Migraine: History and Discovery

Migraine is one of the oldest recorded human afflictions, and its story is woven into the history of medicine itself. The very word descends from the Greek hemicrania — “half the skull” — coined for the one-sided headache by the physicians of antiquity. Across two and a half millennia, migraine has been described by Hippocrates, classified by Aretaeus of Cappadocia, depicted (some argue) in the radiant visions of a medieval abbess, and finally dissected by modern neuroscience. This page traces that long arc, with particular attention to the great twentieth-century reversal: the slow fall of the once-dominant vascular theory and the rise of today’s neural, brain-centered understanding of migraine. Every name, date, and “first” below has been checked against multiple sources; where a claim is an interpretation rather than an established fact, it is flagged plainly as such.

Ancient Origins: The Earliest Descriptions
The Word Itself: Hemicrania to “Migraine”
The Medieval Period and Hildegard’s Visions
The 19th Century: Liveing and the Nerve-Storm
The Vascular Theory: Harold Wolff’s Era
The Neural Turn: Cortical Spreading Depression
The Trigeminovascular System and CGRP
From Ergotamine to Triptans to CGRP Blockers
Legacy: A Brain Disorder, Reclaimed
Research Papers and References
Connections

Ancient Origins: The Earliest Descriptions

Headache that comes in attacks, sits on one side of the head, and is accompanied by sickness has been recognized for as long as people have written about illness. Some of the very oldest medical texts — from ancient Mesopotamia and from Egyptian papyri — describe one-sided, throbbing “sick headaches,” though these descriptions are brief and their identification with modern migraine is necessarily approximate. What is not in doubt is that classical Greek medicine left descriptions specific enough that physicians today recognize migraine in them at once.

The earliest such account is usually credited to Hippocrates (c. 460–370 BCE) or the Hippocratic writers around 400 BCE. They recorded the case of a man who saw “something shining before him like a light, usually in part of the right eye,” after which “a violent pain supervened in the right temple, then in all the head and neck,” and which finally settled after he vomited. That single sentence captures the three hallmarks of migraine with aura: a visual disturbance, a severe one-sided headache, and relief (or at least an endpoint) with vomiting. It is one of the oldest clear descriptions of migraine aura in all of medicine.

The most influential ancient classification came from Aretaeus of Cappadocia (commonly dated to the first–second century CE), often called “the father of the migraine concept.” Aretaeus sorted headaches into three kinds: cephalalgia (a mild, passing head pain), cephalea (a chronic, severe headache, broadly comparable to what we might call tension-type headache today), and heterocrania — literally “other-half-head” — a paroxysmal, one-sided headache attended by nausea, bilious vomiting, sweating, light intolerance, and disturbances of smell. Heterocrania corresponds closely to modern migraine, and Aretaeus’s tripartite scheme was consulted for many centuries afterward.

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The Word Itself: Hemicrania to “Migraine”

The name we use today is itself a fossil of this ancient observation. The Greek term hemikrania (ἹμικρᲵνᲱᲱ) combines hemi-, “half,” with kranion, “skull” — literally “pain in half of the head.” The great physician Galen of Pergamon (c. 129–c. 216 CE) used hemicrania for the one-sided headache, and it is largely through Galen’s towering authority that the word was fixed in the medical vocabulary of the Western and Islamic worlds for the next thousand years. (The basic Greek term predates Galen, but his usage is the reason it endured.)

From there the word travelled and wore down. Greek hemikrania passed into Late Latin as hemicrania. In Old French the hard-to-pronounce opening was smoothed away — the silent or near-silent “he-” was reinterpreted as not part of the word and dropped — producing migraigne, then migraine. English borrowed the word, in a scatter of spellings, around the year 1400; older English forms such as “megrim” (the very word Edward Liveing still used in his 1873 title) are the same term in native dress. So the everyday word “migraine” carries, hidden inside it, a two-thousand-year-old clinical observation: that this headache so often takes only half the head.

The thread is therefore continuous and verifiable: Greek hemikrania → Galen’s hemicrania → Latin hemicrania → Old French migraigne / migraine → the modern English word. Few medical terms preserve their origin so transparently, and fewer still describe the same disease, in the same way, across so vast a span of time.

