Envolvimento das prote?nas quinases ativadas por mit?geno e do fator de transcri??o nuclear Kappa B em modelos experimentais de dor muscular inflamat?ria e p?s-operat?ria
Ano de defesa: | 2011 |
---|---|
Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Estadual de Feira de Santana
|
Programa de Pós-Graduação: |
Doutorado Acad?mico em Biotecnologia
|
Departamento: |
DEPARTAMENTO DE CI?NCIAS BIOL?GICAS
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://tede2.uefs.br:8080/handle/tede/1131 |
Resumo: | Chronic pain is often associated with transcriptional and functional changes in neural systems involved in the transmission and modulation of nociceptive information. The transcription of several proteins involved in chronic pain is regulated by the transcription factor ?B (NF?B). Furthermore, NF?B is an important target of MAPKs (Mitogen-Activated Protein Kinase). Therefore, it was investigated the involvement of MAPKs (p38, ERK and JNK) and NF?B in two experimental models of persistent pain: inflammatory muscle pain and postoperative pain models. Pre-treatment with inhibitors of NF?B and MAPKs (p38, ERK and JNK) reduced the acute muscle hypernociception, but not persistent hypernociception. In addition, pharmacological inhibition of NF?B or p38 MAPK but not ERK and JNK, reduced postoperative hypernociception. To investigate the mechanisms by which NF?B contributes to postoperative hypernociception, we analyzed the effect of PDTC, an NF?B inhibitor, on the production of inflammatory mediators and expression of sodium channels involved in nociceptive sensitization. The incision elevated the levels of TNF-? and PGE2 as well as increased the expression of sodium channels Nav 1.8 and 1.9 in sensory neurons, these effects being were neutralized by PDTC. These data suggest that the surgical incision activates the p38 MAPK/NF?B pathway, which increases the expression of TNF-? and PGE2, responsible for the up regulation of sodium channels Nav 1.8 and Nav 1.9 in sensory neuron resulting in neuronal hyperexcitability and postoperative hypernociception. These results provide new evidence on the distinct roles of NF?B and MAPKs in the development of acute and persistent pain, and indicate that NF?B may be an interesting pharmacological target for the treatment of postoperative pain. |
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Villarreal, Cristiane Flora8958036265382466815591http://lattes.cnpq.br/8965167326304855Lima, Fl?via Oliveira de2020-05-15T23:50:59Z2011-12-01LIMA, Fl?via Oliveira de. Envolvimento das prote?nas quinases ativadas por mit?geno e do fator de transcri??o nuclear Kappa B em modelos experimentais de dor muscular inflamat?ria e p?s-operat?ria. 2011. 119 f. Tese (Doutorado Acad?mico em Biotecnologia)- Universidade Estadual de Feira de Santana, Feira de Santana, 2011.http://tede2.uefs.br:8080/handle/tede/1131Chronic pain is often associated with transcriptional and functional changes in neural systems involved in the transmission and modulation of nociceptive information. The transcription of several proteins involved in chronic pain is regulated by the transcription factor ?B (NF?B). Furthermore, NF?B is an important target of MAPKs (Mitogen-Activated Protein Kinase). Therefore, it was investigated the involvement of MAPKs (p38, ERK and JNK) and NF?B in two experimental models of persistent pain: inflammatory muscle pain and postoperative pain models. Pre-treatment with inhibitors of NF?B and MAPKs (p38, ERK and JNK) reduced the acute muscle hypernociception, but not persistent hypernociception. In addition, pharmacological inhibition of NF?B or p38 MAPK but not ERK and JNK, reduced postoperative hypernociception. To investigate the mechanisms by which NF?B contributes to postoperative hypernociception, we analyzed the effect of PDTC, an NF?B inhibitor, on the production of inflammatory mediators and expression of sodium channels involved in nociceptive sensitization. The incision elevated the levels of TNF-? and PGE2 as well as increased the expression of sodium channels Nav 1.8 and 1.9 in sensory neurons, these effects being were neutralized by PDTC. These data suggest that the surgical incision activates the p38 MAPK/NF?B pathway, which increases the expression of TNF-? and PGE2, responsible for the up regulation of sodium channels Nav 1.8 and Nav 1.9 in sensory neuron resulting in neuronal hyperexcitability and postoperative hypernociception. These results provide new evidence on the distinct roles of NF?B and MAPKs in the development of acute and persistent pain, and indicate that NF?B may be an interesting pharmacological target for the treatment of postoperative pain.A dor cr?nica ? frequentemente associada a altera??es transcricionais-funcionais nos sistemas neuronais envolvidos na transmiss?o e modula??o da informa??o nociceptiva. A transcri??o de v?rias prote?nas envolvidas na dor cr?nica ? primorosamente regulada pelo fator de transcri??o nuclear ?B (NF?B). Considerando que o NF?B ? um importante alvo das MAPKs (prote?na quinase ativada por mit?geno), investigamos a participa??o das MAPKs (p38, ERK e JNK) e NF?B em dois modelos experimentais de dor persistente: modelo de dor muscular inflamat?ria e modelo de dor p?s-operat?ria. O pr?