The earliest accounts of headache in Mesopotamian and Egyptian mythological texts describe magical scenes with dramatic images of suffering:

Headache roameth over the desert, blowing like the wind,

Flashing like lightning, it is loosed above and below;

It cutteth off him who feareth not his god like a reed, like a stalk of henna it slitteth his thews.

It wasteth the flesh of him who hath no protecting goddess,

Flashing like a heavenly star, it cometh like the dew;

It standeth hostile against the wayfarer, scorching him like the day,

This man it hath struck and

Like one with heart disease he staggereth,

Like one bereft of reason he is broken,

Like that which hath been cast in the fire he is shrivelled,

Like a wild ass… his eyes are full of cloud …

These Sumerian verses were translated into Assyrio-Babylonian for Ashurbanipal’s library at Niniveh in the 7th century BC (23). The clay tablets describe severe diseases as headache, but such symptoms as “flashing like a star” and “eyes full of cloud” may appear in any severe fever. In ancient Mesopotamia, malaria or septic diseases were likely causes of such symptoms. Headache was believed to be provoked by demons, and treated by incantations and strange materials fastened on the head. Some Egyptian descriptions are more specific; there one-sided headache is impressive, especially when the gods Horus and Seth are complaining about their headaches, or when Horus invokes the goddesses Isis and Nephthys, begging them to lower a spare head on him from the sky because he cannot stand his unilateral headache any longer (2).

Prehistorical trepanned skulls found in Egypt are said to have undergone brain surgery for headache. However, there is no evidence to support this claim although scraping the forehead down to the bone was a popular headache remedy among the Fellahin up to the 20th century.

Ancient Greek descriptions range from mythological scenes through clinical groundwork to philosophical critique of medical attitudes.

The Greeks knew headache as a serious complaint. Their Hippocratic corpus presents it as a frequent symptom of dangerous disease with fever, nausea, vomiting, bleeding from the nose, convulsions, and sensory disturbances (25). Zeus, the supreme god, complained of insupportable headache for which he forced Vulcan to split his head with an axe, thus giving birth to Pallas Athene, goddess of learning and strategy (4). Plato’s dialogue “Charmides” has Socrates promise a headache drug to the hero provided he first undergoes Socrates’ psychotherapy: for you cannot treat the eyes without curing the head, or the head without treating the body, nor the body without treating the soul (19).

In 1st century Rome, Aretaios of Cappadocia wrote a textbook of neurologic diseases including headache, epilepsy, and hysteria (1). He set the pattern for such textbooks up to the 19th century, and divided the headaches into heterocrania (migraine), cephalalgia (mild, infrequent headache), and cephalea (frequent, severe headache). This early classification survived with the underlying textbook structure. It provided the roots of the 1988 and 2003 international classifications of the International Headache Society, where distinction of migraine from tension-type headache (cephalalgia, cephalea) is still most important (3,5). In 2nd-century Rome, Galen of Pergamon established the master pattern of what was to become Islamic and European medicine up to the 17th century. He elaborated on Aretaios’ clinical descriptions and pathophysiology (18): migraine is caused by yellow bile irritating the brain and meninges, but the bile, held back by the falx cerebri, affects only one half of the head. Throbbing pain originates from blood vessels, and tension pain from tendons or nerves. Migraine came to us from Galen’s hemicrania through France where the physician Rabelais also used migraine for a fire grenade (12). Galen’s idea of bile from the liver causing migraine is still popular in France where migraine hépatique is attributed to liver disease. Another principal idea lasted up to the middle ages: Aretaios and Galen described Greek scotoma, Latin vertigo: vestibular vertigo with oscillopsia. This was something migraine could turn into, much more dangerous than migraine itself. Nowadays the scotoma of the ancients may be misunderstood as visual aura of migraine because this has also been called scotoma (literally, “shadow-eye”) in the last three centuries.

When Islamic medicine attempted a synthesis of Galenic medicine with Aristotelian natural science, the earlier Greek understanding of headache as a functional disorder returned. The Greek medical heritage remained alive in the Byzantine empire and the Islamic countries. In the 6th century, Alexander of Tralleis in Byzantium gave a detailed account of the headaches based on Aretaios and Galen, and on his own practical experience (21). In the 10th century the Persian physician Avicenna integrated Alexander’s concepts in his Greek-based medicine. Avicenna observed that many headaches were not caused by brain damage; the senses were not dulled but unusually acute in that any sound, light, or smell could trigger a headache (22). He established a pathogenetic classification of soda (Arabic from Persian sar dard, or headache). This system was condensed as a table in 11th century Baghdad, and became popular in Europe where it was finally printed, in Latin and German, in the 16th century (11; Table 1-1 and Fig. 1-1), demonstrating the popularity of Arabic teachings in Europe at a time when the final eviction of Islamic medicine from Europe was proposed by Paracelsus.

European medieval teachings incorporated Islamic concepts, combining the more mystical ideas of various headache Saints with clinical impressions such as Hildegard von Bingen’s finding of the comorbidity of migraine and melancholy (13), and the experimental natural science of Albert the Great and his fellow scientists of the 13th century. Hildegard had mystical visions, which have been interpreted as visual aura of migraine: the ornamental frames of her illustrations are suggestive of the zigzag contours of migraine auras. But the content of her visions is far too meaningful, and similar zigzag frames are common in illuminated books of the time. Hildegard was a compassionate clinical observer who found an original explanation for the unilaterality of migraine: nobody could survive this cruel pain if it were on both sides of the head.

In 15th- and 16th-century Galenic medicine (6), pulsatile and tension-like pain are clearly attributed to blood vessels and nerves, respectively. This ancient pathophysiology is still extant in current classification criteria: throbbing pain in migraine, tension-like pain in tension-type headache (3). The clear and orderly Galenic textbooks of this period (e.g., Houllier and Fernel [6]) set the stage for the new medicine of the scientific revolution in the 17th century where authors like Harvey and Willis integrated their new findings in a similar order.