Ask almost anyone _ sufferer or neurologist _ what causes migraineheadaches, and the answer is likely to be: Dilation of the bloodvessels in the brain.
Not so, said neurophysiologist Andrew Strassman, of HarvardMedical School and Boston's Beth Israel-Deaconness teachinghospital.
"For many years," Strassman told BioWorld Today, "it was thought_ in fact it was considered as proven, and so written in textbooks _that migraines resulted from dilation of blood vessels in the head. Butas evidence accumulated," he added, "even in the last few years, it'sseen as less and less likely, because it doesn't look as if there is anysuch dilation during a migraine attack."
Ten percent of the U.S. population knows well what those attacks canbe like: Often, they start with dizziness, nausea, aversion to light.Then comes the throbbing migraine headache proper, with a curiousduality: It often affects only one side of the head.
Female victims outnumber males by three to one, Strassman pointedout. Whether there is a hereditary, genetic component to migraine, heobserved, "is an active area of study, not resolved."
He observed that statistics of incidence and prevalence are ballparkonly, because, "Many people with migraine headache do not seekmedical treatment. Or if they did at one time, they gave it up."
With the blood vessel dilation theory now debatable, his alternativehypothesis for migraine is the increased sensitization to mechanicalstimulation of sensory nerve endings in the brain. As proposed invarious theories," he suggested, "the sensory nerve endings becomeabnormally sensitive, so that normally innocuous pulsations of bloodvessels in the brain become painful." Hence, the typical throbbingmigrainous agony.
By sensitization, Strassman means "that neurons now respond to astimulus that initially produced no activation."
Where there is a measure of agreement in the debate is that the venueof migraine is at the brain's outer protective membranous sheath, thedura mater (Latin for "tough mother,") and the meninges. "Themeninges," Strassman explained, "carry the arterial blood supply tothe brain, and pass the venous blood back to the heart by way ofspaces _ or sinuses _ between the dura's two layers."
He observed: "That sensory innervation of the meninges is probablyan important clue to the mechanism of migraine. One of the mostimportant lines of evidence on this whole issue of headachemechanism," he continued, "comes from awake patients undergoingneurosurgery under local anesthetic. They report that stimulation ofthe meninges is painful, particularly around the blood vessels.Paradoxically," he added, "the brain itself doesn't give rise to anysensation, when stimulated in an awake patient."
Strassman is first author of an article in today's Nature, titled:"Sensitization of meningeal sensory neurons and the origin ofheadaches."
In anesthetized rats, he performed "minimal surgery, namely, removalof a small area of bone from the skull, about four millimeters indiameter. This simply gave access," he explained, "to a spot on themeninges that I can stimulate."
He then looked in the trigeminal ganglion _ a key neuronal junctionbox under the brain _ for one of the very few neurons that innervate,or send out their nerve endings, to a spot on the meninges around theblood vessels. "The vast majority of trigeminal ganglion cells andnerve fibers," Strassman pointed out, "innervate the face, not theintracranial meninges."
Having located one such neuron, he proceeded to stimulate it bytickling the meningeal membrane with a von Frey monofilament. Thisis the same device that neurologists use in their offices to stroke thepalm, sole or other skin surfaces of a patient for sensory responses.
"On a human," Strassman observed, "one can determine where theirsensory threshold is, or whether there's a region of their body that hasa sensory loss. In my experiment," he continued, "I applied amechanical stimulus, simply indenting the surface of the dura with acontrolled, quantifiable force, to determine a mechanical threshold."
The bull's eye of his monofilament lies just above the sinuses in thedura, that is, the space between its upper and lower layers that acts asa unique blood vessel without walls, to carry off the venous blood.
The key finding of this work, Strassman said, "is, first, that I found aphenomenon or property of these nerve endings, which in fact hasbeen hypothesized for many years, based on symptoms of headache,namely, increased sensitivity to mechanical stimulation."
In real life, it models such stimulation as shaking, coughing or asudden head movement, which may worsen a migraine attack.Strassman emphasizes that his animal experiments "don't have adirect connection to migraine; any such relationship is indirect andspeculative."
But he added: "This work helps to focus attention on the nerveendings, and it also opens up a line of attack on the question ofheadache mechanism, asking more directly: What stimuli can actuallyactivate the nerve endings, and what kinds of anti-migraine drugs _in use or in development _ can modify or block that activation?"
The newest anti-migraine agent, Strassman went on, "is sumatriptan,an agonist to the neurotransmitter, serotonin. In fact, one of the bigsubfields in headache research," he observed, "is to characterize therole of serotonin receptors, and figure out one that might be evenmore effective in blocking migraine."
Sumatriptan, he observed, "is given abortively, that is, to abort ratherthan forestall a migraine attack. It's fairly effective in about 70percent of people who take it during the headache."
He concluded: "One of the next experiments I'll do is to put somesumatriptan onto the nerve endings, and see what it does to them. Inwhat way it blocks their activation and sensitization. If it does, thatwould be very interesting." n
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.