Abstract

Migraine is a common and disabling primary headache disorder and inflammation is a proposed factor in the complex ethiology of the disease. Gasdermin D (GSDMD) is a membrane pore-forming protein acting through the caspase system. End result is cell death caused by leakage of intracellular components to extracellular space which also results in inflammation. Stemming from this knowledge, the potential role of GSDMD in migraine was investigated in this prospective study. This prospective study was conducted between September 2022 to April 2023. 47 patients with migraine were designated as the patient group, whereas 47 healthy volunteers were designated as the control group. Serum GSDMD levels of both groups were compared, with an additional comparison between migraine patients during symptom-free and attack periods. Migraine related characteristics of the patients were also included in the study. Median GSDMD levels of the patient and control group did not reveal a significant difference. Nausea, vomiting and severity of headache were found to be correlated with GSDMD levels in migraine patients. Patients with nausea revealed a higher GSDMD level compared to patients without nausea during both symptom-free and attack periods (p = 0.021 and p = 0.01, respectively). Nausea was correlated to higher GSDMD levels in the patient population during symptom-free period (p = 0.030). The severity of pain was positively correlated with GSDMD levels during the attack period (p < 0.001). Gasdermin family and GSDMD in particular are promising prospects for therapy in a wide spectrum of disorders. Gasdermin proteins are candidates to be the focus for future studies both related to pathogenesis and drug therapy in migraine and varying inflammatory-driven clinical pictures.

中文翻译：

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偏头痛和gasdermin D：偏头痛炎症基础的新视角

摘要

偏头痛是一种常见且致残的原发性头痛疾病，炎症是该疾病复杂病因学中的一个被提议的因素。 Gasdermin D (GSDMD) 是一种通过 caspase 系统发挥作用的膜成孔蛋白。最终结果是细胞内成分渗漏到细胞外空间引起的细胞死亡，这也会导致炎症。基于这些知识，本前瞻性研究调查了 GSDMD 在偏头痛中的潜在作用。这项前瞻性研究于2022年9月至2023年4月期间进行。47名偏头痛患者被指定为患者组，而47名健康志愿者被指定为对照组。比较两组的血清 GSDMD 水平，并进一步比较偏头痛患者无症状期和发作期的情况。该研究还包括患者的偏头痛相关特征。患者和对照组的中位 GSDMD 水平没有显示出显着差异。研究发现恶心、呕吐和头痛的严重程度与偏头痛患者的 GSDMD 水平相关。在无症状期和发作期，恶心患者的 GSDMD 水平均高于无恶心患者（分别为p  = 0.021 和p  = 0.01）。在无症状期间，恶心与患者群体中较高的 GSDMD 水平相关（p  = 0.030）。疼痛的严重程度与发作期间的 GSDMD 水平呈正相关 ( p  < 0.001)。 Gasdermin 家族和 GSDMD 在治疗多种疾病方面尤其具有广阔的前景。 Gasdermin 蛋白是未来研究重点的候选者，这些研究涉及偏头痛的发病机制和药物治疗以及各种炎症驱动的临床情况。