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Messina A, Bitetti I, Precenzano F, et al. Non-Rapid Eye Movement Sleep Parasomnias and Migraine: A Role of Orexinergic Projections. Front Neurol. 2018;9:95doi: 10.3389/fneur.2018.00095.
Messina, A., Bitetti, I., Precenzano, F., Iacono, D., Messina, G., Roccella, M., Parisi, L., Salerno, M., Valenzano, A., Maltese, A., Salerno, M., Sessa, F., Albano, G. D., Marotta, R., Villano, I., Marsala, G., Zammit, C., Lavano, F., Monda, M., Cibelli, G., Lavano, S. M., Gallai, B., Toraldo, R., Monda, V., & Carotenuto, M. (2018). Non-Rapid Eye Movement Sleep Parasomnias and Migraine: A Role of Orexinergic Projections. Frontiers in neurology, 995. https://doi.org/10.3389/fneur.2018.00095
Messina, Antonietta, et al. "Non-Rapid Eye Movement Sleep Parasomnias and Migraine: A Role of Orexinergic Projections." Frontiers in neurology vol. 9 (2018): 95. doi: https://doi.org/10.3389/fneur.2018.00095
Messina A, Bitetti I, Precenzano F, Iacono D, Messina G, Roccella M, Parisi L, Salerno M, Valenzano A, Maltese A, Salerno M, Sessa F, Albano GD, Marotta R, Villano I, Marsala G, Zammit C, Lavano F, Monda M, Cibelli G, Lavano SM, Gallai B, Toraldo R, Monda V, Carotenuto M. Non-Rapid Eye Movement Sleep Parasomnias and Migraine: A Role of Orexinergic Projections. Front Neurol. 2018 Feb 28;9:95. doi: 10.3389/fneur.2018.00095. eCollection 2018. PMID: 29541053; PMCID: PMC5835506.
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Front Neurol. 2018 Feb 28;9:95. doi: 10.3389/fneur.2018.00095. eCollection 2018.

Non-Rapid Eye Movement Sleep Parasomnias and Migraine: A Role of Orexinergic Projections.

Frontiers in neurology

Antonietta Messina, Ilaria Bitetti, Francesco Precenzano, Diego Iacono, Giovanni Messina, Michele Roccella, Lucia Parisi, Margherita Salerno, Anna Valenzano, Agata Maltese, Monica Salerno, Francesco Sessa, Giuseppe Davide Albano, Rosa Marotta, Ines Villano, Gabriella Marsala, Christian Zammit, Francesco Lavano, Marcellino Monda, Giuseppe Cibelli, Serena Marianna Lavano, Beatrice Gallai, Roberto Toraldo, Vincenzo Monda, Marco Carotenuto

Affiliations

  1. Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.
  2. Clinic of Child and Adolescent Neuropsychiatry, Center for Childhood Headache, Department of Mental Health, Physical and Preventive Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.
  3. Neurodevelopmental Research Lab, Biomedical Research Institute of New Jersey (BRInj), Cedar Knolls NJ, United States.
  4. Neuroscience Research, MidAtlantic Neonatology Associates, Atlantic Health System, Morristown NJ, United States.
  5. Neuropathology Research, MidAtlantic Neonatology Associates (MANA) and Biomedical Research Institute of New Jersey (BRInj), Morristown, NJ, United States.
  6. Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
  7. Child Neuropsychiatry, Department of Psychology and Pedagogical Sciences, University of Palermo, Palermo, Italy.
  8. Department of Health Sciences, University "Magna Graecia", Catanzaro, Italy.
  9. Struttura Complessa di Farmacia, Azienda Ospedaliero-Universitaria, Ospedali Riuniti di Foggia, Foggia, Italy.
  10. Anatomy Department, Faculty of Medicine and Surgery, University of Malta, Msida, Malta.
  11. Department of Surgical and Biomedical Sciences, University of Perugia, Perugia, Italy.

PMID: 29541053 PMCID: PMC5835506 DOI: 10.3389/fneur.2018.00095

Abstract

INTRODUCTION: Sleep and migraine share a common pathophysiological substrate, although the underlying mechanisms are unknown. The serotonergic and orexinergic systems are both involved in the regulation of sleep/wake cycle, and numerous studies show that both are involved in the migraine etiopathogenesis. These two systems are anatomically and functionally interconnected. Our hypothesis is that in migraine a dysfunction of orexinergic projections on the median raphe (MR) nuclei, interfering with serotonergic regulation, may cause Non-Rapid Eye Movement parasomnias, such as somnambulism.

HYPOTHESIS/THEORY: Acting on the serotonergic neurons of the raphe nuclei, the dysfunction of orexinergic neurons would lead to a higher release of serotonin. The activation of serotonergic receptors located on the walls of large cerebral vessels would lead to abnormal vasodilatation and consequently increase transmural pressure. This process could activate the trigeminal nerve terminals that innervate vascular walls. As a consequence, there is activation of sensory nerve endings at the level of hard vessels in the meninges, with release of pro-inflammatory peptides (e.g., substance P and CGRP). Within this hypothetical frame, the released serotonin could also interact with trigeminovascular afferents to activate and/or facilitate the release of the neuropeptide at the level of the trigeminal ganglion. The dysregulation of the physiological negative feedback of serotonin on the orexinergic neurons, in turn, would contribute to an alteration of the whole system, altering the sleep-wake cycle.

CONCLUSION: Serotonergic neurons of the MR nuclei receive an excitatory input from hypothalamic orexin/hypocretin neurons and reciprocally inhibit orexin/hypocretin neurons through the serotonin 1A receptor (or 5-HT1A receptor). Considering this complex system, if there is an alteration it may facilitate the pathophysiological mechanisms involved in the migraine, while it may produce at the same time an alteration of the sleep-wake rhythm, causing sleep disorders such as sleepwalking. Understanding the complex mechanisms underlying migraine and sleep disorders and how these mechanisms can interact with each other, it would be crucial to pave the way for new therapeutic strategies.

Keywords: migraine; orexinergic system; pro-inflammatory peptides; serotonergic system; sleep–wake rhythm

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