Chronic migraine is a common central nervous system disorder characterized by recurrent, pulsating headaches. However, the extent and mechanisms of hypothalamic involvement in disease progression have not been thoroughly investigated. Herein, we created a chronic migraine mouse model using repeated intraperitoneal injections of nitroglycerin. We performed transcriptomic sequencing on the hypothalamus of mice with chronic migraine and control mice under normal physiological conditions, followed by differential gene set enrichment and functional analysis of the data. Additionally, we examined the intrinsic connection between chronic migraine and sleep disorders using transcriptomic sequencing data from sleep-deprived mice available in public databases. We identified 39 differentially expressed genes (DEGs) in the hypothalamus of a mouse model of chronic migraine. Functional analysis of DEGs revealed enrichment primarily in signaling transduction, immune-inflammatory responses, and the cellular microenvironment. A comparison of the transcriptomic data of sleep-deprived mice revealed two commonly expressed DEGs. Our findings indicate that the hypothalamic DEGs are primarily enriched in the PI3K/AKT/mTOR pathway and associated with the NF-kB/NLRP3/IL-1 β pathway activation to maintain the central sensitization of the chronic migraine. Chronic migraine-induced gene expression changes in the hypothalamus may help better understand the underlying mechanisms and identify therapeutic targets.

OBJECTIVE: Chronic migraine poses a global health burden, particularly affecting young women, and has substantial societal implications. This study aimed to assess the efficacy of Greater Occipital Nerve Block (GONB) in individuals with chronic migraine, focusing on the impact of local anesthetics compared with placebo.
METHODS: A meta-analysis and systematic review were conducted following the PRISMA principles and Cochrane Collaboration methods. Eligible studies included case-control, cohort, and randomized control trials in adults with chronic migraine, adhering to the International Classification of Headache Disorders, third edition (ICHD3). Primary efficacy outcomes included headache frequency, duration, and intensity along with safety assessments.
RESULTS: Literature searches across multiple databases yielded eight studies for qualitative analysis, with five included in the final quantitative analysis. A remarkable reduction in headache intensity and frequency during the first and second months of treatment with GONB using local anesthetics compared to placebo has been reported. The incidence of adverse events did not differ significantly between the intervention and placebo groups.
CONCLUSIONS: The analysis emphasized the safety and efficacy of GONB, albeit with a cautious interpretation due to the limited number of studies and relatively small sample size. This study advocates for further research exploring various drugs, frequencies, and treatment plans to enhance the robustness and applicability of GONB for chronic migraine management.

BACKGROUND: The periaqueductal gray (PAG) is at the center of a powerful descending antinociceptive neuronal network, and is a key node in the descending pain regulatory system of pain. However, less is known about the altered perfusion of PAG in chronic migraine (CM).
OBJECTIVE: To measure the perfusion of PAG matter, an important structure in pain modulation, in CM with magnetic resonance (MR) perfusion without contrast administration.
METHODS: Three-dimensional pseudocontinuous arterial spin labeling (3D-PCASL) and brain structure imaging were performed in 13 patients with CM and 15 normal subjects. The inverse deformation field generated by brain structure image segmentation was applied to the midbrain PAG template to generate individualized PAG. Then the perfusion value of the PAG area of the midbrain was extracted based on the individual PAG mask.
RESULTS: Cerebral blood flow (CBF) value of PAG in CM patients (47.98 ± 8.38 mL/100 mg min) was significantly lower than that of the control group (59.87 ± 14.24 mL/100 mg min). Receiver operating characteristic (ROC) curve analysis showed that the area under the curve was 0.77 (95% confidence interval [CI], 0.60, 0.94), and the cutoff value for the diagnosis of CM was 54.83 mL/100 mg min with a sensitivity 84.60% and a specificity 60%.
CONCLUSIONS: Imaging evidence of the impaired pain conduction pathway in CM may be related with the decreased perfusion in the PAG, which could be considered as an imaging biomarker for the diagnosis and therapy evaluation.

