Abstract
BackgroundThe 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).Methods and FindingsUsing 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°C and noxious heat (pain threshold+1°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.ConclusionsAltered 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.
Highlights
Defects in brainstem descending modulatory circuits may contribute to the onset of migraine, based on structural changes [1,2] and functional abnormalities in brainstem areas during migraine attacks [3,4,5]
Altered descending modulation has been postulated to contribute to migraine, leading to loss of inhibition or enhanced facilitation resulting in hyperexcitability of trigeminovascular neurons
nucleus cuneiformis (NCF) function could potentially serve as a diagnostic measure in migraine patients, even when not experiencing an attack
Summary
Defects in brainstem descending modulatory circuits may contribute to the onset of migraine, based on structural changes [1,2] and functional abnormalities in brainstem areas during migraine attacks [3,4,5]. Enhanced responses in nociceptive spinal and trigeminal neurons could result from these abnormalities, which could reflect either unusually low levels of descending inhibition [6] or high levels of descending facilitation [7,8]. In migraine, such hyperexcitability could lower the threshold of nociceptive neurons in response to meningeal inputs. If dysfunctional pain modulatory circuits exist in migraineurs, we hypothesized that functional changes should be evident in interictal (i.e. not experiencing an attack) migraine patients. 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)
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