Article
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
Registro en:
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
Autor
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
Resumen
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. 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.