BackgroundPerturbation of neuronal excitability contributes to migraine. Neurosteroids modulate the activity of γ-aminobutyric acid A and N-methyl-d-aspartate receptors, and might be involved in the pathogenesis of migraine. Here, we measured plasma levels of four neurosteroids, i.e., allopregnanolone, epiallopregnanolone, dehydroepiandrosterone and deydroepiandrosterone sulfate, in patients affected by episodic migraine, chronic migraine, or cluster headache.MethodsNineteen female patients affected by episodic migraine, 51 female patients affected by chronic migraine, and 18 male patients affected by cluster headache were recruited to the study. Sex- and age-matched healthy control subjects (31 females and 16 males) were also recruited. Patients were clinically characterized by using validated questionnaires. Plasma neurosteroid levels were measured by liquid chromatography-tandem mass spectrometry.ResultsWe found disease-specific changes in neurosteroid levels in our study groups. For example, allopregnanolone levels were significantly increased in episodic migraine and chronic migraine patients than in control subjects, whereas they were reduced in patients affected by cluster headache. Dehydroepiandrosterone and dehydroepiandrosterone sulfate levels were reduced in patients affected by chronic migraine, but did not change in patients affected by cluster headache.ConclusionWe have shown for the first time that large and disease-specific changes in circulating neurosteroid levels are associated with chronic headache disorders, raising the interesting possibility that fluctuations of neurosteroids at their site of action might shape the natural course of migraine and cluster headache. Whether the observed changes in neurosteroids are genetically determined or rather result from exposure to environmental or intrinsic stressors is unknown. This might also be matter for further investigation because stress is a known triggering factor for headache attacks in both migraineurs and cluster headache patients.

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偏头痛和丛集性头痛显示神经类固醇模式受损

背景神经元兴奋性的扰动导致偏头痛。神经类固醇调节γ-氨基丁酸A 和N-甲基-d-天冬氨酸受体的活性，并可能参与偏头痛的发病机制。在这里，我们测量了受发作性偏头痛、慢性偏头痛或丛集性头痛影响的患者中四种神经类固醇的血浆水平，即别孕酮、表皮孕酮、脱氢表雄酮和硫酸脱氢表雄酮。 方法 19 名受发作性偏头痛影响的女性患者，51 名受慢性偏头痛影响的女性患者和 18 名受丛集性头痛影响的男性患者被招募到研究中。还招募了性别和年龄匹配的健康对照受试者（31 名女性和 16 名男性）。通过使用经过验证的问卷对患者进行临床表征。通过液相色谱-串联质谱法测量血浆神经类固醇水平。结果我们在我们的研究组中发现了神经类固醇水平的疾病特异性变化。例如，与对照组相比，发作性偏头痛和慢性偏头痛患者的别孕酮水平显着升高，而受丛集性头痛影响的患者则降低。慢性偏头痛患者的脱氢表雄酮和硫酸脱氢表雄酮水平降低，但丛集性头痛患者的脱氢表雄酮和硫酸脱氢表雄酮水平没有变化。结论我们首次表明循环神经类固醇水平的大的疾病特异性变化与慢性头痛有关，提出了一个有趣的可能性，即神经类固醇在其作用部位的波动可能会影响偏头痛和丛集性头痛的自然病程。观察到的神经类固醇的变化是由基因决定的，还是由暴露于环境或内在压力源引起的，尚不清楚。这也可能需要进一步调查，因为压力是偏头痛和丛集性头痛患者头痛发作的已知触发因素。