• Angela Koverech, Claudia Cicione, Luana Lionetto, Marta Maestri, Francesco Passariello, Elisabetta Sabbatini, Matilde Capi, Cristiano Maria De Marco, Martina Guglielmetti, Andrea Negro, Luisa Di Menna, Maurizio Simmaco, Ferdinando Nicoletti, and Paolo Martelletti.
• Department of Clinical and Molecular Medicine, Sapienza University and Regional Referral Headache Centre, Sant'Andrea Hospital, via di Grottarossa 1035-1039, 00189, Rome, Italy.
• J Headache Pain. 2019 May 27; 20 (1): 61.

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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