Psychosomatic Medicine 19:199-208 (1957)
© 1957 American Psychosomatic Society

Studies in Headache

Summary of Evidence Concerning a Noxious Agent Active Locally During Migraine Headache

¹ Study Program in Human Health and the Ecology of Man and the Departments of Medicine (Neurology) and Psychiatry, the New York Hospital-Cornell Medical Center, New York, N. Y.

The thesis that during vascular headache of the migraine type there is elaborated locally in extracranial tissues through neurone activity a tissue-damaging and a pain-threshold-lowering agent is supported by the following data:

During a migraine headache attack there predictably occurred lowered deep pain thresholds and edema in those scalp areas in which headache was being experienced. Less commonly, hematomata and painful nodular accumulations of fluid occurred. The lowered deep pain thresholds and edema predictably terminated together, but often outlasted the headache itself.

The bulbar conjunctiva and its vessels on the side of the hemicrania during headache exhibited vasodilatation, edema, burning pain, reduced sensitivity to levarterenol, and increased responsiveness to acetylcholine. The occurrence and duration of vasodilatation, edema, and burning pain were not modified by either topical or parenteral administration of antihistaminic, or anticholinergic agents and were terminated at the same rate after the administration of the vasoconstrictor agents levarterenol and ergotamine tartrate.

Biopsy studies of temporal arteries removed under general anesthesia at a time when these vessels were involved in migraine headaches showed, as compared with temporal arteries removed from nonheadache subjects, perivascular and areolar edema fluid.

The injection of a spreading factor (hyaluronidase) into a tender area of the head during a migraine headache attack increased the area of tenderness fourfold.

Extracranial tissue fluid removed from sites of headache contained increased amounts of one or more amino acids, a finding compatible with the thesis that, locally, protein breakdown is augmented during headache attacks.

This fluid on intracutaneous injection induced erythema and slight lowering of skin pain thresholds. Similar pain-threshold-lowering effects were observed following injection of tissue fluid removed from induced "cold allergy" edema.

Extracranial tissue fluid removed from sites of headache exhibited the capacity to contract the rat uterus.

The combination of temporal artery dilatation (induced by immersion of subjects in warm water) and the pain-threshold-lowering effects of blister fluid injected periarterially resulted in hemicrania on the side of its injection. Serotonin injected periarterially had a similar effect. Such headache was not induced (1) by immersion alone (which induced vasodilatation); (2) by immersion with vasodilatation and the injection of saline; (3) by the injection of blister fluid or saline in the absence of induced vasodilatation. Therefore, cranial artery vasodilatation and the presence locally of a pain-threshold-lowering agent were necessary concomitants to induce headache which had many of the features of migraine headache. The presence of one or more polypeptides, the products of proteolitic activity in tissue fluids, would produce effects compatible with the recorded observations.

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