Wei Shipeng, Li Yuanyuan, Yang Ruihan, Wang Jing, Huang Fang, Fan Wenguo
Department of Anesthesiology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, No. 56 Lingyuanxi Road, Guangzhou, 510080, China.
Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China.
Med Oncol. 2025 Jul 15;42(8):334. doi: 10.1007/s12032-025-02911-1.
The sympathetic nervous system (SNS), as an important component of the peripheral nervous system, has emerged as a crucial regulator of solid tumors, from carcinogenesis to progression, metastasis, and pain. This review brings together emerging evidence that SNS signaling is involved in head and neck squamous cell carcinoma (HNSCC) progression, metastasis, and cancer-associated pain. Possible cellular and molecular mechanisms regarding the involvement are also discussed. A systematic literature search was conducted in the PubMed database focusing on SNS, HNSCC, and pain. We found that HNSCC tissues exhibit increased sympathetic nerve innervation compared to healthy tissues. SNS activity modulates key tumor biological processes, including growth and metastasis, angiogenesis, epithelial-mesenchymal transition (EMT), immune responses and apoptosis resistance, through peripheral release of neurotransmitters (primarily noradrenaline) by sympathetic postganglionic neurons or systemic release of epinephrine (Epi) into the circulation by the adrenal medulla. Notably, SNS hyperactivity exacerbates cancer pain via neuro-immune crosstalk, inducing TNF-α, NGF, and BDNF release to sensitize nociceptors. Preclinical studies demonstrate β-blockers suppress HNSCC growth, synergize with chemotherapy/radiotherapy. Therefore, understanding SNS effects on HNSCC biology can offer novel therapeutic targets for this malignancy.
交感神经系统（SNS）作为外周神经系统的重要组成部分，已成为实体瘤从致癌作用到进展、转移和疼痛的关键调节因子。本综述汇集了新出现的证据，表明SNS信号传导参与头颈部鳞状细胞癌（HNSCC）的进展、转移和癌症相关疼痛。还讨论了有关其参与的可能细胞和分子机制。在PubMed数据库中进行了系统的文献检索，重点关注SNS、HNSCC和疼痛。我们发现，与健康组织相比，HNSCC组织的交感神经支配增加。SNS活性通过交感神经节后神经元外周释放神经递质（主要是去甲肾上腺素）或肾上腺髓质将肾上腺素（Epi）全身释放到循环中，调节关键的肿瘤生物学过程，包括生长和转移、血管生成、上皮-间质转化（EMT）、免疫反应和抗凋亡。值得注意的是，SNS功能亢进通过神经-免疫串扰加剧癌症疼痛，诱导肿瘤坏死因子-α、神经生长因子和脑源性神经营养因子释放，使伤害感受器敏感化。临床前研究表明，β受体阻滞剂可抑制HNSCC生长，与化疗/放疗协同作用。因此，了解SNS对HNSCC生物学的影响可为这种恶性肿瘤提供新的治疗靶点。
