MELATONIN IN CLUSTER HEADACHE - RATIONALE FOR USE AND POSSIBLE THERAPEUTIC POTENTIAL

Cluster headache is an excruciatingly painful, essentially unilateral headache associated with homolateral autonomic signs. It has a highly distinctive temporal pattern. The attacks occur in cluster periods las ting weeks or months that are separated by remission periods of months or years. The pathogenesis of cluster headache is still unknown, alth ough it is probable that the pain and autonomic manifestations result from the activation of the trigeminovascular system. The periodic natu re of cluster headache [i.e. typically, cluster periods begin in sprin g or autumn (fall) when there is a rapid rate of change of the quantit y of daylight, and, often, within a cluster period, the attacks recur on a daily basis with 'clockwork' regularity] suggests that activation of the trigeminovascular system could derive from the involvement of the hypothalamus, the site of the biological pacemaker. Since melatoni n production is under the control of the hypothalamic pacemaker, the r ole of melatonin in cluster headache has been investigated. A number o f studies have shown that melatonin levels are reduced during cluster periods, suggesting that the disorder is associated with a periodic dy sfunction of hypothalamic structures. In this article, some of the bio logical functions of melatonin are reviewed in light of their possible relevance to the mechanisms that cause cluster headache. These includ e the role of melatonin in the regulation of circadian rhythms and the possible implications of its effects on gamma-aminobutyric acid (GABA ) and serotonin (5-hydroxytryptamine; 5-HT) receptors, intracellular l evels of calcium ions and prostaglandin production. Preliminary clinic al data on the use of melatonin in the prophylaxis of cluster headache are discussed. In a double-blind, placebo-controlled clinical study, melatonin effectively prevented cluster headache in 50% of patients. T his finding suggests the possible utility of melatonin as a second-lin e prophylactic agent, and provides additional evidence of a periodic c entral dysfunction in this disease.