Zhai Qingling, Li Hongyan, Chen Qihui, Zhang Ning, Huang Yanan, Pan Yonghui
First Clinical Medical College, Harbin Medical University, Harbin, Heilongjiang, China.
Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Cephalalgia. 2025 Aug;45(8):3331024251364753. doi: 10.1177/03331024251364753. Epub 2025 Aug 26.
BackgroundNeuroinflammation, which is mediated by microglial activation, contributes to central sensitization, a key mechanism in vestibular migraine (VM). Transient receptor potential vanilloid 2 (TRPV2)-mediated calcium influx enhances nucleotide-binding oligomerization domain; leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome assembly, potentially driving inflammation. This study investigated the role of TRPV2 in VM pathogenesis.MethodsA VM model was established via repeated intraperitoneal injections of nitroglycerin and kainic acid-induced vestibular nerve terminal impairment. Periorbital thresholds and vestibular scores were measured to assess allodynia and vestibular dysfunction. Western blotting and immunofluorescence were used to evaluate TRPV2, ionized calcium-binding adapter molecule 1 (IBA1), interleukin-1β and NLRP3 expression in the spinal trigeminal nucleus caudalis (Sp5c) region. , BV2 cells treated with lipopolysaccharide and interferon-γ were transfected with TRPV2 small interfering RNA. TRPV2 activity was analyzed via patch-clamp electrophysiology. Microglial polarization and morphology were examined via flow cytometry and immunofluorescence, with a focus on CD16, CD63, CD206 and CD163 markers. NLRP3 inflammasome activation was assessed through western blotting and immunofluorescence.ResultsVM-related behaviors, including allodynia and dizziness, were successfully reproduced. Central sensitization in the Sp5c was marked by increased TRPV2 expression in microglia, as demonstrated by co-localization with the microglial marker IBA1. , TRPV2 inhibition in BV2 cells shifted microglial polarization from the pro-inflammatory M1 state to the anti-inflammatory M2 state. Additionally, TRPV2 blockade significantly reduced NLRP3 inflammasome activation and the levels of proinflammatory cytokines.ConclusionsTRPV2 regulates microglial activation and NLRP3 inflammasome activity via polarization mechanisms, contributing to central sensitization in VM. These findings highlight the critical role of TRPV2 in VM pathogenesis and its potential as a therapeutic target.
背景
由小胶质细胞激活介导的神经炎症促成了中枢敏化，这是前庭性偏头痛（VM）的关键机制。瞬时受体电位香草酸受体2（TRPV2）介导的钙内流增强了核苷酸结合寡聚化结构域；富含亮氨酸重复序列和含吡啉结构域的蛋白3（NLRP3）炎性小体组装，可能驱动炎症。本研究调查了TRPV2在VM发病机制中的作用。
方法
通过反复腹腔注射硝酸甘油和 kainic 酸诱导前庭神经末梢损伤建立VM模型。测量眶周阈值和前庭评分以评估异常性疼痛和前庭功能障碍。采用蛋白质免疫印迹法和免疫荧光法评估三叉神经脊束核尾侧亚核（Sp5c）区域中TRPV2、离子化钙结合衔接分子1（IBA1）、白细胞介素-1β和NLRP3的表达。用TRPV2小干扰RNA转染经脂多糖和干扰素-γ处理的BV2细胞。通过膜片钳电生理学分析TRPV2活性。通过流式细胞术和免疫荧光检查小胶质细胞极化和形态，重点关注CD16、CD63、CD206和CD163标志物。通过蛋白质免疫印迹法和免疫荧光评估NLRP3炎性小体激活。
结果
成功重现了与VM相关的行为，包括异常性疼痛和头晕。Sp5c中的中枢敏化表现为小胶质细胞中TRPV2表达增加，这通过与小胶质细胞标志物IBA1共定位得到证实。BV2细胞中的TRPV2抑制使小胶质细胞极化从促炎M1状态转变为抗炎M2状态。此外，TRPV2阻断显著降低了NLRP3炎性小体激活和促炎细胞因子水平。
结论
TRPV2通过极化机制调节小胶质细胞激活和NLRP3炎性小体活性，促成VM中的中枢敏化。这些发现突出了TRPV2在VM发病机制中的关键作用及其作为治疗靶点的潜力。