BACKGROUND: Migraine is a primary headache defined as moderate-to-severe pain lasting 4 to 72 h, ranking 2nd among the disabling conditions for both genders regardless of the age and the greater occipital nerve (GON) block has been reported as an efficient treatment method for migraine. The present study aims to evaluate and compare the efficiency of the two methods of GON block, i.e., the ultrasound (US)-guided technique and the landmark-based technique.
METHODS: Having a prospective and randomized design, the study assigned the patients with chronic migraine into two groups after which a neurologist performed landmark-based GON block in the first group while an algologist performed US-guided GON block in the second group. During the 3-month follow-up period, the number of days with pain, the duration of pain, the number of analgesic drugs taken in a month, and Visual Analogue Scale (VAS) scores were compared with the values ​​before treatment and at the 1st week, 1st month, and 3rd month after treatment.
RESULTS: US-guided GON block group included 34 patients while there were 32 patients in the landmark-based GON block group. US-guided GON block group showed significantly reduced VAS scores and frequency of attacks compared to the landmark-based GON block group at Month 1 after the procedure. After a 3-month follow-up period of the two groups, the frequency of attacks, analgesic intake and the duration of attacks were lower in both groups compared to the baseline. At 3-month follow-up, the mean of VAS scores decreased from 9,47 ± 2,69 to 4,67 ± 1,9 in US-guided GON block group and from 9,46 ± 0,98 to 7 ± 2,5 in the landmark-based GON block group.
CONCLUSIONS: It was determined that both US-guided and landmark-based GON block were efficient techniques in patients with chronic migraine. US-guided GON block technique resulted in lower VAS scores, shorter durations of pain, lower frequencies of attack, and lower intake of analgesics compared to the landmark-based GON block technique.

Migraine causes debilitating headaches and significantly impacts quality of life. Effective migraine-specific treatments have been lacking until the advent of monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) receptors, which have expanded therapy options for migraine treatment. This study explores the short- and long-term efficacy and safety of erenumab in migraine treatment. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 criteria guided this systematic review. Five databases - PubMed, PubMed Central, Google Scholar, ScienceDirect, and Sage Journal - were searched for published, freely accessible, full-text articles in English from the past five years. Eligible patients included those with episodic or chronic migraines who received erenumab intervention. From an initial search yielding 680 relevant studies, 12 prospective observational cohort studies were selected after assessing the risk of bias through the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. All included studies demonstrated a significant reduction in monthly migraine days (MMDs) by the end of the treatment period, with mild adverse effects observed. No significant short-term or long-term safety concerns were identified.

BACKGROUND: Migraine is a neurological disorder characterized by complex, widespread, and sudden attacks with an unclear pathogenesis, particularly in chronic migraine (CM). Specific brain regions, including the insula, amygdala, thalamus, and cingulate, medial prefrontal, and anterior cingulate cortex, are commonly activated by pain stimuli in patients with CM and animal models. This study employs fluorescence microscopy optical sectioning tomography (fMOST) technology and AAV-PHP.eB whole-brain expression to map activation patterns of brain regions in CM mice, thus enhancing the understanding of CM pathogenesis and suggesting potential treatment targets.
METHODS: By repeatedly administering nitroglycerin (NTG) to induce migraine-like pain in mice, a chronic migraine model (CMM) was established. Olcegepant (OLC) was then used as treatment and its effects on mechanical pain hypersensitivity and brain region activation were observed. All mice underwent mechanical withdrawal threshold, light-aversive, and elevated plus maze tests. Viral injections were administered to the mice one month prior to modelling, and brain samples were collected 2 h after the final NTG/vehicle control injection for whole-brain imaging using fMOST.
RESULTS: In the NTG-induced CMM, mechanical pain threshold decreased, photophobia, and anxiety-like behavior were observed, and OLC was found to improve these manifestations. fMOST whole-brain imaging results suggest that the isocortex-cerebral cortex plate region, including somatomotor areas (MO), somatosensory areas (SS), and main olfactory bulb (MOB), appears to be the most sensitive area of activation in CM (P < 0.05). Other brain regions such as the inferior colliculus (IC) and intermediate reticular nucleus (IRN) were also exhibited significant activation (P < 0.05). The improvement in migraine-like symptoms observed with OLC treatment may be related to its effects on these brain regions, particularly SS, MO, ansiform lobule (AN), IC, spinal nucleus of the trigeminal, caudal part (Sp5c), IRN, and parvicellular reticular nucleus (PARN) (P < 0.05).
CONCLUSIONS: fMOST whole-brain imaging reveals c-Fos + cells in numerous brain regions. OLC improves migraine-like symptoms by modulating brain activity in some brain regions. This study demonstrates the activation of the specific brain areas in NTG-induced CMM and suggests some regions as a potential treatment mechanism according to OLC.

