By Kathryn Senior
New insights into how migraine begins are revealed this week by US researchers, who have shown that cortical spreading depression (CSD), a wave of depolarisation that spreads across the cerebral cortex, activates afferent fibres with the trigeminal nerve. The CSD has long been associated with the visual disturbance–the aura–that many people with migraine report 20-30 min before a headache starts.
Hayrunnisa Bolay (Massachusetts General Hospital, Boston, MA, USA) and colleagues investigated the effects of an experimentally induced CSD in rats using laser speckle-contrast imaging. This technique generates two-dimensional maps of blood flow within the cerebral cortex, pial vessels, and middle meningeal artery. CSD was initiated using a pin-prick to the cortical surface and relative blood flow maps were generated at various time points. Blood flow in the middle meningeal artery was selectively increased, with a peak reached after 15 min. Further studies in rats with unilateral transection of the trigeminal branch that innervates the meninges revealed that this increased blood flow was dependent on trigeminal nerve stimulation. This stimulation leads also to plasma protein leakage within the dura mater via a neurokinin-1-receptor mediated mechanism (Nat Med 2002; 8: 136-42).
“This study provides the first experimental evidence that intense brain activity promotes reflex dilation of large extracerebral arteries”, comments senior researcher Michael Moskowitz. “In this model, dilated blood vessels did not cause the headache pain but rather it developed in response to trigeminal brain stem reflexes stimulated by triggering events within brain.”
The specific hypotheses proposed in the study are testable in people who have migraines, and Moskowitz predicts that further studies in humans may uncover novel mechanisms by which comorbidity events and “triggers” (eg, stress, depression, lack of sleep, and some drugs) influence susceptibility to migraine attacks.
Constantino Iadecola (Weill Medical Center of Cornell University, New York, NY, USA), author of an accompanying commentary (Nat Med 2002; 8: 110-11), says that this work also opens the way for new therapeutic approaches for migraine with aura. Moskowitz agrees but warns that “CSD probably comes and goes too quickly for drug treatments to be effective acutely”. Nevertheless, this mechanism could provide an interesting therapeutic target for migraine prophylaxis, “especially if we understood how or why it begins, or how CSD activates the trigeminal nerve”, says Moskowitz.
Iadecola points out that any CSD interventions may not help all migraine sufferers since most do not experience an aura. “The mechanisms of the headache might be different in cases with and without aura, a possibility hinted at by genetic studies”, says Iadecola. “It may also be that the aura is not clinically evident because it involves ‘silent’ brain areas. Functional imaging studies might provide important clues on this complex problem.”
Source: The Lancet