Korean J Anesthesiol.  2012 Aug;63(2):149-156. 10.4097/kjae.2012.63.2.149.

Effect of superoxide on the development and maintenance of mechanical allodynia in a rat model of chronic post-ischemia pain

• Han CG
• Han JK
• Park KB
• Kwak KH
• Park SS
• Lim DG

• KMID: 1780197
• DOI: http://doi.org/10.4097/kjae.2012.63.2.149

Abstract

BACKGROUND
Reactive oxygen species and inflammatory responses contribute to the development of neuropathic pain. Superoxide serves to mediate cell signaling processes and tissue injury during inflammation. We examined the effects of superoxide on the development and maintenance of mechanical allodynia, as well as its contribution to central sensitization in a superoxide-rich animal model of neuropathic pain.
METHODS
Chronic post-ischemia pain (CPIP) was induced via the left hindpaw ischemia for 3 h, followed by reperfusion. Superoxide dismutase (4,000 U/kg, i.p.) was administered either 5 min before ischemia (BI), 5 min before reperfusion (BR), or 3 days after reperfusion (3AR). Withdrawal thresholds of the four paws were measured to assess the mechanical allodynia and the effects of circulating xanthine oxidase (XO)-mediated superoxide production. In addition, we measured the levels of N-methyl D-aspartate receptor subunit 1 phosphorylation (p-NR1) in the ipsilateral and contralateral spinal cord (L4-6), by Western blotting, to examine the superoxide-mediated central sensitization. Superoxide production was assessed by allopurinol-sensitive, XO-mediated lipid peroxidation of the spinal cord and gastrocnemius muscles.
RESULTS
Withdrawal thresholds of forepaws did not vary across the 7 days of testing. In the hindpaws, both ipsilateral and contralateral mechanical allodynia was most attenuated in the BR group, followed by the BI and 3AR groups. The degree of NR1 activation was in contrast to the changes in the withdrawal thresholds.
CONCLUSIONS
These data suggest that superoxide is involved in the development and maintenance of mechanical allodynia, particularly via central sensitization in the spinal cord.

Keyword

Chronic post-ischemia pain; Complex regional pain syndrome; Mechanical allodynia; Neuropathic pain; Reactive oxygen species; Superoxide

MeSH Terms

Animals
Blotting, Western
Central Nervous System Sensitization
D-Aspartic Acid
Hyperalgesia
Inflammation
Ischemia
Lipid Peroxidation
Models, Animal
Neuralgia
Phosphorylation
Rats
Reactive Oxygen Species
Reperfusion
Spinal Cord
Superoxide Dismutase
Superoxides
Xanthine Oxidase
D-Aspartic Acid
Reactive Oxygen Species
Superoxide Dismutase
Superoxides
Xanthine Oxidase