Migraine: History and Discovery

Migraine is one of the oldest disorders on record, and its very name carries its history. The Greek physician Aretaeus of Cappadocia (roughly the 1st–2nd century CE) described a one-sided, recurring headache he called heterocrania; Galen of Pergamon used the term hemicrania — Greek hemi- (“half”) plus kranion (“skull”) — for pain felt over half the head. Hemicrania passed through Latin into Old French and was worn down, over centuries, into the modern word migraine. The Hippocratic writings had already noted the shimmering visual warning and the relief that vomiting can bring; the medieval abbess Hildegard of Bingen left luminous visions that later writers (notably Oliver Sacks) interpreted as migraine aura. This page traces that long road — from ancient temples to the 1873 landmark On Megrim, through the rise and fall of the “blood-vessel” theory, to the brain-centered understanding and the modern drugs (ergotamine, the triptans, and the CGRP blockers) that define migraine care today.

Table of Contents

  1. Ancient Roots: Hippocrates, Aretaeus, and Galen
  2. The Word “Migraine”: From Hemicrania to French
  3. Medieval Visions: Hildegard of Bingen and the Aura
  4. Edward Liveing and the 1873 Landmark On Megrim
  5. The Vascular Theory: Ergot, Graham, and Wolff
  6. The Neural Turn: Cortical Spreading Depression and the Trigeminovascular System
  7. Modern Drugs: Ergotamine, Triptans, and CGRP Blockers
  8. Legacy: An Ancient Complaint, A Modern Science
  9. Research Papers and References
  10. Connections

Ancient Roots: Hippocrates, Aretaeus, and Galen

Recurring, disabling one-sided headache is described in some of the earliest surviving medical writing. The texts of the Hippocratic school (around the 5th to 4th century BCE) include an account that any modern migraine patient would recognize: a man who saw “something shining before him like a light,” usually in part of the right eye, followed by a violent pain in the temple and then the whole head and neck — a pain that eased after he vomited. In a few sentences this captures the visual aura, the spreading one-sided head pain, and the curious relief that vomiting can bring, all features still listed in today’s diagnostic criteria.

The sharpest ancient clinical portrait comes from Aretaeus of Cappadocia, a Greek physician usually placed in the 1st–2nd century CE. Aretaeus distinguished, apparently for the first time, between a chronic headache (cephalea), a shorter-lasting headache (cephalalgia), and a distinct third disorder he named heterocrania — a paroxysmal pain that settled on one side of the head, shifted its position, and came wrapped in nausea, bilious vomiting, sweating, dizziness, and an aversion to light. He wrote that during an attack “life becomes a burden,” and that sufferers shun light and feel relief in the dark — an unmistakable description of the photophobia central to migraine. His careful separation of headache types is why historians regard Aretaeus as a founding figure in the clinical history of the disorder.

A century or so later, Galen of Pergamon (roughly 129–216 CE), the most influential physician of antiquity, applied the term hemicrania to this half-the-head pain and proposed an explanation rooted in the humoral medicine of his day — he linked the attacks to the rising of irritating (often “bilious”) vapors and to the membranes and vessels of the head. Galen’s vapor theory would not survive scientific scrutiny, but his word would: hemicrania became the seed of the modern name. These ancient authors are cited here as historical primary sources rather than as modern references.

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The Word “Migraine”: From Hemicrania to French

The history of migraine is unusually legible because it is written into the word itself. The Greek hemikrania — literally “half (the) skull,” from hemi- (“half”) and kranion (“skull”) — named the disorder by its single most striking feature: pain felt over one side of the head. Aretaeus’ heterocrania (“the other half of the head”) and Galen’s hemicrania were two attempts at the same idea, and it was the Galenic form that carried forward into the Latin medical tradition as hemicrania.

From there the word was steadily eroded by centuries of speech and translation. Latin hemicrania was clipped and reshaped — passing through forms rendered as hemigranea and migranea — and entered Old French, where the leading “he-” was dropped and the word became migraigne, and ultimately the modern French and English migraine. Standard etymological references trace exactly this path: Greek hemikrania → Late Latin hemicrania → Old French migraigne → English migraine. The older English folk-form of the same word, megrim, survived for centuries and is the term Edward Liveing still used in his 1873 title.

