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. 2014 Oct;34(12):947-58.
doi: 10.1177/0333102414526069. Epub 2014 Mar 13.

Enhanced pain-induced activity of pain-processing regions in a case-control study of episodic migraine

Affiliations

Enhanced pain-induced activity of pain-processing regions in a case-control study of episodic migraine

Todd J Schwedt et al. Cephalalgia. 2014 Oct.

Abstract

Objective: The objective of this study was to identify brain regions having aberrant pain-induced activation in migraineurs, thereby gaining insight into particular aspects of pain processing that are atypical in migraineurs.

Methods: Functional magnetic resonance imaging assessed whole brain responses to painful heat in 24 adult episodic migraineurs who were at least 48 hours pain free and 27 healthy controls. Regions differentially activated in migraineurs compared to controls were identified. Activation intensities in these regions were correlated with headache frequency, number of migraine years, and time to next migraine attack.

Results: Migraineurs had greater pain-induced activation of lentiform nucleus, fusiform gyrus, subthalamic nucleus, hippocampus, middle cingulate cortex, premotor cortex, somatosensory cortex, and dorsolateral prefrontal cortex, and less activation in precentral gyrus and superior temporal gyrus. There were significant correlations between activation strength and headache frequency for middle cingulate (r = 0.627, p = 0.001), right dorsolateral prefrontal cortex (r = 0.568, p = 0.004), left fusiform gyrus (r = 0.487, p = 0.016), left precentral gyrus (r = 0.415, p = 0.044), and left hippocampus (r = 0.404, p = 0.050) and with number of migraine years for left fusiform gyrus (r = 0.425, p = 0.038). There were no significant correlations between activation strength and time to next migraine attack.

Conclusions: The majority of regions with enhanced pain-induced activation in headache-free migraineurs participate in cognitive aspects of pain perception such as attending to pain and pain memory. Enhanced cognitive pain processing by migraineurs might reflect cerebral hypersensitivity related to high expectations and hypervigilance for pain.

Keywords: Migraine; cognitive pain processing; functional magnetic resonance imaging; headache; pain.

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Figures

Figure 1
Figure 1. MRI Paradigm
During each of 3 fMRI runs, subjects were exposed to auditory cues followed either by no stimulation (3 times) or moderately painful heat stimulation (3 times) applied to the skin of the left forearm. The order of stimuli was randomized. Thus, data from each subject were derived from a total of 9 auditory cues followed by painful stimuli and 9 auditory cues followed by no stimuli.
Figure 2
Figure 2. Noxious Heat Induced Shared Activations
As anticipated, numerous regions of the “pain matrix” were commonly activated in response to moderate pain in migraine and control subjects, including anterior insula, middle insula, posterior insula, thalamus, anterior cingulate cortex, middle cingulate cortex, posterior cingulate cortex, midbrain, dorsal pons, medulla, cerebellum, somatosensory cortex, precentral gyrus, supplementary motor area, lentiform nucleus, temporal pole, prefrontal cortex, basal ganglia, hippocampus, and parahippocampal gyrus (p<.05, family-wise error corrected, cluster threshold corrected >10 voxels). Numbers next to each axial slice represent the Z-coordinate. Slices are shown with the right side of the brain on the right.
Figure 3
Figure 3. Noxious Heat Induced Activations Differing Between Migraine and Control Subjects
Several regions differentially activated in migraine subjects compared to control subjects (p<.005, cluster corrected). Voxels colored red were more strongly activated in migraine subjects compared to control subjects. Voxels colored blue were more strongly activated in control subjects compared to migraine subjects. Coordinates, max z-stats, and number of voxels for each voxel cluster are reported in Table 2. Numbers next to each axial slice represent the Z-coordinate. Slices are shown with the right side of the brain on the right. DLPFC = dorsolateral prefrontal cortex.
Figure 4
Figure 4. Correlations between Pain-Induced Activation and Headache Frequency
Pain induced activation of the middle cingulate, right dorsolateral prefrontal cortex, left fusiform gyrus, and left hippocampus significantly correlated (p<.05, uncorrected) with headache frequency (days per month with headache). Following Benjamini-Hochberg correction for multiple comparisons allowing for a false-discovery rate of 5%, correlations with the middle cingulate and right dorsolateral prefrontal cortex were still significant. DLPFC = dorsolateral prefrontal cortex.

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