Jiang Dongzhi, Zhang Ziyuan, Ren Fei, Sun Wenqin
Department of Anesthesiology, Changde Hospital, Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City), Changde, Hunan, China.
Xiangya Hospital, Central South University, Changsha, Hunan, China.
Front Immunol. 2025 Jul 4;16:1615638. doi: 10.3389/fimmu.2025.1615638. eCollection 2025.
Herpes zoster (HZ), a neurological disorder resulting from varicella-zoster virus (VZV) reactivation, presents significant clinical challenges, particularly in the development of postherpetic neuralgia (PHN). This comprehensive review elucidates the pivotal role of S100A8/A9, a damage-associated molecular pattern (DAMP) molecule, in the pathogenesis of chronic pain transition. By systematically analyzing molecular mechanisms, we provide unprecedented insights into the complex neuroimmune interactions underlying HZ-associated neuropathic pain. Our investigation reveals S100A8/A9's critical function in modulating neuroinflammatory processes through TLR4/TNF signaling pathways, demonstrating its potential as a sophisticated therapeutic target. The protein complex orchestrates intricate cellular communications, fundamentally disrupting neuronal homeostasis and contributing to pain chronification. Emerging technological platforms, including single-cell sequencing and multi-omics analysis, have substantially enhanced our understanding of these molecular dynamics. The review critically examines current therapeutic limitations and proposes innovative research directions. By integrating molecular, cellular, and clinical perspectives, we highlight the urgent need for personalized intervention strategies that address the multifaceted mechanisms of HZ-induced neuropathic pain. Our findings underscore S100A8/A9's significance as a promising biomarker and potential therapeutic intervention in neurological disorders.
带状疱疹（HZ）是由水痘-带状疱疹病毒（VZV）重新激活引起的一种神经疾病，带来了重大的临床挑战，尤其是在疱疹后神经痛（PHN）的发展方面。这篇全面综述阐明了损伤相关分子模式（DAMP）分子S100A8/A9在慢性疼痛转变发病机制中的关键作用。通过系统分析分子机制，我们对HZ相关神经性疼痛背后复杂的神经免疫相互作用有了前所未有的见解。我们的研究揭示了S100A8/A9通过TLR4/TNF信号通路调节神经炎症过程的关键功能，证明了其作为一个精密治疗靶点的潜力。该蛋白复合物精心安排复杂的细胞通讯，从根本上破坏神经元的稳态并导致疼痛慢性化。包括单细胞测序和多组学分析在内的新兴技术平台极大地增强了我们对这些分子动力学的理解。这篇综述批判性地审视了当前的治疗局限性并提出了创新的研究方向。通过整合分子、细胞和临床观点，我们强调迫切需要针对HZ诱导的神经性疼痛多方面机制的个性化干预策略。我们的研究结果强调了S100A8/A9作为一种有前景的生物标志物以及在神经疾病中潜在治疗干预的重要性。
