One of the theories regarding the mechanism of migraine comes from observations made by Sir Thomas Lewis in 1926.1 He showed that there is a threefold reaction to local skin irritation: (1) local reaction at the site of the irritant, (2) local release of histamine at the site causing a wheal immediately around it and (3) a further release of free histamine into the circulating blood. It is well known that the intradermal injection of histamine in certain individuals will cause this second phenomenon of wheal formation, which is essentially a vasodilatation. It is generally believed that the phenomenon of migraine is precipitated by the release of histamine into the blood stream as the result of an allergic reaction and that the major attack of migraine develops only in those individuals whose tolerance to histamine is low and who would be hyperreactors at one phase of the syndrome to
BUTLER S, THOMAS WA. INTRAVENOUS HISTAMINE IN THE TREATMENT OF MIGRAINE: PRELIMINARY OBSERVATIONS. JAMA. 1945;128(3):173–175. doi:10.1001/jama.1945.02860200013004
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