The lineage matters for more than trivia. It means the disease we now define by neurological criteria has been recognized as a discrete entity — one-sided, recurrent, distinct from ordinary headache — for the better part of two thousand years, and that every time someone says “migraine” they are unknowingly repeating a clinical observation first written down by Greek physicians: that the pain takes half the head.

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Medieval Visions: Hildegard of Bingen and the Aura

One of the most discussed episodes in migraine’s cultural history belongs to Hildegard of Bingen (1098–1179), the German Benedictine abbess, composer, naturalist, and visionary. From childhood Hildegard experienced dazzling visions — points and showers of brilliant light, shimmering concentric and crenellated forms, zigzag fortifications, and figures that flickered and “boiled” — which she recorded in words and had illuminated in manuscripts such as the Scivias. She understood them as messages from the divine, and they became the foundation of her religious authority.

Beginning in the early twentieth century, some physicians proposed that these visions were neurological in origin. In 1917 the medical historian Charles Singer argued that Hildegard’s recurrent luminous experiences were migraine aura. The idea was later popularized by the neurologist Oliver Sacks, who in his book Migraine called her visions “indisputably migrainous” and noted that the radiating, scintillating, and fortification-like patterns in her illuminations closely match the visual aura that many migraine patients see.

This remains an interpretation, not an established fact, and it deserves to be flagged as such. Hildegard left no diagnosis — the concept did not exist in her time — and historians such as Katherine Foxhall have shown how the “migrainous Hildegard” is itself a modern retrospective diagnosis, shaped by the assumptions of the men of science who proposed it, and impossible to confirm across nine centuries. What the episode does illustrate, reliably, is something migraine clinicians take seriously today: that aura is a real, structured, reproducible visual phenomenon vivid enough to have been mistaken — or received — as a vision of heaven.

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Edward Liveing and the 1873 Landmark On Megrim

For most of recorded history migraine was described but not really theorized. That changed in 1873, when the English physician Edward Liveing (1832–1919) published On Megrim, Sick-Headache, and Some Allied Disorders: A Contribution to the Pathology of Nerve-Storms — widely regarded as the first major medical treatise devoted to migraine. Drawing on years of detailed case collection, Liveing analyzed the symptoms, triggers, family patterns, and course of the disorder with a rigor that set the template for clinical headache study.

Liveing’s central idea was strikingly modern. He proposed that migraine was fundamentally a disturbance of the nervous system — a paroxysmal discharge he memorably called a “nerve-storm” — rather than a disease of the blood, the stomach, or the humors. He saw a deep kinship between migraine and epilepsy, viewing both as episodic storms arising in the central nervous system. This was, in effect, an early neural theory of migraine, advanced decades before the laboratory tools existed to test it.

The book was influential well beyond its own time. William Gowers, one of the founders of modern clinical neurology, adopted Liveing’s neurogenic view of headache. Yet in the decades that followed, Liveing’s brain-centered insight was largely set aside in favor of a vascular, blood-vessel explanation that would dominate the twentieth century — making the later return to a neural model, in a real sense, a vindication of On Megrim.

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The Vascular Theory: Ergot, Graham, and Wolff

The dominant twentieth-century explanation of migraine was vascular — the idea that the throbbing pain came from blood vessels in and around the head dilating (widening) too far. Its roots lay partly in a drug. Ergotamine, an alkaloid of the ergot fungus, had been isolated at Sandoz by Arthur Stoll in 1918 and was first used to treat migraine attacks by Maier in Switzerland in 1925; because ergotamine constricts blood vessels and relieved attacks, it seemed to point straight at the vessels as the source of the pain.

The vascular theory found its great champion in the American physician Harold G. Wolff (1898–1962). In a celebrated 1938 experiment, John Graham and Harold Wolff showed that giving ergotamine intravenously reduced the pulsations of the temporal artery in step with the easing of the headache — apparently direct evidence that dilated, pulsating vessels caused migraine pain and that constricting them brought relief. Building on such work through the mid-twentieth century, Wolff articulated the influential model (often dated to his 1948 writings) in which an initial narrowing of vessels produced the aura and a subsequent painful widening produced the headache.

