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Role of Melatonin in the Pathophysiology of Migraine

Implications for Treatment

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Abstract

The pineal gland and its secretory product, melatonin, have been implicated in the pathophysiology of migraine, as well as some of its comorbid disorders. Supporting this view, many migraineurs are susceptible to various environmental triggers that influence the secretion of melatonin from the pineal gland, and many prodromal symptoms are probably generated in the hypothalamus, a brain region that provides input into the pineal gland to modulate the secretion of melatonin. In addition, studies have shown abnormalities in melatonin secretion in patients who experience migraine and an improvement in migraine following administration of melatonin. However, the dysfunction in melatonin secretion in migraineurs may simply be a marker of hypothalamic dysfunction or neuronal hyperexcitability, leading to migraine susceptibility. It is also possible that abnormal melatonin secretion leads to decreased inhibitory neurotransmitter activity, decreased inhibition of the release of calcitonin gene-related peptide (CGRP) from activation of the trigeminal system, or less analgesia.

Whatever its role in the pathogenesis of migraine, melatonin may prove to be a useful therapy. Future studies are necessary to further elucidate whether melatonin is a well tolerated, beneficial therapy, and to determine the optimal dose and formulation of melatonin for use in migraine therapy.

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Acknowledgements

The authors received no funding to prepare this review and have no conflicts of interest directly relevant to its content.

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Authors and Affiliations

  1. Jefferson Headache Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

    Barbara Vogler

  2. The New England Center for Headache, 778 Long Ridge Road, Stamford, Connecticut, 06902, USA

    Alan M. Rapoport, Stewart J. Tepper, Fred Sheftell & Marcelo E. Bigal

  3. Department of Neurology, Columbia University College of Physicians and Surgeons, New York, New York, USA

    Alan M. Rapoport

  4. Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, USA

    Stewart J. Tepper

  5. Department of Psychiatry, New York Medical College, Valhalla, New York, USA

    Fred Sheftell

  6. Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, USA

    Marcelo E. Bigal

Authors
  1. Barbara Vogler
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  2. Alan M. Rapoport
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  3. Stewart J. Tepper
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  4. Fred Sheftell
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  5. Marcelo E. Bigal
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Correspondence to Alan M. Rapoport.

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Vogler, B., Rapoport, A.M., Tepper, S.J. et al. Role of Melatonin in the Pathophysiology of Migraine. CNS Drugs 20, 343–350 (2006). https://doi.org/10.2165/00023210-200620050-00001

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