-tratamento com inibidores do NF?B, das MAPKs p38, ERK e JNK inibiu a hipernocicep??o muscular aguda, mas n?o a persistente. Em adi??o, a inibi??o farmacol?gica do NF?B ou da MAPK p38, mas n?o da ERK ou JNK, reduziu a hipernocicep??o p?s-operat?ria. Para investigar os mecanismos pelos quais o NF?B contribui para a hipernocicep??o p?s-operat?ria, analisamos o efeito do PDTC, inibidor do NF?B sobre a produ??o de mediadores inflamat?rios e express?o de canais para s?dio envolvidos na sensibiliza??o nociceptiva. Ap?s a incis?o cir?rgica houve um aumento nos n?veis do TNF-? e PGE2, assim como aumento na express?o g?nica de canais para s?dio Nav 1.8 e 1.9 nos neur?nios sensoriais, sendo esses efeitos prevenidos pelo PDTC. Esses dados nos permitem propor que possivelmente a incis?o cir?rgica ativa a via MAPK p38/NF?B que induz aumento da express?o de TNF-? e PGE2, respons?veis pelo aumento da express?o para canais para s?dio Nav 1.8 e Nav 1.9 no neur?nio sensorial, gerando hiperexcitabilidade e hipernocicep??o p?s-operat?ria. Estes resultados fornecem novas evid?ncias sobre os distintos pap?is do NF?B e das MAPKs no desenvolvimento da dor aguda e persistente, e indicam que o NF?B pode ser um alvo farmacol?gico interessante para o tratamento da dor p?s-operat?ria.Submitted by Ricardo Cedraz Duque Moliterno (ricardo.moliterno@uefs.br) on 2020-05-15T23:50:59Z No. of bitstreams: 1 Tese_Flavia.pdf: 1036514 bytes, checksum: c6a71c710232c75de12d4a4e8e09a654 (MD5)Made available in DSpace on 2020-05-15T23:50:59Z (GMT). No. of bitstreams: 1 Tese_Flavia.pdf: 1036514 bytes, checksum: c6a71c710232c75de12d4a4e8e09a654 (MD5) Previous issue date: 2011-12-01Conselho Nacional de Pesquisa e Desenvolvimento Cient?fico e Tecnol?gico - CNPqapplication/pdfporUniversidade Estadual de Feira de SantanaDoutorado Acad?mico em BiotecnologiaUEFSBrasilDEPARTAMENTO DE CI?NCIAS BIOL?GICASMAPksNF?BSinaliza??o intracelularDor p?s-operat?riaDor muscularDor cr?nicaIntracellular signalingPostoperative painMuscle painChronic painCIENCIAS BIOLOGICAS::FARMACOLOGIAEnvolvimento das prote?nas quinases ativadas por mit?geno e do fator de transcri??o nuclear Kappa B em modelos experimentais de dor muscular inflamat?ria e p?s-operat?riainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesis-681526922978979154360060060060050261233834505892827008146506511543631802873727776104890info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UEFSinstname:Universidade Estadual de Feira de Santana (UEFS)instacron:UEFSORIGINALTese_Flavia.pdfTese_Flavia.pdfapplication/pdf1036514http://tede2.uefs.br:8080/bitstream/tede/1131/2/Tese_Flavia.pdfc6a71c710232c75de12d4a4e8e09a654MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82089http://tede2.uefs.br:8080/bitstream/tede/1131/1/license.txt7b5ba3d2445355f386edab96125d42b7MD51tede/11312020-05-15 20:50:59.54oai:tede2.uefs.br:8080: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Biblioteca Digital de Teses e Dissertaçõeshttp://tede2.uefs.br:8080/PUBhttp://tede2.uefs.br:8080/oai/requestbcuefs@uefs.br|| bcref@uefs.br||bcuefs@uefs.bropendoar:2020-05-15T23:50:59Biblioteca Digital de Teses e Dissertações da UEFS - Universidade Estadual de Feira de Santana (UEFS)false |
dc.title.por.fl_str_mv |
Envolvimento das prote?nas quinases ativadas por mit?geno e do fator de transcri??o nuclear Kappa B em modelos experimentais de dor muscular inflamat?ria e p?s-operat?ria |
title |
Envolvimento das prote?nas quinases ativadas por mit?geno e do fator de transcri??o nuclear Kappa B em modelos experimentais de dor muscular inflamat?ria e p?s-operat?ria |
spellingShingle |
Envolvimento das prote?nas quinases ativadas por mit?geno e do fator de transcri??o nuclear Kappa B em modelos experimentais de dor muscular inflamat?ria e p?s-operat?ria Lima, Fl?via Oliveira de MAPks NF?B Sinaliza??o intracelular Dor p?s-operat?ria Dor muscular Dor cr?nica Intracellular signaling Postoperative pain Muscle pain Chronic pain CIENCIAS BIOLOGICAS::FARMACOLOGIA |
title_short |
Envolvimento das prote?nas quinases ativadas por mit?geno e do fator de transcri??o nuclear Kappa B em modelos experimentais de dor muscular inflamat?ria e p?s-operat?ria |
title_full |
Envolvimento das prote?nas quinases ativadas por mit?geno e do fator de transcri??o nuclear Kappa B em modelos experimentais de dor muscular inflamat?ria e p?s-operat?ria |
title_fullStr |
Envolvimento das prote?nas quinases ativadas por mit?geno e do fator de transcri??o nuclear Kappa B em modelos experimentais de dor muscular inflamat?ria e p?s-operat?ria |
