Interictal alterations of the trigeminal somatosensory pathway and periaqueductal gray matter in migraine

Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Neuroreport (Impact Factor: 1.52). 04/2007; 18(4):301-5. DOI: 10.1097/WNR.0b013e32801776bb
Source: PubMed


Migraine has been traditionally considered a nonprogressive, paroxysmal disorder with no brain abnormalities between attacks. We used diffusion tensor imaging to examine interictal diffusion properties of the brains of migraineurs with aura, migraineurs without aura and matched healthy controls. Areas of lower fractional anisotropy were present in migraineurs along the thalamocortical tract. In addition, migraineurs with aura had lower fractional anisotropy in the ventral trigeminothalamic tract, and migraineurs without aura had lower fractional anisotropy in the ventrolateral periaqueductal grey matter. Our results indicate the presence of permanent interictal changes in migraineurs, pointing to an effect of migraine on the trigeminal somatosensory and modulatory pain systems.

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    • "Moreover, previous studies using different MRI measures, such as quantitative T1 and T2 , magnetization transfer ratio, and fractional anisotropy, have suggested microstructural alterations in the thalamus of patients with migraine with aura (MwA) (Granziera et al., 2014), without aura (MwoA) (Coppola et al., 2014), or in both subgroups (DaSilva et al., 2007). However, other structural MRI studies did not detect significant differences between patients with migraine and healthy subjects in terms of global thalamic volume or local thalamic gray matter density (Rocca et al., 2006; Kim et al., 2008; Valfrè et al., 2008; Granziera et al., 2014). "
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    ABSTRACT: The thalamus contains third-order relay neurons of the trigeminal system, and animal models as well as preliminary imaging studies in small cohorts of migraine patients have suggested a role of the thalamus in headache pathophysiology. However, larger studies using advanced imaging techniques in substantial patient populations are lacking. In the present study, we investigated changes of thalamic volume and shape in a large multicenter cohort of patients with migraine. High-resolution T1-weighted MRI data acquired at 3 tesla in 131 patients with migraine (38 with aura; 30.8 ± 9 years old; 109 women; monthly attack frequency: 3.2 ± 2.5; disease duration: 14 ± 8.4 years) and 115 matched healthy subjects (29 ± 7 years old; 81 women) from four international tertiary headache centers were analyzed. The thalamus and thalamic subnuclei, striatum, and globus pallidus were segmented using a fully automated multiatlas approach. Deformation-based shape analysis was performed to localize surface abnormalities. Differences between patients with migraine and healthy subjects were assessed using an ANCOVA model. After correction for multiple comparisons, performed using the false discovery rate approach (p < 0.05 corrected), significant volume reductions of the following thalamic nuclei were observed in migraineurs: central nuclear complex (F(1,233) = 6.79), anterior nucleus (F(1,237) = 7.38), and lateral dorsal nucleus (F(1,238) = 6.79). Moreover, reduced striatal volume (F(1,238) = 6.9) was observed in patients. This large-scale study indicates structural thalamic abnormalities in patients with migraine. The thalamic nuclei with abnormal volumes are densely connected to the limbic system. The data hence lend support to the view that higher-order integration systems are altered in migraine.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 10/2015; 35(40):13800-13806. DOI:10.1523/JNEUROSCI.2154-15.2015 · 6.34 Impact Factor
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    • "In conjunction with alterations in the ascending pathways, evidence suggests that the descending pain modulatory pathway in TMD (and other musculoskeletal/inflammatory pain conditions) is also affected (Bragdon et al., 2002; Kashima et al., 1999; King et al., 2009, Linnman et al., 2012). Interestingly, the most significant area of MD difference in TMD subjects was located in the PAG, a region shown to display anatomical changes in other chronic pain conditions (DaSilva et al., 2007; Rocca et al., 2006; Seminowicz et al., 2010). The PAG did not display grey matter volume changes, suggesting that it may undergo subtle microstructural changes such as reduced dendritic fields or dendritic spine numbers whilst preserving neural numbers. "
