Unveiling targets for treating postoperative pain: the role of the TNF-α/p38 MAPK/NF-κB/Nav1.8 and Nav1.9 pathways in the mouse model of incisional pain
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
Texto Completo: | https://www.arca.fiocruz.br/handle/icict/56920 |
Resumo: | Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB). Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). Fundação Oswaldo Cruz. |
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Lima, Flávia Oliveira deLauria, Pedro Santana SalesEspírito-Santo, Renan Fernandes doEvangelista, Afrânio FerreiraNogueira, Tâmara Magalhães OliveiraAraldi, DionéiaSoares, Milena Botelho PereiraVillarreal, Cristiane Flora2023-02-07T14:24:51Z2023-02-07T14:24:51Z2022LIMA, Flávia Oliveira de et al. Unveiling targets for treating postoperative pain: the role of the TNF-α/p38 MAPK/NF-κB/Nav1.8 and Nav1.9 pathways in the mouse model of incisional pain. International Journal of Molecular Sciences, v. 23, p. 1-17, 2022.1422-0067https://www.arca.fiocruz.br/handle/icict/5692010.3390/ijms231911630Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB). Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). Fundação Oswaldo Cruz.Universidade Estadual de Feira de Santana. Departamento de Saúde. Feira de Santana, BA, Brasil.Universidade Federal da Bahia. Escola de Farmácia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Centro Universitário SENAI/CIMATEC. Instituto SENAI de Inovação em Sistemas Avançados de Saúde. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Universidade de Campinas. Instituto de Biologia. Departamento de Biologia Estrutural e Funcional. Campinas, SP, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Centro Universitário SENAI/CIMATEC. Instituto SENAI de Inovação em Sistemas Avançados de Saúde. Salvador, BA, Brasil.Universidade Federal da Bahia. Escola de Farmácia. Salvador, BA, Brasil.Although the mouse model of incisional pain is broadly used, the mechanisms underlying plantar incision-induced nociception are not fully understood. This work investigates the role of Nav1.8 and Nav1.9 sodium channels in nociceptive sensitization following plantar incision in mice and the signaling pathway modulating these channels. A surgical incision was made in the plantar hind paw of male Swiss mice. Nociceptive thresholds were assessed by von Frey filaments. Gene ex pression of Nav1.8, Nav1.9, TNF-α, and COX-2 was evaluated by Real-Time PCR in dorsal root ganglia (DRG). Knockdown mice for Nav1.8 and Nav1.9 were produced by antisense oligodeoxynucleotides intrathecal treatments. Local levels of TNF-α and PGE2 were immunoenzymatically determined. Incised mice exhibited hypernociception and upregulated expression of Nav1.8 and Nav1.9 in DRG. Antisense oligodeoxynucleotides reduced hypernociception and downregulated Nav1.8 and Nav1.9. TNF-α and COX-2/PGE2 were upregulated in DRG and plantar skin. Inhibition of TNF-α and COX-2 reduced hypernociception, but only TNF-α inhibition downregulated Nav1.8 and Nav1.9. Antagoniz ing NF-κB and p38 mitogen-activated protein kinase (MAPK), but not ERK or JNK, reduced both hypernociception and hyperexpression of Nav1.8 and Nav1.9. This study proposes the contribution of the TNF-α/p38/NF-κB/Nav1.8 and Nav1.9 pathways to the pathophysiology of the mouse model of incisional pain.engMDPIDor pós-operatóriap38MAPKNF-κBTNF-aCanais de sódio controlados por voltagemPostoperative painp38 MAPKNF-κBTNF-αVoltage-gated sodium channelsDor pós-operatóriaProteínas Quinases p38 Ativadas por MitógenoInibidores do Fator de Necrose TumoralUnveiling targets for treating postoperative pain: the role of the TNF-α/p38 MAPK/NF-κB/Nav1.8 and Nav1.9 pathways in the mouse model of incisional paininfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/56920/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALLima, F.O. Unveiling Targets for Treating..2022.pdfLima, F.O. Unveiling Targets for Treating..2022.pdfapplication/pdf2209204https://www.arca.fiocruz.br/bitstream/icict/56920/2/Lima%2c%20F.O.%20Unveiling%20Targets%20for%20Treating..2022.pdf7412a124169c22853a8dbdcad67778d7MD52icict/569202023-03-15 14:32:51.911oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-03-15T17:32:51Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
dc.title.en_US.fl_str_mv |
