S100A9 plays a pivotal role in a mouse model of herpetic neuralgia via TLR4/TNF pathway.

Abstract

Herpetic neuralgia is a painful condition following herpes zoster disease, which results from Varicella-zoster virus reactivation in the dorsal or trigeminal sensory ganglia. Nevertheless, the pathophysiological mechanisms involved in herpetic neuralgia are not well understood. Recently, we identified, that neuroimmune-glia interactions in the sensory ganglion is a critical mechanism for the development of herpetic neuralgia. Here, we investigate the contribution of S100A9, a well-known pro-inflammatory molecule produced by myeloid cells, for the development of herpetic neuralgia using a murine model of HSV-1 infection. We found that cutaneous HSV-1 infection results in an increase of S100A9 expression in the Dorsal Root Ganglia (DRGs). Infiltrating neutrophils into the DRGs were the main source of S100A9 post HSV-1 infection. Functionally, genetic or pharmacological inhibition of S100A9 impairs the development of HSV-1 infection-induced mechanical pain hypersensitivity. Finally, we found that the pronociceptive role of S100A9 in herpetic neuralgia depends on the TLR4/TNF pathway. These results unraveled previously unknown mechanisms involved in the pathophysiology of herpetic neuralgia and indicate that S100A9 might be an important target for novel therapies aiming acute herpetic neuralgia.

• Authors: Cássia R Silva, Bruno M S Melo, Jaqueline R Silva, Alexandre H Lopes, Janaina A Pereira, Nerry T Cecilio, Jonilson Berlink, Giovani G Souza, Guilherme Lucas, Thomas Vogl, Fernando Q Cunha, José C Alves-Filho, Thiago M Cunha
• Journal: Brain, behavior, and immunity (Brain Behav Immun) Vol. 88 Pg. 353-362 (08 2020) ISSN: 1090-2139 [Electronic] Netherlands
• PMID: 32243898 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Calgranulin B
• S100A9 protein, mouse
• Tlr4 protein, mouse
• Toll-Like Receptor 4

Topics

• Animals
• Calgranulin B
• Disease Models, Animal
• Herpes Zoster
• Mice
• Neuralgia
• Neuroglia
• Toll-Like Receptor 4 (genetics)