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    ABSTRACT: Accumulated evidence from experimental animal models suggests that neuroplastic changes at the dorsal horn are critical for the maintenance of various chronic musculoskeletal pain conditions. However, to date, no study has specifically investigated whether neuroplastic changes also occur at this level in humans. Using brain imaging techniques, we sought to determine whether anatomical changes were present in the medullary dorsal horn (spinal trigeminal nucleus caudalis) in subjects with the chronic musculoskeletal pain. In twenty-two subjects with painful temporomandibular disorders (TMDs) and forty pain-free controls voxel based morphometry of T1-weighted anatomical images and diffusion tensor images were used to assess regional grey matter volume and microstructural changes within the brainstem and, in addition, the integrity of ascending pain pathways. Voxel based morphometry revealed significant regional grey matter volume decreases in the medullary dorsal horn, in conjunction with alterations in diffusivity properties, namely an increase in mean diffusivity, in TMD subjects. Volumetric and mean diffusivity changes also occurred in TMD subjects in regions of the descending pain modulation system, including the midbrain periaqueductal grey matter and nucleus raphe magnus. Finally, tractography revealed altered diffusivity properties, namely decreased fractional anisotropy, in the root entry zone of the trigeminal nerve, the spinal trigeminal tract and the ventral trigeminothalamic tracts of TMD subjects. These data reveal that chronic musculoskeletal pain in humans is associated with discrete alterations in the anatomy of the medullary dorsal horn, as well as its afferent and efferent projections. These neural changes may be critical for the maintenance of pathological pain. Copyright © 2015. Published by Elsevier Inc.
    NeuroImage 05/2015; 117. DOI:10.1016/j.neuroimage.2015.05.014 · 6.36 Impact Factor
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    • "Another important result of our study is that a number of thalamic nuclei exhibited different microstructural properties in MWA patients compared with MWoA patients and HC (Figs. 3 and 4). Previous work from our group evidenced lower fractional anisotropy in a region possibly corresponding to the vpm thalamic nucleus of migraineurs with and without aura compared with people without migraine [DaSilva et al., 2007]. Our current multicontrast study suggests that broader structural alterations are present in the thalamus of patients with visual aura encompassing a broad number of thalamic nuclei. "
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    ABSTRACT: Background and objectives: The thalamus exerts a pivotal role in pain processing and cortical excitability control, and migraine is characterized by repeated pain attacks and abnormal cortical habituation to excitatory stimuli. This work aimed at studying the microstructure of the thalamus in migraine patients using an innovative multiparametric approach at high-field magnetic resonance imaging (MRI). Design: We examined 37 migraineurs (22 without aura, MWoA, and 15 with aura, MWA) as well as 20 healthy controls (HC) in a 3-T MRI equipped with a 32-channel coil. We acquired whole-brain T1 relaxation maps and computed magnetization transfer ratio (MTR), generalized fractional anisotropy, and T2* maps to probe microstructural and connectivity integrity and to assess iron deposition. We also correlated the obtained parametric values with the average monthly frequency of migraine attacks and disease duration. Results: T1 relaxation time was significantly shorter in the thalamus of MWA patients compared with MWoA (P < 0.001) and HC (P ≤ 0.01); in addition, MTR was higher and T2* relaxation time was shorter in MWA than in MWoA patients (P < 0.05, respectively). These data reveal broad microstructural alterations in the thalamus of MWA patients compared with MWoA and HC, suggesting increased iron deposition and myelin content/cellularity. However, MWA and MWoA patients did not show any differences in the thalamic nucleus involved in pain processing in migraine. Conclusions: There are broad microstructural alterations in the thalamus of MWA patients that may underlie abnormal cortical excitability control leading to cortical spreading depression and visual aura.
    Human Brain Mapping 04/2014; 35(4). DOI:10.1002/hbm.22266 · 5.97 Impact Factor
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