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The Medieval Period and Hildegard’s Visions

Through the medieval centuries, migraine was discussed within the framework inherited from Galen and the classical authors, transmitted and elaborated by physicians of the medieval Islamic world and then by the medical schools of Europe. Treatments were largely humoral — bleeding, purging, dietary regimens, and topical applications — and the one-sided “hemicrania” remained a recognized clinical entity throughout. What the medieval period also produced, more famously, is a striking and much-debated possible depiction of migraine aura.

Hildegard of Bingen (1098–1179), the German Benedictine abbess, composer, and polymath, recorded throughout her life a series of luminous religious visions — shimmering points of light, concentric and crenellated shapes, zigzag fortifications, and fields of brightness that expanded and then collapsed. She understood these as divine revelations and built much of her theological work around them. Centuries later, several writers proposed a neurological reading. The historian Charles Singer suggested in 1917 that her visions reflected migraine with aura; the proposal was made widely known by the neurologist Oliver Sacks, who in his book Migraine called Hildegard’s visions “indisputably migrainous,” comparing the geometric patterns in the illuminations of her Scivias to the scintillating scotoma of classic visual aura.

It is important to be precise about the status of this claim. The migraine reading of Hildegard’s visions is a retrospective interpretation, not an established fact — Hildegard left no medical diagnosis, and historians of medicine have rightly cautioned that diagnosing a twelfth-century mystic across nine hundred years is speculative and shaped by the assumptions of the diagnoser. Presented honestly as a hypothesis, however, it remains one of the most evocative episodes in the cultural history of the disease: a possible glimpse of what migraine aura looked like from the inside, recorded by someone who experienced it as the radiance of the divine rather than as a symptom.

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The 19th Century: Liveing and the Nerve-Storm

The nineteenth century was when migraine began to be studied as a problem of the nervous system in its own right, and the landmark is unambiguous. In 1873, the English physician Edward Liveing (1832–1919) published On Megrim, Sick-Headache, and Some Allied Disorders: A Contribution to the Pathology of Nerve-Storms — the first major book-length treatise devoted to migraine. Its importance is twofold: it gathered and analyzed migraine systematically, and it advanced a boldly neural theory of the disease at a time when explanations were still largely speculative.

Liveing proposed that migraine was not, at root, a disorder of the blood vessels but a disturbance of the nervous system itself — an inherited tendency for nerve force to build up and then discharge explosively in what he called a “nerve-storm.” He saw migraine as kin to other paroxysmal nervous disorders, and drew a deliberate parallel with epilepsy, arguing that both arose from sudden central-nervous-system discharges and could even alternate in the same patient. This neurogenic view influenced the founders of modern neurology — notably Sir William Gowers, who adopted a broadly neural account of headache — and, although the vascular theory would soon eclipse it for much of the next century, Liveing’s core intuition that migraine is fundamentally a brain disorder has been strikingly vindicated by modern research.

The same century also sharpened the description of the visual aura. The English physician Hubert Airy (1838–1903) published in 1870 a careful first-person account and drawings of his own expanding, shimmering “teichopsia” (fortification spectrum), often regarded as the first definitive English-language description of the migraine visual aura — a clinical complement to Liveing’s broader theory.

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The Vascular Theory: Harold Wolff’s Era

In the middle of the twentieth century, the pendulum swung firmly toward the blood vessels, and for decades the vascular theory of migraine dominated teaching and practice. Its central figure was the American neurologist Harold G. Wolff (1898–1962), working with colleagues including John R. Graham. In a famous 1938 demonstration, Graham and Wolff showed that injecting ergotamine — a blood-vessel constrictor — reduced both the pulsation of the scalp arteries and the intensity of the headache in parallel. By the early 1940s Wolff had built this into a coherent model.

The vascular theory held, in essence, that the aura was caused by an initial constriction of cerebral arteries (reducing blood flow to the brain and producing the visual symptoms), followed by a rebound dilation of arteries — especially branches of the external carotid supplying the scalp and meninges — whose throbbing distension produced the pulsating pain. It was an elegant, mechanically intuitive story, and it neatly explained why vasoconstricting drugs like ergotamine helped. For roughly half a century it was the standard explanation taught to physicians.

Yet the vascular theory was, in the end, largely superseded. Careful blood-flow studies failed to confirm that the timing and pattern of vessel changes matched the symptoms; auras were shown to track a wave moving across the cortex rather than the territory of any single artery; and the throbbing pain did not reliably correspond to arterial pulsation. One widely cited 2009 review in the journal Brain summed up the verdict in its title: the vascular theory was “a great story wrecked by the facts.” This shift — from vessels to brain — is the single most important conceptual change in the modern history of migraine, and it returned the field, in a sense, to the neural intuition of Liveing.

