Human Studies

Migraine without aura (MWoA) is a major neurological disorder with unsatisfactory adherence to current medications. Acupuncture has emerged as a promising method for treating MWoA. However, the brain mechanism underlying acupuncture is yet unclear. The present study aimed to examine the effects of acupuncture in regulating brain connectivity of the key regions in pain modulation. In this study, MWoA patients were recruited and randomly assigned to 4 weeks of real or sham acupuncture. Resting-state functional magnetic resonance imaging (fMRI) data were collected before and after the treatment. A modern neuroimaging literature meta-analysis of 515 fMRI studies was conducted to identify pain modulation-related key regions as regions of interest (ROIs). Seed-to-voxel resting state-functional connectivity (rsFC) method and repeated-measures two-way analysis of variance were conducted to determine the interaction effects between the two groups and time (baseline and post-treatment). The changes in rsFC were evaluated between baseline and post-treatment in real and sham acupuncture groups, respectively. Clinical data at baseline and post-treatment were also recorded in order to determine between-group differences in clinical outcomes as well as correlations between rsFC changes and clinical effects. 40 subjects were involved in the final analysis. The current study demonstrated significant improvement in real acupuncture vs sham acupuncture on headache severity (monthly migraine days), headache impact (6-item Headache Impact Test), and health-related quality of life (Migraine-Specific Quality of Life Questionnaire). Five pain modulation-related key regions, including the right amygdala (AMYG), left insula (INS), left medial orbital superior frontal gyrus (PFCventmed), left middle occipital gyrus (MOG), and right middle cingulate cortex (MCC), were selected based on the meta-analysis on brain imaging studies. This study found that 1) after acupuncture treatment, migraine patients of the real acupuncture group showed significantly enhanced connectivity in the right AMYG/MCC-left MTG and the right MCC-right superior temporal gyrus (STG) compared to that of the sham acupuncture group; 2) negative correlations were established between clinical effects and increased rsFC in the right AMYG/MCC-left MTG; 3) baseline right AMYG-left MTG rsFC predicts monthly migraine days reduction after treatment. The current results suggested that acupuncture may concurrently regulate the rsFC of two pain modulation regions in the AMYG and MCC. MTG and STG may be the key nodes linked to multisensory processing of pain modulation in migraine with acupuncture treatment. These findings highlighted the potential of acupuncture for migraine management and the mechanisms underlying the modulation effects.

The ketogenic diet (KD) is gaining attention as a preventive treatment for migraine, which is sustained by many pre-clinical and clinical data. KD is also used for weight loss, and there is a relation between migraine and weight excess, but it is speculated that KD efficacy on migraine may go beyond this effect. We conducted a retrospective observational study on 23 migraine patients who received a KD and were evaluated at the baseline and then after 3 months both from a neurological and a nutritional point of view, including body mass composition analysis. We observed a reduction in monthly headache days (12.5 ± 9.5 vs. 6.7 ± 8.6; < 0.001) and in days of acute medication intake (11.06 ± 9.37 vs. 4.93 ± 7.99; = 0.008). We also observed a reduction in patients' weight (73.8 ± 15.2 vs. 68.4 ± 14.6; < 0.001) and BMI (26.9 ± 6.2 vs. 23.7 ± 8.1; < 0.001) with a decrement of the fat mass (28.6 ± 12.5 vs. 20.6 ± 9.8; < 0.001). Patients who responded to KD and those who did not had no differences with respect to weight or fat mass loss. These data corroborate the utilization of KD as a preventive treatment for migraine and suggest that the efficacy of such an intervention is not only due to weight or fat mass loss but probably relies on other mechanisms specific to KD.

The efficacy of ubrogepant 50 mg versus 100 mg daily for migraine remained controversial. We conducted a systematic review and meta-analysis to compare the efficacy and safety of ubrogepant 50 mg versus 100 mg daily on treatment in migraine patients. We have searched PubMed, EMbase, Web of science, EBSCO, Cochrane library databases and SCOPUS through March 21, 2022 for randomized controlled trials (RCTs) assessing the effect of ubrogepant 50 mg versus 100 mg on treatment efficacy in migraine patients. This meta-analysis was performed using the random-effect model. Three RCTs were included in the meta-analysis. Overall, compared with ubrogepant 100 mg in migraine patients, ubrogepant 50 mg obtained comparable pain freedom at 2 hours (OR =0.86; 95% CI =0.64 to 1.15; P = 0.310), sustained pain freedom 2-24 hours (OR =0.76; 95% CI =0.54 to 1.07; P = 0.110), photophobia absence at 2 h (OR =0.80; 95% CI =0.63 to 1.02; P = 0.070), phonophobia absence at 2 h (OR =1.07; 95% CI =0.82 to 1.40; P = 0.620) and nausea absence at 2 h (OR =1.02; 95% CI =0.79 to 1.32; P = 0.880). In terms of safety, adverse events was found to be increased in ubrogepant 100 mg as compared to ubrogepant 50 mg (OR =0.81; 95% CI =0.67 to 0.99; P = 0.040), and there was no statistical difference of serious adverse events between two groups (OR =0.87; 95% CI =0.40 to 1.91; P = 0.720). Ubrogepant 50 mg and 100 mg may be equally effective to alleviate migraine, but ubrogepant 100 mg led to increase incidence of adverse events.