There is now evidence that
melatonin may have a role in the
biological regulation of circadian rhythms, sleep, mood, and ageing. Altered
melatonin levels in
cluster headache and
migraine have been documented.
Melatonin mechanisms are related to
headache pathophysiology in many ways, including its anti-inflammatory effect, toxic
free radical scavenging, reduction of proinflammatory
cytokine up-regulation,
nitric oxide synthase activity and
dopamine release inhibition, membrane stabilization,
GABA and
opioid analgesia potentiation,
glutamate neurotoxicity protection, neurovascular regulation,
serotonin modulation, and the similarity of chemical structure to that of
indomethacin. Treatment of
headache disorders with
melatonin and other chronobiotic agents is promising. A double-blind, placebo-controlled trial shows
melatonin is effective in
cluster headache prevention, other studies also show benefit in other disorders.
Melatonin plays an important role in
headache disorders, offering new avenues for studying their pathophysiology and treatment.