ObjectivesTo summarize and meta-analyze studies on changes in grey matter (GM) in patients with migraine. We aimed to determine whether there are concordant structural changes in the foci, whether structural changes are concordant with functional changes, and provide further understanding of the anatomy and biology of migraine.MethodsWe searched PubMed and Embase for relevant articles published between January 1985 and November 2015, and examined the references within relevant primary articles. Following exclusion of unsuitable studies, meta-analysis were performed using activation likelihood estimation (ALE).ResultsEight clinical studies were analyzed for structural changes, containing a total of 390 subjects (191 patients and 199 controls). Five functional studies were enrolled, containing 93 patients and 96 controls. ALE showed that the migraineurs had concordant decreases in the GM volume (GMV) in the bilateral inferior frontal gyri, the right precentral gyrus, the left middle frontal gyrus and the left cingulate gyrus. GMV decreases in right claustrum, left cingulated gyrus, right anterior cingulate, amygdala and left parahippocampal gyrus are related to estimated frequency of headache attack. Activation was found in the somatosensory, cingulate, limbic lobe, basal ganglia and midbrain in migraine patients.ConclusionGM changes in migraineurs may indicate the mechanism of pain processing and associated symptoms. Changes in the frontal gyrus may predispose a person to pain conditions. The limbic regions may be accumulated damage due to the repetitive occurrence of pain-related processes. Increased activation in precentral gyrus and cingulate opposed to GMV decrease might suggest increased effort duo to disorganization of these areas and/or the use of compensatory strategies involving pain processing in migraine. Knowledge of these structural and functional changes may be useful for monitoring disease progression as well as for therapeutic interventions.

Functional connectivity (FC) has been used to investigate the pathophysiology of migraine. We aimed to identify atypical FC between the periaqueductal gray (PAG) and other brain areas in rats induced by repeated meningeal nociception. The rat model was established by infusing an inflammatory soup (IS) through supradural catheters in conscious rats. Quiescent and face-grooming behaviors were observed to assess nociceptive behavior. FC analysis seeded on the PAG was performed on rats 21 days after IS infusion. The rats exhibited nociceptive behavior correlates of human behaviors associated with migraine after IS infusion. The PAG showed increased FC with the prefrontal cortex, cingulate gyrus, and motor cortex but decreased FC with the basal ganglia, dorsal lateral thalamus, internal capsule and prelimbic cortex in the rat model. The atypical FC of the PAG with brain regions in the rat model that are involved in nociception, somatosensory processing, emotional processing, and pain modulation are consistent with the clinical data from migraineurs, indicate that resting-state FC changes in migraine patients may be a consequence of headache attacks, and further validate this rat model of chronic migraine.

We explored the atypical functional connectivity between the anterior cingulate cortex and other brain areas in rats subjected to repeated meningeal nociception. The rat model was established by infusing an inflammatory soup through supradural catheters in conscious rats. Rats were subdivided according to the frequency of the inflammatory soup infusions. Functional connectivity analysis seeded on the anterior cingulate cortex was performed on rats 21 days after inflammatory soup infusion. Glyceryl trinitrate was injected following baseline scanning in the low-frequency inflammatory soup group and magnetic resonance imaging data were acquired 1 h after the injection. The rats exhibited nociceptive behavior after high-frequency inflammatory soup infusion. The anterior cingulate cortex showed increased functional connectivity with the cerebellum in the inflammatory soup groups. The medulla showed increased functional connectivity with the anterior cingulate cortex in the ictal period in the low-frequency inflammatory soup rats. Several areas showed increased functional connectivity with the anterior cingulate cortex in the high-frequency inflammatory soup group, including the pontine tegmentum, midbrain, thalamus, corpus callosum, hippocampus, and retrosplenial, visual, sensory, and motor cortices. This study indicated that the medulla participates in the early stage of a migraine attack and may be associated with the initiation of migraine. Sensitization of the trigeminal nociceptive pathway might contribute to the cutaneous allodynia seen in chronic migraine. Brain areas important for memory function may be related to the chronification of migraine. Electrophysiological studies should examine those migraine-related areas and provide new targets for migraine treatment and prevention.

Background Galcanezumab, a humanized monoclonal antibody that binds calcitonin gene-related peptide, has demonstrated efficacy and good tolerability in patients with episodic migraine in previous phase 3 trials. We report results from the PERSIST study, which was designed to assess the efficacy and safety of galcanezumab in patients with episodic migraine from China, India, and Russia. Methods This phase 3 study was conducted at 40 centers in China (n = 26), India (n = 10), and Russia (n = 4). Eligible adult patients with episodic migraine were randomized in a 1:1 ratio to receive monthly galcanezumab 120 mg (with 240 mg loading dose) or placebo during a double-blind, 3-month treatment period. The primary endpoint was the overall mean change from baseline in monthly migraine headache days (MHDs). Key secondary endpoints were the mean proportion of patients with ≥ 50%, ≥ 75%, and 100% reductions from baseline in MHDs and mean change in the Migraine-Specific Quality of Life Questionnaire (MSQ) Role Function-Restrictive domain score. Results In total, 520 patients were randomized and received at least one dose of galcanezumab (N = 261) or placebo (N = 259). The least squares (LS) mean reduction from baseline in monthly MHDs over 3 months was significantly greater with galcanezumab compared with placebo (-3.81 days vs. -1.99 days; p < 0.0001). Significantly greater mean proportions of patients with galcanezumab versus placebo had ≥ 50%, ≥ 75%, and 100% reductions from baseline in MHDs (all p < 0.0001). The overall mean improvement from baseline in MSQ Role Function-Restrictive score over 3 months was significantly greater with galcanezumab versus placebo (p < 0.0001). There were no clinically meaningful differences between the galcanezumab and placebo group on any safety parameters except for a higher incidence of injection site pruritus (5.0% vs. 0.0%), injection site reaction (3.8% vs. 0.4%), and injection site discomfort (2.3% vs. 0.0%). TEAEs related to injection sites were mild in severity, except in 1 patient who had a moderate injection site reaction. Six serious adverse events were reported by 6 patients (2 galcanezumab, 4 placebo). Conclusions Galcanezumab 120 mg once monthly was effective and well tolerated in patients with episodic migraine from China, India, and Russia. Trial registration ClinicalTrials.gov Identifier NCT03963232 (PERSIST), registered May 24, 2019.

BackgroundThe thalamus exerts a pivotal role in pain processing and cortical excitability control and a previous voxel-based morphometry study confirmed increased volume in bilateral thalamus in medication-overuse headache (MOH). The aim of this study is to investigate altered thalamic subnuclei volume in MOH compared with normal controls, and to evaluate the relationship of each thalamic subnuclei volume with the clinical variables.MethodsHigh resolution three-dimensional T1-weighted fast spoiled gradient recalled echo MR images were obtained from 27 patients with MOH and 27 normal controls (NC). Thalamic subnuclei templates were created based on Talairach template with MNI space transformation, and the individual thalamic subnuclei templates were generated by applying the deformation field from structural image segment to the thalamic subnuclei templates, and then individual thalamci subnuclei volume were calculated.ResultsThe whole thalamus and each thalamic subnuclei presented increased volume compared with NC (P < 0.05). The correlation analysis demonstrated that the whole thalamus volume and each thalamic subnuclei volume showed a negative relationship with HAMD scores(P < 0.05), and no any correlation with HAMA, VAS score and disease duration (P > 0.05).ConclusionIncreased gray matter volume in the whole thalamus and all the thalamus subnuclei may reflect central sensitization and higher-order of pain alteration in MOH. These structural changes in the thalamus may also be influenced by mood disturbances related to the MOH.