title_full_unstemmed |
Envolvimento das prote?nas quinases ativadas por mit?geno e do fator de transcri??o nuclear Kappa B em modelos experimentais de dor muscular inflamat?ria e p?s-operat?ria |
title_sort |
Envolvimento das prote?nas quinases ativadas por mit?geno e do fator de transcri??o nuclear Kappa B em modelos experimentais de dor muscular inflamat?ria e p?s-operat?ria |
author |
Lima, Fl?via Oliveira de |
author_facet |
Lima, Fl?via Oliveira de |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Villarreal, Cristiane Flora |
dc.contributor.advisor1ID.fl_str_mv |
89580362653 |
dc.contributor.authorID.fl_str_mv |
82466815591 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/8965167326304855 |
dc.contributor.author.fl_str_mv |
Lima, Fl?via Oliveira de |
contributor_str_mv |
Villarreal, Cristiane Flora |
dc.subject.por.fl_str_mv |
MAPks NF?B Sinaliza??o intracelular Dor p?s-operat?ria Dor muscular Dor cr?nica |
topic |
MAPks NF?B Sinaliza??o intracelular Dor p?s-operat?ria Dor muscular Dor cr?nica Intracellular signaling Postoperative pain Muscle pain Chronic pain CIENCIAS BIOLOGICAS::FARMACOLOGIA |
dc.subject.eng.fl_str_mv |
Intracellular signaling Postoperative pain Muscle pain Chronic pain |
dc.subject.cnpq.fl_str_mv |
CIENCIAS BIOLOGICAS::FARMACOLOGIA |
description |
Chronic pain is often associated with transcriptional and functional changes in neural systems involved in the transmission and modulation of nociceptive information. The transcription of several proteins involved in chronic pain is regulated by the transcription factor ?B (NF?B). Furthermore, NF?B is an important target of MAPKs (Mitogen-Activated Protein Kinase). Therefore, it was investigated the involvement of MAPKs (p38, ERK and JNK) and NF?B in two experimental models of persistent pain: inflammatory muscle pain and postoperative pain models. Pre-treatment with inhibitors of NF?B and MAPKs (p38, ERK and JNK) reduced the acute muscle hypernociception, but not persistent hypernociception. In addition, pharmacological inhibition of NF?B or p38 MAPK but not ERK and JNK, reduced postoperative hypernociception. To investigate the mechanisms by which NF?B contributes to postoperative hypernociception, we analyzed the effect of PDTC, an NF?B inhibitor, on the production of inflammatory mediators and expression of sodium channels involved in nociceptive sensitization. The incision elevated the levels of TNF-? and PGE2 as well as increased the expression of sodium channels Nav 1.8 and 1.9 in sensory neurons, these effects being were neutralized by PDTC. These data suggest that the surgical incision activates the p38 MAPK/NF?B pathway, which increases the expression of TNF-? and PGE2, responsible for the up regulation of sodium channels Nav 1.8 and Nav 1.9 in sensory neuron resulting in neuronal hyperexcitability and postoperative hypernociception. These results provide new evidence on the distinct roles of NF?B and MAPKs in the development of acute and persistent pain, and indicate that NF?B may be an interesting pharmacological target for the treatment of postoperative pain. |
publishDate |
2011 |
dc.date.issued.fl_str_mv |
2011-12-01 |
dc.date.accessioned.fl_str_mv |
2020-05-15T23:50:59Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/doctoralThesis |
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doctoralThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
LIMA, Fl?via Oliveira de. Envolvimento das prote?nas quinases ativadas por mit?geno e do fator de transcri??o nuclear Kappa B em modelos experimentais de dor muscular inflamat?ria e p?s-operat?ria. 2011. 119 f. Tese (Doutorado Acad?mico em Biotecnologia)- Universidade Estadual de Feira de Santana, Feira de Santana, 2011. |
dc.identifier.uri.fl_str_mv |
http://tede2.uefs.br:8080/handle/tede/1131 |
identifier_str_mv |
LIMA, Fl?via Oliveira de. Envolvimento das prote?nas quinases ativadas por mit?geno e do fator de transcri??o nuclear Kappa B em modelos experimentais de dor muscular inflamat?ria e p?s-operat?ria. 2011. 119 f. Tese (Doutorado Acad?mico em Biotecnologia)- Universidade Estadual de Feira de Santana, Feira de Santana, 2011. |
url |
http://tede2.uefs.br:8080/handle/tede/1131 |
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por |
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por |
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info:eu-repo/semantics/openAccess |
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openAccess |
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Universidade Estadual de Feira de Santana |
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UEFS |
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DEPARTAMENTO DE CI?NCIAS BIOL?GICAS |
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Universidade Estadual de Feira de Santana |
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