The vascular theory was elegant, testable, and clinically useful, and it ruled headache medicine for roughly fifty years. But it could never fully account for migraine’s rich neurological symptoms — the aura, the nausea, the sensitivity to light and sound and smell, the warning and recovery phases — which looked far more like a brain event than a plumbing problem. As the neurologist Peter Goadsby later put it in a much-cited 2009 commentary, the vascular account was “a great story wrecked by the facts.” The stage was set for migraine to be returned to the brain.

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The Neural Turn: Cortical Spreading Depression and the Trigeminovascular System

The decisive shift — from migraine-as-blood-vessel-disease back to migraine-as-brain-disorder — rests on two pillars, one explaining the aura and one explaining the pain. The first was discovered almost by accident. In 1944, the Brazilian physiologist Aristides Leão, working at Harvard on experimental epilepsy, observed a slow wave of suppressed electrical activity creeping across the cortex of a rabbit at about 3 to 6 millimeters per minute. He named it spreading depression — now called cortical spreading depression (CSD), or “Leão’s spreading depression” — and he himself noted its resemblance to the slow march of the migraine aura. CSD is today widely accepted as the physiological basis of aura: the same slow speed explains why a migraine’s shimmering visual disturbance expands gradually across the field of vision over many minutes, far too slowly to be a vascular spasm.

The second pillar explains the headache. Beginning in the 1980s, work led by Michael Moskowitz placed the trigeminovascular system at the center of migraine pain: the trigeminal nerve fibers that wrap the blood vessels of the meninges (the coverings of the brain), when activated, release pain-signaling neuropeptides and produce a sterile, neurogenic inflammation around those vessels. Crucially, in this model the vessels are participants in a neural process, not the prime cause. One of the key neuropeptides released is calcitonin gene-related peptide (CGRP) — a discovery that would soon transform treatment.

It is worth being precise about what changed and what did not. The vascular theory was not simply “wrong” — blood vessels really are involved, and vessel-acting drugs really do help — but it was superseded: migraine is now understood as a primary disorder of the brain and its sensory nerves, in which vascular changes are downstream consequences rather than the root cause. In a satisfying historical loop, this neural picture vindicates Edward Liveing’s “nerve-storm” of 1873, set aside for a century and now restored to the center of the science.

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Modern Drugs: Ergotamine, Triptans, and CGRP Blockers

The drug history of migraine tracks its changing theory. The first era belonged to the ergot alkaloids. After ergotamine entered migraine practice in the 1920s, dihydroergotamine (DHE) followed in 1943, and for decades these were the only specific anti-migraine drugs available. They worked — but with significant cardiovascular and other risks, and with the side effects of strong, non-selective blood-vessel constriction.

The second era was a genuine breakthrough: the triptans. At Glaxo, the pharmacologist Patrick Humphrey and colleagues reasoned that a drug selectively targeting a particular serotonin (5-HT) receptor found on cranial vessels and nerve endings might abort migraine without the broad effects of ergots. Their lead compound, sumatriptan, entered clinical trials in the 1980s and was marketed in 1991 (first in the Netherlands; in the United States in 1993). As the first highly effective, well-tolerated drug developed specifically to stop a migraine attack, it was hailed as a landmark, and the American Headache Society later judged the program the most important headache-treatment advance in fifty years. A family of related triptans followed.

The newest era targets the molecule itself. Once CGRP was identified as a central player in migraine pain, drugmakers built medicines to block it. Two classes emerged: the gepants, small molecules that block the CGRP receptor (the first, olcegepant, was shown to stop attacks in humans in 2004), and the anti-CGRP monoclonal antibodies, which neutralize CGRP or its receptor for migraine prevention. On 17 May 2018, erenumab became the first such antibody approved by the U.S. Food and Drug Administration, soon joined by galcanezumab, fremanezumab, and eptinezumab, alongside a new generation of oral gepants. For the first time, migraine had drugs designed from an accurate understanding of its biology — the practical payoff of the long journey from hemicrania to CGRP.

