Ergot alkaloids block neurogenic extravasation in dura mater: proposed action in vascular headaches

Although the ergot alkaloids (ergots) are useful drugs for the acute treatment of migraine headaches, their mechanism of action remains obscure. When administered to rats in clinically relevant doses, ergots blocked the development of neurogenic plasma extravasation in dura mater. Plasma extravasation was induced by depolarization of perivascular axons following capsaicin injection or unilateral electrical stimulation of the trigeminal nerve. The ergot action could not be accounted for by vasoconstriction alone because neurogenic plasma leakage was not blocked by angiotensin or phenylephrine. Furthermore, ergots did not block plasma extravasation induced by administering sensory neuropeptides that mediate enhanced permeability. We propose that the therapeutic effects of ergots in vascular headaches may result from peripheral blockade of small fiber (C or A-delta)-dependent neurogenic inflammation within the dura mater.