Department of Clinical and Molecular Medicine, Sapienza University and Regional Referral Headache Centre, Sant'Andrea Hospital, via di Grottarossa 1035-1039, 00189, Rome, Italy.
Residency Program of Internal Medicine, School of Medicine and Psychology, Sapienza University, 00189, Rome, Italy.
J Headache Pain. 2019 May 27;20(1):61. doi: 10.1186/s10194-019-1005-0.
Perturbation 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.
Nineteen 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.
We 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.
We 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.
神经元兴奋性的紊乱与偏头痛有关。神经甾体调节γ-氨基丁酸 A 和 N-甲基-D-天冬氨酸受体的活性，可能参与偏头痛的发病机制。在此，我们测量了发作性偏头痛、慢性偏头痛和丛集性头痛患者的血浆中 4 种神经甾体的水平，即别孕烯醇酮、表孕烯醇酮、脱氢表雄酮和硫酸脱氢表雄酮。
我们招募了 19 名女性发作性偏头痛患者、51 名女性慢性偏头痛患者和 18 名男性丛集性头痛患者，同时还招募了年龄和性别匹配的健康对照组（31 名女性和 16 名男性）。患者通过验证的问卷进行临床特征描述。通过液相色谱-串联质谱法测量血浆神经甾体水平。
我们在研究组中发现了神经甾体水平的疾病特异性变化。例如，别孕烯醇酮水平在发作性偏头痛和慢性偏头痛患者中显著高于对照组，而在丛集性头痛患者中降低。脱氢表雄酮和硫酸脱氢表雄酮水平在慢性偏头痛患者中降低，但在丛集性头痛患者中没有变化。
我们首次表明，循环神经甾体水平的大幅且疾病特异性的变化与慢性头痛障碍有关，这提出了一个有趣的可能性，即神经甾体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。观察到的神经甾体变化是由遗传决定的，还是由暴露于环境或内在应激源引起的，目前尚不清楚。这也可能是进一步研究的课题，因为在偏头痛患者和丛集性头痛患者中，压力是已知的头痛发作触发因素。
