Wu Jingxiang, Li Xin, Zhang Xiaoxuan, Wang Wei, You Xingji
Department of Anesthesiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
School of Medicine, Shanghai University, Shanghai, China.
Front Mol Neurosci. 2022 Aug 1;15:963206. doi: 10.3389/fnmol.2022.963206. eCollection 2022.
Chronic pain interferes with daily functioning and is frequently accompanied by depression. Currently, traditional clinic treatments do not produce satisfactory analgesic effects and frequently result in various adverse effects. Pathogen recognition receptors (PRRs) serve as innate cellular sensors of danger signals, sense invading microorganisms, and initiate innate and adaptive immune responses. Among them, cGAS-STING alerts on the presence of both exogenous and endogenous DNA in the cytoplasm, and this pathway has been closely linked to multiple diseases, including auto-inflammation, virus infection, and cancer. An increasing numbers of evidence suggest that cGAS-STING pathway involves in the chronic pain process; however, its role remains controversial. In this narrative review, we summarize the recent findings on the involvement of the cGAS-STING pathway in chronic pain, as well as several possible mechanisms underlying its activation. As a new area of research, this review is unique in considering the cGAS-STING pathway in sensory neurons and glial cells as a part of a broader understanding of pain, including potential mechanisms of inflammation, immunity, apoptosis, and autophagy. It will provide new insight into the treatment of pain in the future.
慢性疼痛会干扰日常功能，且常伴有抑郁。目前，传统的临床治疗无法产生令人满意的镇痛效果，还常常导致各种不良反应。病原体识别受体（PRRs）作为危险信号的先天性细胞传感器，可感知入侵的微生物，并启动先天性和适应性免疫反应。其中，cGAS-STING可对细胞质中外源和内源DNA的存在发出警报，并且该通路已与多种疾病密切相关，包括自身炎症、病毒感染和癌症。越来越多的证据表明，cGAS-STING通路参与慢性疼痛过程；然而，其作用仍存在争议。在这篇叙述性综述中，我们总结了关于cGAS-STING通路参与慢性疼痛的最新发现，以及其激活的几种可能机制。作为一个新的研究领域，本综述的独特之处在于将感觉神经元和神经胶质细胞中的cGAS-STING通路视为对疼痛更广泛理解的一部分，包括炎症、免疫、细胞凋亡和自噬的潜在机制。它将为未来的疼痛治疗提供新的见解。
