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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
Journal article   Open access   Peer reviewed

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

Flávia Oliveira de Lima, Pedro Santana Sales Lauria, Renan Fernandes do Espírito-Santo, Afrânio Ferreira Evangelista, Tâmara Magalhães Oliveira Nogueira, Dionéia Araldi, Milena Botelho Pereira Soares and Cristiane Flora Villarreal
International journal of molecular sciences, Vol.23(19), p.11630
10/01/2022
DOI: 10.3390/ijms231911630
PMID: 36232927
url
https://doi.org/10.3390/ijms231911630View
Published (Version of record) Open Access

Abstract

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 expression 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. Antagonizing 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
 Animals Cyclooxygenase 2 - genetics Cyclooxygenase 2 - metabolism Disease Models, Animal Ganglia, Spinal - metabolism Male Mice Mitogen-Activated Protein Kinase 14 - metabolism NF-kappa B - metabolism Oligodeoxyribonucleotides p38 Mitogen-Activated Protein Kinases - metabolism Pain, Postoperative - drug therapy Prostaglandins E Sodium Channels - metabolism Tumor Necrosis Factor-alpha - genetics Tumor Necrosis Factor-alpha - metabolism

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