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The superoxide anion donor, potassium superoxide, induces pain and inflammation in mice through production of reactive oxygen species and cyclooxygenase-2

It is currently accepted that superoxide anion (O(2) (•−)) is an important mediator in pain and inflammation. The role of superoxide anion in pain and inflammation has been mainly determined indirectly by modulating its production and inactivation. Direct evidence using potassium superoxide (KO(2)),...

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Autores principales: Maioli, N.A., Zarpelon, A.C., Mizokami, S.S., Calixto-Campos, C., Guazelli, C.F.S., Hohmann, M.S.N., Pinho-Ribeiro, F.A., Carvalho, T.T., Manchope, M.F., Ferraz, C.R., Casagrande, R., Verri, W.A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Associação Brasileira de Divulgação Científica 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4418362/
https://www.ncbi.nlm.nih.gov/pubmed/25714890
http://dx.doi.org/10.1590/1414-431X20144187
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author Maioli, N.A.
Zarpelon, A.C.
Mizokami, S.S.
Calixto-Campos, C.
Guazelli, C.F.S.
Hohmann, M.S.N.
Pinho-Ribeiro, F.A.
Carvalho, T.T.
Manchope, M.F.
Ferraz, C.R.
Casagrande, R.
Verri, W.A.
author_facet Maioli, N.A.
Zarpelon, A.C.
Mizokami, S.S.
Calixto-Campos, C.
Guazelli, C.F.S.
Hohmann, M.S.N.
Pinho-Ribeiro, F.A.
Carvalho, T.T.
Manchope, M.F.
Ferraz, C.R.
Casagrande, R.
Verri, W.A.
author_sort Maioli, N.A.
collection PubMed
description It is currently accepted that superoxide anion (O(2) (•−)) is an important mediator in pain and inflammation. The role of superoxide anion in pain and inflammation has been mainly determined indirectly by modulating its production and inactivation. Direct evidence using potassium superoxide (KO(2)), a superoxide anion donor, demonstrated that it induced thermal hyperalgesia, as assessed by the Hargreaves method. However, it remains to be determined whether KO(2) is capable of inducing other inflammatory and nociceptive responses attributed to superoxide anion. Therefore, in the present study, we investigated the nociceptive and inflammatory effects of KO(2). The KO(2)-induced inflammatory responses evaluated in mice were: mechanical hyperalgesia (electronic version of von Frey filaments), thermal hyperalgesia (hot plate), edema (caliper rule), myeloperoxidase activity (colorimetric assay), overt pain-like behaviors (flinches, time spent licking and writhing score), leukocyte recruitment, oxidative stress, and cyclooxygenase-2 mRNA expression (quantitative PCR). Administration of KO(2) induced mechanical hyperalgesia, thermal hyperalgesia, paw edema, leukocyte recruitment, the writhing response, paw flinching, and paw licking in a dose-dependent manner. KO(2) also induced time-dependent cyclooxygenase-2 mRNA expression in the paw skin. The nociceptive, inflammatory, and oxidative stress components of KO(2)-induced responses were responsive to morphine (analgesic opioid), quercetin (antioxidant flavonoid), and/or celecoxib (anti-inflammatory cyclooxygenase-2 inhibitor) treatment. In conclusion, the well-established superoxide anion donor KO(2) is a valuable tool for studying the mechanisms and pharmacological susceptibilities of superoxide anion-triggered nociceptive and inflammatory responses ranging from mechanical and thermal hyperalgesia to overt pain-like behaviors, edema, and leukocyte recruitment.
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spelling pubmed-44183622015-05-15 The superoxide anion donor, potassium superoxide, induces pain and inflammation in mice through production of reactive oxygen species and cyclooxygenase-2 Maioli, N.A. Zarpelon, A.C. Mizokami, S.S. Calixto-Campos, C. Guazelli, C.F.S. Hohmann, M.S.N. Pinho-Ribeiro, F.A. Carvalho, T.T. Manchope, M.F. Ferraz, C.R. Casagrande, R. Verri, W.A. Braz J Med Biol Res Biomedical Sciences It is currently accepted that superoxide anion (O(2) (•−)) is an important mediator in pain and inflammation. The role of superoxide anion in pain and inflammation has been mainly determined indirectly by modulating its production and inactivation. Direct evidence using potassium superoxide (KO(2)), a superoxide anion donor, demonstrated that it induced thermal hyperalgesia, as assessed by the Hargreaves method. However, it remains to be determined whether KO(2) is capable of inducing other inflammatory and nociceptive responses attributed to superoxide anion. Therefore, in the present study, we investigated the nociceptive and inflammatory effects of KO(2). The KO(2)-induced inflammatory responses evaluated in mice were: mechanical hyperalgesia (electronic version of von Frey filaments), thermal hyperalgesia (hot plate), edema (caliper rule), myeloperoxidase activity (colorimetric assay), overt pain-like behaviors (flinches, time spent licking and writhing score), leukocyte recruitment, oxidative stress, and cyclooxygenase-2 mRNA expression (quantitative PCR). Administration of KO(2) induced mechanical hyperalgesia, thermal hyperalgesia, paw edema, leukocyte recruitment, the writhing response, paw flinching, and paw licking in a dose-dependent manner. KO(2) also induced time-dependent cyclooxygenase-2 mRNA expression in the paw skin. The nociceptive, inflammatory, and oxidative stress components of KO(2)-induced responses were responsive to morphine (analgesic opioid), quercetin (antioxidant flavonoid), and/or celecoxib (anti-inflammatory cyclooxygenase-2 inhibitor) treatment. In conclusion, the well-established superoxide anion donor KO(2) is a valuable tool for studying the mechanisms and pharmacological susceptibilities of superoxide anion-triggered nociceptive and inflammatory responses ranging from mechanical and thermal hyperalgesia to overt pain-like behaviors, edema, and leukocyte recruitment. Associação Brasileira de Divulgação Científica 2015-02-13 /pmc/articles/PMC4418362/ /pubmed/25714890 http://dx.doi.org/10.1590/1414-431X20144187 Text en 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, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Biomedical Sciences
Maioli, N.A.
Zarpelon, A.C.
Mizokami, S.S.
Calixto-Campos, C.
Guazelli, C.F.S.
Hohmann, M.S.N.
Pinho-Ribeiro, F.A.
Carvalho, T.T.
Manchope, M.F.
Ferraz, C.R.
Casagrande, R.
Verri, W.A.
The superoxide anion donor, potassium superoxide, induces pain and inflammation in mice through production of reactive oxygen species and cyclooxygenase-2
title The superoxide anion donor, potassium superoxide, induces pain and inflammation in mice through production of reactive oxygen species and cyclooxygenase-2
title_full The superoxide anion donor, potassium superoxide, induces pain and inflammation in mice through production of reactive oxygen species and cyclooxygenase-2
title_fullStr The superoxide anion donor, potassium superoxide, induces pain and inflammation in mice through production of reactive oxygen species and cyclooxygenase-2
title_full_unstemmed The superoxide anion donor, potassium superoxide, induces pain and inflammation in mice through production of reactive oxygen species and cyclooxygenase-2
title_short The superoxide anion donor, potassium superoxide, induces pain and inflammation in mice through production of reactive oxygen species and cyclooxygenase-2
title_sort superoxide anion donor, potassium superoxide, induces pain and inflammation in mice through production of reactive oxygen species and cyclooxygenase-2
topic Biomedical Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4418362/
https://www.ncbi.nlm.nih.gov/pubmed/25714890
http://dx.doi.org/10.1590/1414-431X20144187
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