Migraine and cluster headache show impaired neurosteroids patterns

Abstract

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.

Serum levels of allopregnanolone, progesterone and testosterone in menstrually-related and postmenopausal migraine: A cross-sectional study

“…Recently, allopregnanolone serum levels have been found to be significantly increased in patients with episodic and chronic migraine compared to healthy controls. Since this study (31) does not specify the phase of the sampling, and not even how many women were of fertile or menopausal age and the number of males (apart from those with cluster headache), the comparison with our results is unfeasible.…”

Comparing Perimenstrual and Nonperimenstrual Migraine Attacks Using an e-Diary

“… 46 However, conflicting results were observed in small studies for serum allopregnanolone concentrations between women with and without migraine. 47 , 48 …”

Alleviation of migraine symptoms by application of repetitive peripheral magnetic stimulation to myofascial trigger points of neck and shoulder muscles – A randomized trial

“…Further, assessing the effects of a novel method like rPMS on advanced migraine markers evaluated by emerging technologies, i.e. the expression of specific neurosteroid www.nature.com/scientificreports www.nature.com/scientificreports/ patterns or facial electronic thermography, may track progress in the understanding of distinct neuromodulatory mechanisms [56][57][58][59][60] .…”