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
Abstract
:1. Introduction
2. Results
2.1. Plantar Incision-Induced Mechanical Hypernociception Accompanies Increased Expression of Nav1.8 and Nav1.9 in the Dorsal Root Ganglia
2.2. Downregulating Nav1.8 and Nav1.9 in the Dorsal Root Ganglia Reduces Plantar Incision-Induced Hypernociception
2.3. Plantar Incision Leads to Increased Expression of the Hypernociceptive Mediators TNF-α and COX-2/PGE2 in the Dorsal Root Ganglia and in the Plantar Skin
2.4. TNF-α and Prostanoids Contribute to Hypernociception, but Only TNF-α Contributes to Upregulation of Nav1.8 and Nav1.9 in the Dorsal Root Ganglia
2.5. The p38 MAPK/NF-κB Pathway Plays a Role in the Pathophysiology of the Mouse Model of Incisional Pain
2.6. Activating the NF-κB Pathway Increases the Expression of TNF-α and COX-2/PGE2 in the Dorsal Root Ganglia and in the Plantar Skin of Incised Mice
3. Discussion
4. Materials and Methods
4.1. Animals
4.2. Mouse Model of Incisional Pain
4.3. The von Frey Test for Mechanical Nociception
4.4. Real-Time PCR
4.5. Nav1.8 and Nav1.9 Knock-Down
4.6. TNF-α Quantification by ELISA
4.7. Prostaglandin E2 Quantification
4.8. Pharmacological Assays
4.9. Statistical Analyses
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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de Lima, F.O.; Lauria, P.S.S.; do Espírito-Santo, R.F.; Evangelista, A.F.; Nogueira, T.M.O.; Araldi, D.; Soares, M.B.P.; Villarreal, C.F. 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. Int. J. Mol. Sci. 2022, 23, 11630. https://doi.org/10.3390/ijms231911630
de Lima FO, Lauria PSS, do Espírito-Santo RF, Evangelista AF, Nogueira TMO, Araldi D, Soares MBP, Villarreal CF. 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. 2022; 23(19):11630. https://doi.org/10.3390/ijms231911630
Chicago/Turabian Stylede Lima, Flávia Oliveira, 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. 2022. "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 23, no. 19: 11630. https://doi.org/10.3390/ijms231911630