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The Neural Turn: Cortical Spreading Depression

The key that unlocked the neural understanding of the aura was discovered, almost by accident, in a physiology laboratory. In 1944, the Brazilian physiologist Aristides Leão (1914–1993), then a graduate student at Harvard studying experimental epilepsy in rabbits, observed something unexpected: after he stimulated the cortex, a wave of suppressed electrical activity spread slowly outward across the brain’s surface at roughly 3 to 6 millimetres per minute. He named it spreading depression; today it is known as cortical spreading depression (CSD), or “Leão’s spreading depression.”

The connection to migraine aura was made over the following decades. As early as 1941 the psychologist Karl Lashley, charting the march of his own scintillating scotoma across his visual field, had calculated that the underlying cortical event must advance at about 3 millimetres per minute — almost exactly the speed Leão later measured for spreading depression. The match between Lashley’s estimate and Leão’s observation is the foundation of the modern view that the aura is cortical spreading depression made visible: a self-propagating wave of intense neuronal firing followed by silence, sweeping across the visual cortex and producing the expanding shimmer-and-blind-spot that patients describe. CSD is now widely accepted as the physiological basis of the migraine aura, and it is firmly a phenomenon of neurons and glia, not of blood vessels.

This reframing was decisive. It explained the aura without recourse to artery spasm, it explained why the aura ignores arterial boundaries, and it re-grounded migraine in the brain. Any changes in blood flow that accompany the aura are now understood as consequences of the neural wave rather than its cause — the brain leading, the vessels following.

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The Trigeminovascular System and CGRP

If cortical spreading depression explained the aura, the throbbing pain of migraine needed its own neural account — and that came from the discovery of the trigeminovascular system. In 1979, the neurologist Michael Moskowitz and colleagues proposed that migraine pain arises from the trigeminal nerve — the great sensory nerve of the face and head — whose fibres wrap around the blood vessels of the meninges (the coverings of the brain). When these trigeminal fibres are activated, they release vasoactive neuropeptides directly onto the meningeal vessels, producing “neurogenic inflammation” — vessel dilation, plasma leakage, and the sensitization of pain receptors — that the brain then registers as a pounding headache. Crucially, in this model the vessel changes are driven by nerves; the nerve comes first.

The chemical messenger at the heart of this system turned out to be calcitonin gene-related peptide (CGRP), a 37-amino-acid neuropeptide carried by trigeminal pain fibres. In a landmark 1988 study, Peter Goadsby and Lars Edvinsson, with colleagues, showed that activating the trigeminovascular system released CGRP into the cranial circulation. They and others then demonstrated the clinching facts: CGRP levels rise in the blood draining the head during a migraine attack, and infusing CGRP into people who have migraine can trigger a migraine-like headache. Together, cortical spreading depression (for the aura) and the trigeminovascular CGRP system (for the pain) supplied a coherent, brain-based explanation of migraine that the old vascular theory never could — and, just as importantly, they pointed directly at new drug targets.

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From Ergotamine to Triptans to CGRP Blockers

The history of migraine treatment runs in three great waves, and each wave reflects the science of its era. The first was the age of the ergot alkaloids. Ergot — a fungus of rye with a long and dangerous folk history — yielded ergotamine, introduced for migraine in the early twentieth century (around 1906 onward) and refined as dihydroergotamine in the 1940s. Ergotamine constricts blood vessels (and acts on serotonin and other receptors), and it was precisely its vessel-narrowing effect that inspired Wolff’s vascular theory. It worked for many patients but was hard to dose and carried real cardiovascular risks.

The second wave was the triptans, and it represents one of the great therapeutic breakthroughs of modern neurology. Led by the pharmacologist Patrick Humphrey and his team at Glaxo, researchers set out deliberately to design a selective agonist of specific serotonin (5-HT₁) receptors that would act on cranial vessels and trigeminal nerves without ergotamine’s scattershot side effects. The result was sumatriptan, the first triptan, which was marketed in 1991 (first in the Netherlands; reaching the United States in 1993). Sumatriptan was transformative — a targeted, reliable, acute migraine drug — and it founded a whole class (sumatriptan, rizatriptan, zolmitriptan, and others) that remains a mainstay of acute treatment today.

