title: A peroxynitrite decomposition catalyst prevents mechanical allodynia and NMDA receptor activation in the hind-paw ischemia reperfusion injury rats.
abstract: 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.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Kyungpook National University Hospital, Daegu 700-721, Republic of Korea.
authors.forename: Kyung-Hwa
authors.initials: KH
authors.lastname: Kwak
authors.affiliation: Department of Anesthesiology and Pain Medicine, Kyungpook National University Hospital, Daegu 700-721, Republic of Korea.
authors.forename: Hoon
authors.initials: H
authors.lastname: Jung
authors.affiliation: Department of Anesthesiology and Pain Medicine, Kyungpook National University Hospital, Daegu 700-721, Republic of Korea.
authors.forename: Jun Mo
authors.initials: JM
authors.lastname: Park
authors.affiliation: Department of Anesthesiology and Pain Medicine, Kyungpook National University Hospital, Daegu 700-721, Republic of Korea.
authors.forename: Jin-Seok
authors.initials: JS
authors.lastname: Yeo
authors.affiliation: Department of Anesthesiology and Pain Medicine, Keimyung University Dongsan Medical Center, Daegu 700-721, Republic of Korea.
authors.forename: Hyunjee
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Anesthesiology and Pain Medicine, Kyungpook National University Hospital, Daegu 700-721, Republic of Korea.
authors.forename: Hyung Chul
authors.initials: HC
authors.lastname: Lee
authors.affiliation: Department of Anesthesiology and Pain Medicine, Kyungpook National University Hospital, Daegu 700-721, Republic of Korea.
authors.forename: Sung Hye
authors.initials: SH
authors.lastname: Byun
authors.affiliation: Department of Anesthesiology and Pain Medicine, Kyungpook National University Hospital, Daegu 700-721, Republic of Korea.
authors.forename: Jong-Chan
authors.initials: JC
authors.lastname: Kim
authors.affiliation: Department of Anesthesiology and Pain Medicine, Kyungpook National University Hospital, Daegu 700-721, Republic of Korea.
authors.forename: Sung-Sik
authors.initials: SS
authors.lastname: Park
authors.affiliation: Department of Anesthesiology and Pain Medicine, Kyungpook National University Hospital, Daegu 700-721, Republic of Korea.
authors.forename: Dong Gun
authors.initials: DG
authors.lastname: Lim
keywords: ischemia/reperfusion injury; neuropathic pain; reactive oxygen species