The most award winning
healthcare information source.
TRUSTED FOR FOUR DECADES.
Source: Ebersberger A, et al. Is there a correlation between spreading depression, neurogenic inflammation, and nociception that might cause migraine headache? Ann Neurol. 2001;49:7-13.
The pathophysiological mechanism of migraine remains a mystery. One possible clue has been the link between migraine aura and migraine headache. In the 1940s both Lashley’s now infamous self reported scintillating scotoma moving at a rate of 2-3 mm/min and Leao’s finding of spreading oligemia across the surface of a rabbit brain at the same 2-3 mm/min implicated this phenomenon of cortical spreading depression (CSD) as the crucial step in the initiation of migraine head pain. Indeed recent work by Michael Moskowitz on neurogenic inflammation suggests the importance of CSD in migraine pain. According to the Moskowitz model,CSD could induce the depolarization and antidromic activation of trigeminal afferents surrounding meningeal blood vessels inducing cerebrovascular pain and swelling. However, the link between the CSD and this neurovascular inflammatory event has never been proven. The current study by Ebersberger and associates is an attempt to accurately discern the relationship between CSD and neurogenic inflammation.
Twenty-one rats were studied. Intracortical, epidural, and brainstem trigeminal caudal nucleus (TCN) recordings were made. There was no significant increased activity in TCN during single or multiple induced CSDs. Furthermore, there was no increased sensitivity of TCN neurons when tested to heat, von Frey threshold, and spontaneous activity before or after CSDs.
Neurogenic inflammation (NI) was quantified by a measurement of NI mediators such as CGRP and prostaglandin E2 (PGE2) in plasma dural extravasation. Neither CGRP or PGE2 were increased following individual or serial CSDs.
Ebersberger et al conclude that CSD in the cortex in not sufficient to activate the release of neuroinflammatory peptides, nor is it sufficient to activate second order neurons in TCN. The results do not support the hypothesis that CSD could activate the trigeminalvascular system leading to the neurogenic inflammation that ultimately causes migraine headache.
This elegant study on rat brains brings up several important points on migraine in humans. Indeed a thoughtful editorial in the same publication by Goadsby preceding the article summarizes the critical issues (Ann Neurol 2001;49:4-6). As Goadsby notes, the clinical observation of CSD as a transient reversible neurologic phenomenon mainly experienced as visual obscurations has appeared to be a process not in series with migraine headache but rather one that is in parallel. For example, migraine aura only accompanies migraine headache in 15-20% of cases. Only 25% of the time does the aura actually precede the headache. Rather most of the time it is concurrent or follows the onset of the headache. And finally, 10% of migraineurs report migraine aura alone without headache. The Ebersberger et al study is important in proving the negative association experimentally between CSD and the other events more closely linked to migraine pain. So as future work will likely reveal, we are going to confirm what clinicians have known implicitly for a long time; the seminal events of migraine—the aura and pain—are a separate but equal phenomenon occurring not in series but in parallel. How they are linked remains to be determined. —Jeffrey B. Reich