The third and current wave targets CGRP directly, the fruit of the trigeminovascular discoveries. Two complementary drug families emerged. The anti-CGRP monoclonal antibodies — large, long-acting biologics given by injection to prevent attacks — arrived first: erenumab (Aimovig) became the first FDA-approved drug in this class on 17 May 2018, soon followed by fremanezumab, galcanezumab, and eptinezumab. Close behind came the gepants — small-molecule CGRP-receptor blockers taken as pills: ubrogepant (Ubrelvy, approved December 2019) and rimegepant (Nurtec, 2020), with atogepant following for prevention. For the first time, migraine had drugs designed from the ground up against its own biology — the practical payoff of the long shift from the vascular theory to the neural one.

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Legacy: A Brain Disorder, Reclaimed

Seen whole, the history of migraine is a story of a single intuition lost and recovered. The ancients located the problem in the head and described it with uncanny accuracy; Liveing in 1873 argued it was a disorder of the nervous system and likened it to epilepsy; the twentieth century detoured for some fifty years through the vascular theory; and the modern era — armed with cortical spreading depression, the trigeminovascular system, and CGRP — has firmly re-established migraine as a primary disorder of the brain, in which any vascular changes are downstream effects rather than the cause.

That reclassification is not merely academic. It carries real weight for the millions of people who live with migraine, because for centuries the disease was dismissed as “just a headache,” as nerves, or as something psychological. Establishing migraine as a concrete, mechanistically understood neurological disease — with identifiable molecules, measurable events, and drugs designed against them — has helped restore both scientific seriousness and personal dignity to a condition that is one of the leading causes of disability worldwide.

The arc also illustrates how medicine actually advances: not in a straight line, but by argument, reversal, and the stubborn insistence of facts over elegant stories. From Galen’s hemicrania to a once-a-month antibody against CGRP, the same disease has been watched, named, mis-explained, and finally understood — and the watching is not finished. For the practical side of living with migraine today — triggers, prevention, and treatment — see the main Migraine hub and its companion articles.

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Research Papers and References

The references below combine peer-reviewed historical and pathophysiological reviews (with DOIs or PubMed identifiers where confidently identified) with curated PubMed topic-search links into the wider literature. Ancient and historical primary sources — the Hippocratic writings, the works of Aretaeus and Galen, and Edward Liveing’s 1873 On Megrim — are named in the article as historical texts rather than as modern citations. Each link opens in a new tab.

Pearce JMS. Historical aspects of migraine. Journal of Neurology, Neurosurgery & Psychiatry. 1986;49(10):1097-1103. — doi:10.1136/jnnp.49.10.1097
Koehler PJ, Boes CJ. A history of non-drug treatment in headache, particularly migraine. Brain. 2010;133(8):2489-2500. — doi:10.1093/brain/awq170
Isler H, Koehler PJ, et al. Aretaeus on migraine and headache. Journal of the History of the Neurosciences. 2001;10(3):253-261. — PubMed PMID: 11770192
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
Goadsby PJ, Edvinsson L, Ekman R. Release of vasoactive peptides in the extracerebral circulation of humans and the cat during activation of the trigeminovascular system. Annals of Neurology. 1988;23(2):193-196. — doi:10.1002/ana.410230214
Goadsby PJ, Holland PR, Martins-Oliveira M, et al. Pathophysiology of migraine: a disorder of sensory processing. Physiological Reviews. 2017;97(2):553-622. — doi:10.1152/physrev.00034.2015
Edvinsson L, Haanes KA, Warfvinge K, Krause DN. CGRP as the target of new migraine therapies — successful translation from bench to clinic. Nature Reviews Neurology. 2018;14(6):338-350. — doi:10.1038/s41582-018-0003-1
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
Hippocratic and classical descriptions of migraine and visual aura (historical overview) — PubMed: Hippocrates, migraine and aura in history
Cortical spreading depression of Leão and the migraine aura — PubMed: Leão, cortical spreading depression and aura
Harold Wolff and the vascular theory of migraine (historical) — PubMed: Wolff and the vascular theory of migraine
The trigeminovascular system in migraine pathophysiology — PubMed: trigeminovascular system and migraine
Sumatriptan and the development of the triptans — PubMed: sumatriptan and triptan development
Erenumab and anti-CGRP monoclonal antibodies for migraine prevention — PubMed: erenumab and anti-CGRP antibodies

External Authoritative Resources

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Connections

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