The Therapeutic Potential of Melatonin in Migraines and other Headache Types

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

Abstract

A large number of individuals suffer from migraine headaches. Several theories attempt to explain migraine etiology. One such theory holds that since environmental stimuli are well known to trigger migraine headaches, the pineal gland may be involved in migraine etiology. Specifically, a pineal gland irregularity may be the physical origin of migraine headaches, with subsequent physiological changes being secondary. Research has found the pineal hormone melatonin is low in migraine patients. Additionally, several studies found administering melatonin to migraine sufferers relieved pain and decreased headache recurrence in some cases. It has been suggested melatonin may play an important therapeutic role in the treatment of migraines and other types of headaches, particularly those related to delayed sleep phase syndrome. Current research supports the hypothesis that migraines are a response to a pineal circadian irregularity in which the administration of melatonin normalizes this circadian cycle; i.e., melatonin may play a role in resynchronizing biological rhythms to lifestyle and subsequently relieve migraines and other forms of headaches. In addition, research testing the administration of melatonin found it safe in migraine sufferers, with few or no side effects. However, a larger, randomized control trial is needed to definitively determine if administration of melatonin to migraine patients is effective.

(Altern Med Rev 2001;6(4):383-389)

Introduction

In the United States, approximately 24 million individuals suffer from migraine headaches.[1] These occur more often in women than men, between the ages of 10 and 40, and often remit after age 50. In addition, there appears to be some familial origin. A migraine headache is defined as, "a benign recurring headache and/or neurologic dysfunction usually attended by pain-free interludes and often provoked by stereotyped stimuli. A migraine may be identified both by its activators (red wine, hunger, lack of sleep, glare, perfume, periods of letdown) and its deactivators (sleep, pregnancy, exhilaration, sumatriptan.")[2] A migraine headache can last 4-72 hours, is throbbing, moderate to severe in intensity, and unilateral; becomes worse with exertion: and is associated with nausea, vomiting, and sensitivity to light, sound, and smell.[1] Subcategories include common migraine, classic migraine, basilar migraine, and carotidynia.[2]

Theories of Migraine Pathophysiology

Several theories have attempted to explain migraine etiology.[2,3] Wolff[4] and Graham[2] postulated that the aura associated with a classic migraine was due to intracerebral vasoconstriction and the headache due to reflex vasodilation. This "vascular" hypothesis was deemed valid for many years;[2] although, as Sandyk[3] pointed out, "The theory was not supported by evidence from cerebral blood flow studies."[4-7]

Sicuteri[8] postulated that a decrease in serotonin was responsible for the pain associated with a migraine and that the dilation of vessels was nonessential. This theory is supported by the alleviation of symptoms with administration of serotonin precursors, the production of symptoms with 5-hydoxytryptophan (5-HTP) synthesis inhibitors, and the alleviation of symptoms with 5-HT 1 receptor agonists such as sumatriptan.[2,9-11] Raskin[2] notes that the dorsal raphe, having the highest concentration of serotonin receptors in the brain parenchyma, may be the midbrain trigger for migraine.

In the 1940s, Lashley, Leao, and a host of other researchers thereafter, described a spreading neuronal depression across the occipital and cerebral cortex preceded by an excitatory wave-front.[2,12-15] More recent research describes a spreading wave of neuronal depression originating in the posterior cerebral regions.[16] Support for this theory abounds in cerebral blood flow (CBF), electroencephalogram (EEG), and magnetoencephalographic studies,[17-24] and suggests migraine etiology is due to a brain parenchymal disturbance leading to a spreading depolarization with vascular reactions being secondary.

Raskin outlines three mechanisms and anatomic regions that summarize the current understanding of the pathogenesis of migraine. "First, there is a vasomotor component mediated by constriction or dilation of arteries within and outside the brain. Second, there is a midbrain trigger, perhaps in serotonergic neurons of the dorsal raphe. Third, there is activation of a trigeminal vascular system, consisting of medullary neurons in the trigeminal nucleus caudalis that terminate on the walls of arteries and release neuroactive peptides."[2]

Some researchers have posited an environmental etiology since factors such as light, noise, smell, temperature, and humidity appear to contribute to migraine onset.[3] They suggest, in addition, that periodicity and seasonal fluctuations support an environmental etiology to migraine.[3,25-29] It has been hypothesized that the pineal gland is the connection between migraine headaches and environmental triggers, and that the causative neuroactive chemical is a hormone.[3,30-31]