Cecilia Rustichelli1, Elisa Bellei2, Stefania Bergamini2, Emanuela Monari2, Flavia Lo Castro3, Carlo Baraldi4, Aldo Tomasi2, Anna Ferrari5. 1. Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy. 2. Department of Surgery, Medicine, Dentistry and Morphological Sciences with Transplant Surgery, Oncology and Regenerative Medicine Relevance, University of Modena and Reggio Emilia, Modena, Italy. 3. School of Pharmacology and Clinical Toxicology, University of Modena and Reggio Emilia, Modena, Italy. 4. Department of Biomedical, Metabolic and Neural Sciences, Unit of Medical Toxicology, Headache Centre and Drug Abuse; University of Modena and Reggio Emilia, Via del Pozzo, 71, 41124, Modena, Italy. 5. Department of Biomedical, Metabolic and Neural Sciences, Unit of Medical Toxicology, Headache Centre and Drug Abuse; University of Modena and Reggio Emilia, Via del Pozzo, 71, 41124, Modena, Italy. anna.ferrari@unimore.it.
Abstract
BACKGROUND: Neurosteroids affect the balance between neuroexcitation and neuroinhibition but have been little studied in migraine. We compared the serum levels of pregnenolone sulfate, pregnanolone and estradiol in women with menstrually-related migraine and controls and analysed if a correlation existed between the levels of the three hormones and history of migraine and age. METHODS: Thirty women (mean age ± SD: 33.5 ± 7.1) with menstrually-related migraine (MM group) and 30 aged- matched controls (mean age ± SD: 30.9 ± 7.9) participated in the exploratory study. Pregnenolone sulfate and pregnanolone serum levels were analysed by liquid chromatography-tandem mass spectrometry, while estradiol levels by enzyme-linked immunosorbent assay. RESULTS: Serum levels of pregnenolone sulfate and pregnanolone were significantly lower in the MM group than in controls (pregnenolone sulfate: P = 0.0328; pregnanolone: P = 0.0271, Student's t-test), while estradiol levels were similar. In MM group, pregnenolone sulfate serum levels were negatively correlated with history of migraine (R2 = 0.1369; P = 0.0482) and age (R2 = 0.2826, P = 0.0025) while pregnenolone sulfate levels were not age-related in the control group (R2 = 0.04436, P = 0.4337, linear regression analysis). CONCLUSION: Low levels of both pregnanolone, a positive allosteric modulator of the GABAA receptor, and pregnenolone sulfate, a positive allosteric modulator of the NMDA receptor, involved in memory and learning, could contribute either to headache pain or the cognitive dysfunctions reported in migraine patients. Overall, our results agree with the hypothesis that migraine is a disorder associated with a loss of neurohormonal integrity, thus supporting the therapeutic potential of restoring low neurosteroid levels in migraine treatment.
BACKGROUND: Neurosteroids affect the balance between neuroexcitation and neuroinhibition but have been little studied in migraine. We compared the serum levels of pregnenolone sulfate, pregnanolone and estradiol in women with menstrually-related migraine and controls and analysed if a correlation existed between the levels of the three hormones and history of migraine and age. METHODS: Thirty women (mean age ± SD: 33.5 ± 7.1) with menstrually-related migraine (MM group) and 30 aged- matched controls (mean age ± SD: 30.9 ± 7.9) participated in the exploratory study. Pregnenolone sulfate and pregnanolone serum levels were analysed by liquid chromatography-tandem mass spectrometry, while estradiol levels by enzyme-linked immunosorbent assay. RESULTS: Serum levels of pregnenolone sulfate and pregnanolone were significantly lower in the MM group than in controls (pregnenolone sulfate: P = 0.0328; pregnanolone: P = 0.0271, Student's t-test), while estradiol levels were similar. In MM group, pregnenolone sulfate serum levels were negatively correlated with history of migraine (R2 = 0.1369; P = 0.0482) and age (R2 = 0.2826, P = 0.0025) while pregnenolone sulfate levels were not age-related in the control group (R2 = 0.04436, P = 0.4337, linear regression analysis). CONCLUSION: Low levels of both pregnanolone, a positive allosteric modulator of the GABAA receptor, and pregnenolone sulfate, a positive allosteric modulator of the NMDA receptor, involved in memory and learning, could contribute either to headache pain or the cognitive dysfunctions reported in migrainepatients. Overall, our results agree with the hypothesis that migraine is a disorder associated with a loss of neurohormonal integrity, thus supporting the therapeutic potential of restoring low neurosteroid levels in migraine treatment.
Authors: Mariangela Chisari; Timothy J Wilding; Samuel Brunwasser; Kathiresan Krishnan; Mingxing Qian; Ann Benz; James E Huettner; Charles F Zorumski; Douglas F Covey; Steven Mennerick Journal: Neuropharmacology Date: 2018-10-15 Impact factor: 5.250