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

dc.creatorLima, Flávia Oliveira de
dc.creatorLauria, Pedro Santana Sales
dc.creatorEspírito-Santo, Renan Fernandes do
dc.creatorEvangelista, Afrânio Ferreira
dc.creatorNogueira, Tâmara Magalhães Oliveira
dc.creatorAraldi, Dionéia
dc.creatorSoares, Milena Botelho Pereira
dc.creatorVillarreal, Cristiane Flora
dc.date2023-02-07T14:24:51Z
dc.date2023-02-07T14:24:51Z
dc.date2022
dc.date.accessioned2023-09-26T23:23:30Z
dc.date.available2023-09-26T23:23:30Z
dc.identifierLIMA, 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.identifier1422-0067
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/56920
dc.identifier10.3390/ijms231911630
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8890065
dc.descriptionFundação 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.
dc.descriptionAlthough 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherMDPI
dc.rightsopen access
dc.subjectDor pós-operatória
dc.subjectp38MAPK
dc.subjectNF-κB
dc.subjectTNF-a
dc.subjectCanais de sódio controlados por voltagem
dc.subjectPostoperative pain
dc.subjectp38 MAPK
dc.subjectNF-κB
dc.subjectTNF-α
dc.subjectVoltage-gated sodium channels
dc.subjectDor pós-operatória
dc.subjectProteínas Quinases p38 Ativadas por Mitógeno
dc.subjectInibidores do Fator de Necrose Tumoral
dc.titleUnveiling 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
dc.typeArticle


Este ítem pertenece a la siguiente institución