylaspartate
Reactive Oxygen Species
Superoxides
Xanthine
Xanthine Oxidase