A peroxynitrite decomposition catalyst prevents mechanical allodynia and NMDA receptor activation in the hind-paw ischemia reperfusion injury rats

作者：Kwak Kyung Hwa; Jung Hoon; Park Jun Mo; Yeo Jin Seok; Kim Hyunjee; Lee Hyung Chul; Byun Sung Hye; Kim Jong Chan; Park Sung Sik; Lim Dong Gun^*

来源：Experimental and Therapeutic Medicine, 2014, 7(2): 508-512.

DOI：10.3892/etm.2013.1440

• ischemia/reperfusion injury
• neuropathic pain
• reactive oxygen species

The contributions of superoxide and nitric oxide to ischemia/reperfusion (I/R)-induced neuropathic pain have previously been demonstrated in an animal model that mimics the symptoms of complex regional pain syndrome type I (CRPS I). Targeting peroxynitrite, which is the product of their interaction, may provide effective treatments for I/R-induced neuropathic pain. In this study, the effect of the peroxynitrite decomposition catalyst FeTMPyP [5,10,15,20-tetrakis (N-methyl-4 '-pyridyl)porphyrinato iron (III)], administered at doses of 1, 3 and 10 mg/kg via intraperitoneal injection 30 min prior to reperfusion, was evaluated in rats with chronic post-ischemic pain. The pain behavior of the rats was tested with a von Frey filament. Phosphorylation of N-methyl-D-aspartate (NMDA) receptors in the L4/6 section of the spinal cord was measured on the third day following reperfusion by western blotting. The rats treated with 3 or 10 mg/kg FeTMPyP demonstrated significant increases in their paw withdrawal thresholds and decreased levels of phosphorylated NMDA receptor subunit 1 compared with those of the vehicle group (all P<0.001). These findings suggest that nitrosative stress, specifically that associated with peroxynitrite, may be involved in the mechanical allodynia and central sensitization that are associated with CRPS I and may provide a rationale for CRPS I treatment strategies using peroxynitrite decomposition catalysts.

• 出版日期2014-2