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Legacy: An Ancient Complaint, A Modern Science

Few diseases let you read their entire intellectual history in a single word. Migraine does: hemi-kranion, “half the skull,” observed by Greek physicians, named by Galen, worn smooth by Latin and French into the word on a modern pharmacy label. Across two thousand years the clinical picture has hardly changed — one-sided throbbing pain, visual aura, nausea, recoil from light and sound — even as the explanations beneath it have been overturned more than once.

The defining arc of that history is the move from vessels to brain. Edward Liveing’s 1873 “nerve-storm” guessed it; Harold Wolff’s mid-century vascular theory eclipsed it with an elegant, drug-supported story; and the discoveries of cortical spreading depression (Leão, 1944) and the trigeminovascular system and CGRP (from the 1980s) ultimately restored it. Migraine is now firmly a disorder of the brain and its sensory nerves — with the vasculature recast as a downstream effect, not the cause.

That shift is not merely academic; it changed lives. Understanding migraine as a brain disorder driven in part by CGRP produced, for the first time, a generation of medicines built to match the disease rather than merely squeeze its blood vessels. For a complaint as old as written medicine and as common as it is disabling, the history of migraine is a clear and encouraging case study in how patient observation, honest correction of a popular theory, and basic neuroscience eventually converge into real relief.

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Research Papers and References

The list below combines key peer-reviewed historical and scientific reviews — with real DOIs or PubMed identifiers where available — and curated PubMed topic-search links into the wider literature. Ancient and early-modern primary sources (the Hippocratic writings, Aretaeus, Galen, and Edward Liveing’s 1873 On Megrim) are named in the article as historical sources rather than as modern citations. Each link opens at its source (PubMed / publisher) in a new tab.

  1. Koehler PJ, van de Wiel TWM. Aretaeus on migraine and headache. Journal of the History of the Neurosciences. 2001;10(3):253-261. — doi:10.1076/jhin.10.3.253.9089
  2. Foxhall K. Making Modern Migraine Medieval: Men of Science, Hildegard of Bingen and the Life of a Retrospective Diagnosis. Medical History. 2014;58(3):354-374. — doi:10.1017/mdh.2014.28 (PMID: 25045179)
  3. Maranhão-Filho P, Vincent M. Professor Aristides Leão. Much more than spreading depression. Headache. 2009;49(1):110-116. — doi:10.1111/j.1526-4610.2008.01210.x
  4. Goadsby PJ. The vascular theory of migraine—a great story wrecked by the facts. Brain. 2009;132(1):6-7. — doi:10.1093/brain/awn321
  5. Tfelt-Hansen PC, Koehler PJ. History of the use of ergotamine and dihydroergotamine in migraine from 1906 and onward. Cephalalgia. 2008;28(8):877-886. — doi:10.1111/j.1468-2982.2008.01578.x
  6. Humphrey PPA. The discovery and development of the triptans, a major therapeutic breakthrough. Headache. 2008;48(5):685-687. — doi:10.1111/j.1526-4610.2008.01097.x
  7. Tepper SJ. History and Review of anti-Calcitonin Gene-Related Peptide (CGRP) Therapies: From Translational Research to Treatment. Headache. 2018;58(Suppl 3):238-275. — doi:10.1111/head.13379
  8. Tfelt-Hansen PC, Koehler PJ. One hundred years of migraine research: major clinical and scientific observations from 1910 to 2010. Headache. 2011;51(5):752-778. — doi:10.1111/j.1526-4610.2011.01892.x
  9. Leão AAP — original discovery of cortical (spreading) depression of activity (1944) and its relation to migraine aura — PubMed: Leão cortical spreading depression and migraine aura
  10. Trigeminovascular system and the neural basis of migraine pain (Moskowitz and after) — PubMed: trigeminovascular system and migraine pathophysiology
  11. History of migraine: ancient, medieval, and early-modern descriptions — PubMed: history of migraine (hemicrania, ancient and medieval)
  12. Edward Liveing, “nerve-storms,” and the neurogenic theory of migraine — PubMed: Liveing, nerve-storms, and the history of migraine
  13. Vascular versus neural theories of migraine — the twentieth-century debate — PubMed: vascular versus neural theory of migraine
  14. Sumatriptan, the triptans, and CGRP-targeted drugs in migraine — PubMed: sumatriptan, triptans, and CGRP drugs in migraine

External Authoritative Resources

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Connections

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