Neurogenically mediated plasma extravasation in dura mater: Effect of ergot alkaloids

A possible mechanism of action in vascular headache

Authors

  • Stephen Markowitz,

    Corresponding author
    1. Stroke Research Laboratory, Neurosurgery and Neurology Services, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA;
    Search for more papers by this author
  • Kiyoshi Saito,

    1. Stroke Research Laboratory, Neurosurgery and Neurology Services, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA;
    Search for more papers by this author
  • Michael A Moskowitz

    1. Stroke Research Laboratory, Neurosurgery and Neurology Services, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA;
    Search for more papers by this author

  • This is the prize-winning paper in the 1987 competition for the “Enrico Greppi Award”.

Stephen Markowitz;

Abstract

C-fiber-dependent neurogenic plasma extravasation developed in the dura mater but not the brain after electric stimulation of the rat trigeminal ganglion or after chemical stimulation of perivascular axons with intravenous capsaicin, a drug that depolarizes sensory nerve fibers. C-fiber-independent extravasation also developed in this tissue after intravenous injections of substance P or neurokinin A (two constituents of unmyelinated C fibers) and after serotonin, bradykinin, or allergic challenge in presensitized animals. Intravenous dihydroergotamine or ergotamine tartrate, in doses similar to those used to treat migraine and cluster headache, prevented the stimulation-induced leakage of plasma proteins within the dura mater. Not unexpectedly, the acute administration of methysergide, a drug effective in the prophylactic treatment of headache, was inactive in this acute model. Neither acute nor chronic administration of propranolol affected stimulation-induced leakage of plasma protein. These results demonstrate that neurogenic inflammation develops within the dura mater in the rat and that ergot alkaloids prevent the process by a C-fiber-dependent mechanism.

Ancillary