Unveiling targets for treating postoperative pain: the role of the TNF-α/p38 MAPK/NF-κB/Nav1.8 and Nav1.9 pathways in the mouse model of incisional pain |
title |
Unveiling targets for treating postoperative pain: the role of the TNF-α/p38 MAPK/NF-κB/Nav1.8 and Nav1.9 pathways in the mouse model of incisional pain |
spellingShingle |
Unveiling targets for treating postoperative pain: the role of the TNF-α/p38 MAPK/NF-κB/Nav1.8 and Nav1.9 pathways in the mouse model of incisional pain Lima, Flávia Oliveira de Dor pós-operatória p38MAPK NF-κB TNF-a Canais de sódio controlados por voltagem Postoperative pain p38 MAPK NF-κB TNF-α Voltage-gated sodium channels Dor pós-operatória Proteínas Quinases p38 Ativadas por Mitógeno Inibidores do Fator de Necrose Tumoral |
title_short |
Unveiling targets for treating postoperative pain: the role of the TNF-α/p38 MAPK/NF-κB/Nav1.8 and Nav1.9 pathways in the mouse model of incisional pain |
title_full |
Unveiling targets for treating postoperative pain: the role of the TNF-α/p38 MAPK/NF-κB/Nav1.8 and Nav1.9 pathways in the mouse model of incisional pain |
title_fullStr |
Unveiling targets for treating postoperative pain: the role of the TNF-α/p38 MAPK/NF-κB/Nav1.8 and Nav1.9 pathways in the mouse model of incisional pain |
title_full_unstemmed |
Unveiling targets for treating postoperative pain: the role of the TNF-α/p38 MAPK/NF-κB/Nav1.8 and Nav1.9 pathways in the mouse model of incisional pain |
title_sort |
Unveiling targets for treating postoperative pain: the role of the TNF-α/p38 MAPK/NF-κB/Nav1.8 and Nav1.9 pathways in the mouse model of incisional pain |
author |
Lima, Flávia Oliveira de |
author_facet |
Lima, Flávia Oliveira de Lauria, Pedro Santana Sales Espírito-Santo, Renan Fernandes do Evangelista, Afrânio Ferreira Nogueira, Tâmara Magalhães Oliveira Araldi, Dionéia Soares, Milena Botelho Pereira Villarreal, Cristiane Flora |
author_role |
author |
author2 |
Lauria, Pedro Santana Sales Espírito-Santo, Renan Fernandes do Evangelista, Afrânio Ferreira Nogueira, Tâmara Magalhães Oliveira Araldi, Dionéia Soares, Milena Botelho Pereira Villarreal, Cristiane Flora |
author2_role |
author author author author author author author |
dc.contributor.author.fl_str_mv |
Lima, Flávia Oliveira de Lauria, Pedro Santana Sales Espírito-Santo, Renan Fernandes do Evangelista, Afrânio Ferreira Nogueira, Tâmara Magalhães Oliveira Araldi, Dionéia Soares, Milena Botelho Pereira Villarreal, Cristiane Flora |
dc.subject.other.en_US.fl_str_mv |
Dor pós-operatória p38MAPK NF-κB TNF-a Canais de sódio controlados por voltagem |
topic |
Dor pós-operatória p38MAPK NF-κB TNF-a Canais de sódio controlados por voltagem Postoperative pain p38 MAPK NF-κB TNF-α Voltage-gated sodium channels Dor pós-operatória Proteínas Quinases p38 Ativadas por Mitógeno Inibidores do Fator de Necrose Tumoral |
dc.subject.en.en_US.fl_str_mv |
Postoperative pain p38 MAPK NF-κB TNF-α Voltage-gated sodium channels |
dc.subject.decs.en_US.fl_str_mv |
Dor pós-operatória Proteínas Quinases p38 Ativadas por Mitógeno Inibidores do Fator de Necrose Tumoral |
description |
Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB). Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). Fundação Oswaldo Cruz. |
publishDate |
2022 |
dc.date.issued.fl_str_mv |
2022 |
dc.date.accessioned.fl_str_mv |
2023-02-07T14:24:51Z |
dc.date.available.fl_str_mv |
2023-02-07T14:24:51Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
LIMA, Flávia Oliveira de et al. Unveiling targets for treating postoperative pain: the role of the TNF-α/p38 MAPK/NF-κB/Nav1.8 and Nav1.9 pathways in the mouse model of incisional pain. International Journal of Molecular Sciences, v. 23, p. 1-17, 2022. |
dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/56920 |
dc.identifier.issn.en_US.fl_str_mv |
1422-0067 |
dc.identifier.doi.none.fl_str_mv |
10.3390/ijms231911630 |
identifier_str_mv |
LIMA, Flávia Oliveira de et al. Unveiling targets for treating postoperative pain: the role of the TNF-α/p38 MAPK/NF-κB/Nav1.8 and Nav1.9 pathways in the mouse model of incisional pain. International Journal of Molecular Sciences, v. 23, p. 1-17, 2022. 1422-0067 10.3390/ijms231911630 |
url |
https://www.arca.fiocruz.br/handle/icict/56920 |
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eng |
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eng |
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