Sleep and headache: the biological basis.

Sleep and trigeminal pain processing share several common pathways with respect to neurotransmission and functions of distinct brain areas. In this review, the role of the most important brain stem and midbrain regions for this link is discussed. The central structure involved in both headache and sleep is the hypothalamus in which the orexinergic neurons originate. These neurons project to the periaqueductal grey and are probably the anatomic and physiological link between headache and sleep. Another relevant system for this interrelationship is the melatonin metabolism. However, basic research in this field is still very preliminary and a holistic hypothesis on how sleep physiology impacts headache and vice versa is still missing.