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Superoxide and Nitric Oxide Involvement in Enhancing of N-methyl-D-aspartate Receptor-Mediated Central Sensitization in the Chronic Post-ischemia Pain Model
BACKGROUND: Recent studies indicate that reactive oxygen species (ROS) are involved in persistent pain, including neuropathic and inflammatory pain. Since the data suggest that ROS are involved in central sensitization, the present study examines the levels of activated N-methyl-D-aspartate (NMDA) r...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Korean Pain Society
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2884210/ https://www.ncbi.nlm.nih.gov/pubmed/20552066 http://dx.doi.org/10.3344/kjp.2010.23.1.1 |
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author | Ryu, Tae Ha Jung, Kyung Young Ha, Mi Jin Kwak, Kyung Hwa Lim, Dong Gun Hong, Jung Gil |
author_facet | Ryu, Tae Ha Jung, Kyung Young Ha, Mi Jin Kwak, Kyung Hwa Lim, Dong Gun Hong, Jung Gil |
author_sort | Ryu, Tae Ha |
collection | PubMed |
description | BACKGROUND: Recent studies indicate that reactive oxygen species (ROS) are involved in persistent pain, including neuropathic and inflammatory pain. Since the data suggest that ROS are involved in central sensitization, the present study examines the levels of activated N-methyl-D-aspartate (NMDA) receptors in the dorsal horn after an exogenous supply of three antioxidants in rats with chronic post-ischemia pain (CPIP). This serves as an animal model of complex regional pain syndrome type-I induced by hindpaw ischemia/reperfusion injury. METHODS: The application of tight-fitting O-rings for a period of three hours produced CPIP in male Sprague-Dawley rats. Allopurinol 4 mg/kg, allopurinol 40 mg/kg, superoxide dismutase (SOD) 4,000 U/kg, N-nitro-L-arginine methyl ester (L-NAME) 10 mg/kg and SOD 4,000 U/kg plus L-NAME 10 mg/kg were administered intraperitoneally just after O-ring application and on the first and second days after reperfusion. Mechanical allodynia was measured, and activation of the NMDA receptor subunit 1 (pNR1) of the lumbar spinal cord (L4-L6) was analyzed by the Western blot three days after reperfusion. RESULTS: Allopurinol reduced mechanical allodynia and attenuated the enhancement of spinal pNR1 expression in CPIP rats. SOD and L-NAME also blocked spinal pNR1 in accordance with the reduced mechanical allodynia in rats with CPIP. CONCLUSIONS: The present data suggest the contribution of superoxide, produced via xanthine oxidase, and the participation of superoxide and nitric oxide as a precursor of peroxynitrite in NMDA mediated central sensitization. Finally, the findings support a therapeutic potential for the manipulation of superoxide and nitric oxide in ischemia/reperfusion related pain conditions. |
format | Text |
id | pubmed-2884210 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The Korean Pain Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-28842102010-06-15 Superoxide and Nitric Oxide Involvement in Enhancing of N-methyl-D-aspartate Receptor-Mediated Central Sensitization in the Chronic Post-ischemia Pain Model Ryu, Tae Ha Jung, Kyung Young Ha, Mi Jin Kwak, Kyung Hwa Lim, Dong Gun Hong, Jung Gil Korean J Pain Original Article BACKGROUND: Recent studies indicate that reactive oxygen species (ROS) are involved in persistent pain, including neuropathic and inflammatory pain. Since the data suggest that ROS are involved in central sensitization, the present study examines the levels of activated N-methyl-D-aspartate (NMDA) receptors in the dorsal horn after an exogenous supply of three antioxidants in rats with chronic post-ischemia pain (CPIP). This serves as an animal model of complex regional pain syndrome type-I induced by hindpaw ischemia/reperfusion injury. METHODS: The application of tight-fitting O-rings for a period of three hours produced CPIP in male Sprague-Dawley rats. Allopurinol 4 mg/kg, allopurinol 40 mg/kg, superoxide dismutase (SOD) 4,000 U/kg, N-nitro-L-arginine methyl ester (L-NAME) 10 mg/kg and SOD 4,000 U/kg plus L-NAME 10 mg/kg were administered intraperitoneally just after O-ring application and on the first and second days after reperfusion. Mechanical allodynia was measured, and activation of the NMDA receptor subunit 1 (pNR1) of the lumbar spinal cord (L4-L6) was analyzed by the Western blot three days after reperfusion. RESULTS: Allopurinol reduced mechanical allodynia and attenuated the enhancement of spinal pNR1 expression in CPIP rats. SOD and L-NAME also blocked spinal pNR1 in accordance with the reduced mechanical allodynia in rats with CPIP. CONCLUSIONS: The present data suggest the contribution of superoxide, produced via xanthine oxidase, and the participation of superoxide and nitric oxide as a precursor of peroxynitrite in NMDA mediated central sensitization. Finally, the findings support a therapeutic potential for the manipulation of superoxide and nitric oxide in ischemia/reperfusion related pain conditions. The Korean Pain Society 2010-03 2010-03-10 /pmc/articles/PMC2884210/ /pubmed/20552066 http://dx.doi.org/10.3344/kjp.2010.23.1.1 Text en Copyright © The Korean Pain Society, 2010 http://creativecommons.org/licenses/by-nc/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Ryu, Tae Ha Jung, Kyung Young Ha, Mi Jin Kwak, Kyung Hwa Lim, Dong Gun Hong, Jung Gil Superoxide and Nitric Oxide Involvement in Enhancing of N-methyl-D-aspartate Receptor-Mediated Central Sensitization in the Chronic Post-ischemia Pain Model |
title | Superoxide and Nitric Oxide Involvement in Enhancing of N-methyl-D-aspartate Receptor-Mediated Central Sensitization in the Chronic Post-ischemia Pain Model |
title_full | Superoxide and Nitric Oxide Involvement in Enhancing of N-methyl-D-aspartate Receptor-Mediated Central Sensitization in the Chronic Post-ischemia Pain Model |
title_fullStr | Superoxide and Nitric Oxide Involvement in Enhancing of N-methyl-D-aspartate Receptor-Mediated Central Sensitization in the Chronic Post-ischemia Pain Model |
title_full_unstemmed | Superoxide and Nitric Oxide Involvement in Enhancing of N-methyl-D-aspartate Receptor-Mediated Central Sensitization in the Chronic Post-ischemia Pain Model |
title_short | Superoxide and Nitric Oxide Involvement in Enhancing of N-methyl-D-aspartate Receptor-Mediated Central Sensitization in the Chronic Post-ischemia Pain Model |
title_sort | superoxide and nitric oxide involvement in enhancing of n-methyl-d-aspartate receptor-mediated central sensitization in the chronic post-ischemia pain model |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2884210/ https://www.ncbi.nlm.nih.gov/pubmed/20552066 http://dx.doi.org/10.3344/kjp.2010.23.1.1 |
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