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.

中文翻译：

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S100A9 通过 TLR4/TNF 通路在疱疹性神经痛小鼠模型中发挥关键作用

疱疹性神经痛是带状疱疹疾病后的一种疼痛状况，它是由背侧或三叉感觉神经节中的水痘-带状疱疹病毒重新激活引起的。然而，疱疹性神经痛所涉及的病理生理机制尚不清楚。最近，我们发现，感觉神经节中的神经免疫-胶质细胞相互作用是疱疹性神经痛发展的关键机制。在这里，我们使用 HSV-1 感染的小鼠模型研究 S100A9（一种由骨髓细胞产生的众所周知的促炎分子）对疱疹性神经痛发展的贡献。我们发现皮肤 HSV-1 感染导致背根神经节 (DRG) 中 S100A9 表达增加。中性粒细胞浸润到 DRGs 是 HSV-1 感染后 S100A9 的主要来源。在功能上，S100A9 的遗传或药理学抑制会损害 HSV-1 感染诱导的机械疼痛超敏反应的发展。最后，我们发现 S100A9 在疱疹性神经痛中的促痛作用取决于 TLR4/TNF 通路。这些结果揭示了与疱疹性神经痛的病理生理学有关的先前未知的机制，并表明 S100A9 可能是针对急性疱疹性神经痛的新疗法的重要靶点。