The Therapeutic Potential of Melatonin in Migraines and other Headache Types

Alternative Medicine Review, August, 2001 by Joel J. Gagnier

The Pineal Gland, Melatonin, and the Migraine Connection

The pineal gland is considered a photoneuroendocrine transducer that translates environmental information into neuroendocrine molecules.[3,30-31] Brun et al[30] explain that melatonin, an indole compound, is the net result of this transduction. Melatonin is synthesized from serotonin via the enzyme Nacetyltransferase, which is emitted in a circadian cycle from the suprachiasmatic nucleus.[30] Also, the suprachiasmatic nucleus receives photic stimuli via the retinohypothalamic tract.[30] Of interest is Jacobsen's description of an oculocephalic sympathetic abnormality associated with migraine sufferers, the neural pathway of which regulates the secretion of melatonin by the pineal gland.[31]

Biochemical Studies of Melatonin and Migraines

A study to examine melatonin levels in migraine sufferers utilized 93 patients with headaches (75 women and 18 men; 38 with common migraine, 12 with ophthalmic migraine, 24 with either of the latter together with tension headache, and 19 with superimposed depression) and a control group consisting of 46 subjects (22 male and 24 female).[33] Groups were matched for sex and age and told to maintain the same light synchronization for two weeks before the study (lights off between 11 p.m. and 7 a.m.). Blood samples were drawn under low light at 11 p.m. and plasma melatonin measured in both groups. The entire migraine group had lower noctumal plasma melatonin levels than the control group (p[is less than]0.001). More specifically, migraine sufferers without depression had lower nocturnal plasma melatonin levels than controls (p [is less than] 0.01), and migraine patients with superimposed depression (p [is less than] 0.001) exhibited the greatest deficiency of melatonin compared to the control group. Interestingly, this study found only females had significantly lower levels of nocturnal melatonin excretion (female patients: 0.29 [ or -] 0.05 nmol/hr; male patients: 0.48 nmol/hr; p [is less than] 0.02). The authors explain the lack of significance in the male group to be a result of the smaller sample size and conclude, "the abnormal melatonin level we report here could reflect a global sympathetic hypofunction -- which has been demonstrated by hemodynamic and pharmacological tests in migraine- and/or a chronobiological abnormality." In light of this information the authors note melatonin could potentially act as a biochemical marker for migraine.

In another study, Brun and colleagues collected urine samples (between 7 p.m. and 7 a.m.) throughout an entire menstrual cycle, and measured melatonin levels in 10 female patients suffering menstrually associated migraines without aura. Controls consisted of nine females matched for age, body surface area, length of cycle, and fertility.[30] Compared to controls, the migraine patients had lower mean noctumal melatonin throughout the entire menstrual cycle with no differences between luteal and follicular phases, whereas controls displayed only lower follicular phase melatonin. No correlation was found between time of headache or intensity of pain and nocturnal melatonin excretion. The highest levels of melatonin in migraine patients were during menses; the authors note this could reflect rhythmic changes due to pain and/or dyssomnia. However, since lower levels of melatonin were noted outside attacks, the authors speculated that decreases of melatonin might serve as a marker of impending migraine. The authors conclude that the abnormality of melatonin secretion in migraine patients over the entire cycle could be a sympathetic hypofunction and represent a "vulnerability of the rhythmic organization of the central nervous system."