Song Xiaoli, Zhu Qian, Zhang Jieying, Yang Jin, Zhang Xinxin, Song Qian
National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China.
First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Front Immunol. 2025 Jul 16;16:1632154. doi: 10.3389/fimmu.2025.1632154. eCollection 2025.
Migraines are among the most common neurological disorders, disabling nearly one in seven people worldwide, whereas glioblastoma (GBM) is the most aggressive primary brain tumour, with median survival scarcely beyond 15 months. Historically considered distinct, these conditions are increasingly linked by trigeminal nerve-driven neurogenic inflammation. Activation of trigeminovascular afferents provokes antidromic release of calcitonin gene-related peptide (CGRP), substance P (SP), and pituitary adenylate cyclase-activating polypeptide (PACAP); beyond mediating migraine pain, these peptides remodel vasculature, immune infiltrates, and extracellular matrix to facilitate GBM invasion. Pre-clinical studies show CGRP and SP up-regulate matrix-metalloproteinases and integrins, while PACAP modulates cAMP-MAPK signalling, collectively promoting perivascular migration and temozolomide resistance. Epidemiological analyses report higher migraine antecedents in patients later diagnosed with brain tumours, and high-resolution MRI frequently localises GBM spread along trigeminal pathways, underscoring anatomical plausibility. Emerging therapeutics mirror these insights: aprepitant (an NK1-receptor antagonist) triggers GBM apoptosis, gepant-class CGRP blockers curb invasive phenotypes, and radiolabelled SP analogues deliver focal alpha-therapy. These discoveries facilitate more precise pathogenetic characterisation, reduce diagnostic uncertainty, and expedite translational drug development. This review synthesises current evidence on trigeminal neurogenic inflammation as a mechanistic conduit between migraine biology and GBM progression, mapping cellular circuits, molecular crosstalk, and translational interventions. By integrating neurobiology, oncology, and pharmacology, we aim to delineate diagnostic blind spots, spotlight drug-repurposing opportunities, and chart a roadmap toward personalised strategies that simultaneously alleviate migraine burden and restrain glioblastoma aggressiveness.
偏头痛是最常见的神经系统疾病之一，全球近七分之一的人受其困扰，而胶质母细胞瘤（GBM）是最具侵袭性的原发性脑肿瘤，中位生存期几乎不超过15个月。这些疾病在历史上被认为是不同的，但现在越来越多地通过三叉神经驱动的神经源性炎症联系在一起。三叉神经血管传入纤维的激活会引发降钙素基因相关肽（CGRP）、P物质（SP）和垂体腺苷酸环化酶激活多肽（PACAP）的逆向释放；这些肽除了介导偏头痛疼痛外，还会重塑血管、免疫浸润和细胞外基质，以促进GBM的侵袭。临床前研究表明，CGRP和SP上调基质金属蛋白酶和整合素，而PACAP调节cAMP-MAPK信号传导，共同促进血管周围迁移和替莫唑胺耐药性。流行病学分析报告称，后来被诊断患有脑肿瘤的患者中偏头痛病史较多，高分辨率MRI经常显示GBM沿三叉神经通路扩散，这突出了解剖学上的合理性。新兴疗法反映了这些见解：阿瑞匹坦（一种NK1受体拮抗剂）可引发GBM凋亡，gepant类CGRP阻滞剂可抑制侵袭性表型，放射性标记的SP类似物可提供局部α治疗。这些发现有助于更精确地描述发病机制，减少诊断不确定性，并加速转化药物开发。本综述综合了关于三叉神经源性炎症作为偏头痛生物学和GBM进展之间机制通道的现有证据，绘制了细胞回路、分子串扰和转化干预措施。通过整合神经生物学、肿瘤学和药理学，我们旨在勾勒出诊断盲点，突出药物再利用机会，并绘制一条通向个性化策略的路线图，同时减轻偏头痛负担并抑制胶质母细胞瘤的侵袭性。
