Article

Interictal Dysfunction of a Brainstem Descending Modulatory Center in Migraine Patients

PAIN Group, Brain Imaging Center, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, United States of America.
PLoS ONE (Impact Factor: 3.23). 02/2008; 3(11):e3799. DOI: 10.1371/journal.pone.0003799
Source: PubMed

ABSTRACT The brainstem contains descending circuitry that can modulate nociceptive processing (neural signals associated with pain) in the dorsal horn of the spinal cord and the medullary dorsal horn. In migraineurs, abnormal brainstem function during attacks suggest that dysfunction of descending modulation may facilitate migraine attacks, either by reducing descending inhibition or increasing facilitation. To determine whether a brainstem dysfunction could play a role in facilitating migraine attacks, we measured brainstem function in migraineurs when they were not having an attack (i.e. the interictal phase).
Using fMRI (functional magnetic resonance imaging), we mapped brainstem activity to heat stimuli in 12 episodic migraine patients during the interictal phase. Separate scans were collected to measure responses to 41 degrees C and noxious heat (pain threshold+1 degrees C). Stimuli were either applied to the forehead on the affected side (as reported during an attack) or the dorsum of the hand. This was repeated in 12 age-gender-matched control subjects, and the side tested corresponded to that in the matched migraine patients. Nucleus cuneiformis (NCF), a component of brainstem pain modulatory circuits, appears to be hypofunctional in migraineurs. 3 out of the 4 thermal stimulus conditions showed significantly greater NCF activation in control subjects than the migraine patients.
Altered descending modulation has been postulated to contribute to migraine, leading to loss of inhibition or enhanced facilitation resulting in hyperexcitability of trigeminovascular neurons. NCF function could potentially serve as a diagnostic measure in migraine patients, even when not experiencing an attack. This has important implications for the evaluation of therapies for migraine.

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    • "Moreover, several independent functional imaging studies have reinforced the fact that the pathogenesis of migraine is related to the dysfunction of the brain stem. A series of positron emission tomographic (PET) studies consistently observed an increase in regional cerebral blood flow in the brain stem during migraine attacks [41,45-47], and the brain stem was also found to be activated in migraine patients with some stimulus detected by fMRI [48-50]. Dysfunction of the brain stem is involved in anti­nociception, extracerebral and intracerebral vascular control and sensory gating provides an explanation for many of the facets of migraine. "
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    • "Similar abnormal facilitatory changes were demonstrated using the same electrophysiological techniques in chronic extracranial painful disorders, such as fibromyalgia [18]. Based on neuroimaging studies, functional or structural changes that occur during migraine attacks have been documented in the brain regions responsible for central pain processing, such as the brain stem [7] [49] [71], trigeminal somatosensory pathway [17], primary somatosensory cortex [16], and posterior parietal cortex [41] [71]. It has been postulated that the repeated activation of the trigeminal pathway and consequently, the modular pain pathways in the periaqueductal gray matter, may promote structural changes in chronic pain conditions [4]. "
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    • "Therefore, CM might result from decompensation after over-activation of this region, which leads to loss of the hypertrophic response. It is suggested that the brainstem dysfunction may alter cortical and subcortical excitability, which then contributes to migraine evolution [25–28]. Another possibility is that frequent headache attacks might have a disadvantageous effect on neurons at the dorsal pons, leading to neuronal dysfunction or atrophy in patients with CM. "
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