UNASSIGNED: Migraine is a debilitating neurological disorder, with a wide range of symptoms and disease burden, underscoring the heterogeneity of patients\' disease characteristics and treatment needs. To characterize the profile of migraine patients in the US who may be eligible for preventive treatment with an anti-CGRP pathway mAb and to better understand treatment patterns and real-world use of acute and preventive medications for migraine, we conducted a retrospective cohort study of adult patients.
UNASSIGNED: These patients were identified as having migraine using diagnosis codes or migraine-specific medication use (first = index) in the IQVIA PharMetrics® Plus database. Patients were required to have ≥ 12 months of continuous enrollment in medical and pharmacy benefits prior to index (baseline) and after index (follow-up). Patients were stratified into chronic migraine (CM) and non-chronic migraine (non-CM) by diagnosis codes. Based on acute migraine-specific medication dispensing data in the follow-up period, non-CM patients were divided into 3 cohorts: highest, middle, and lowest tertile of total units of dispensed acute migraine-specific medication (gepants, ditans, ergot derivatives, and triptans). Migraine medication use was captured in the baseline and follow-up periods.
UNASSIGNED: A total of 22,584 CM and 216,807 non-CM patients (72,269 patients in each tertile) were identified and included in the study. Over the follow-up, CM patients had a mean of 70 units of acute migraine-specific medications dispensed, while the highest, middle, and lowest tertile of non-CM patients had a mean of 92, 29, and 10 units, respectively. Anti-calcitonin gene-related peptide pathway mAbs were dispensed for 28.9% of CM patients, and for 6.9%, 4.1%, and 2.9% of non-CM patients in the highest, middle, and lowest tertiles, respectively.
UNASSIGNED: A lower proportion of non-CM patients had use of anti-calcitonin gene-related peptide pathway mAbs compared to CM patients, confirming the unmet need with appropriate preventive medication. There appears to be a persistent gap in management of patients without a diagnosis of CM who are dispensed high quantities of acute migraine-specific medications.

OBJECTIVE: The objective of this study was to describe and discuss patterns of migraine medication use in the entire Norwegian population.
METHODS: In this nationwide, observational study, all individuals with a migraine-related prescription between 2010 and 2020 were identified using the Norwegian Prescription Database. The outcomes of interest were the incidence and 1-year prevalence of migraine medication users, as well as individuals with triptan overuse. Patterns of medication use were statistically compared between women and men adjusted for age, year of treatment start, comorbidities and county of residence calculating adjusted odds ratios (aOR) with 95% confidence intervals (CI).
RESULTS: We identified 327,904 migraine medication users. The incidence ranged from 0.39% to 0.46%, and the 1-year prevalence increased from 1.99% to 2.99%. Preventive use increased >50% during the study period. Preventives were significantly more often prescribed to women than to men (39.72% vs. 33.75%; aOR 1.41, 95% CI 1.38 to 1.44). Triptan overuse was significantly more common among women, but women with overuse were more often using preventives, as compared to men (56.64% vs 52.69%; aOR = 1.43, 95% CI 1.37 to 1.49).
CONCLUSIONS: The prevalence of medically treated migraine is low. Overuse of triptans is frequent, especially among women. Clinicians should be encouraged to try out different triptans, recognize triptan overuse, and prescribe preventives when indicated.

OBJECTIVE: To qualitatively and quantitatively summarize the evidence for the use of onabotulinumtoxinA injections in children and adolescents with migraine.
BACKGROUND: There are limited evidence-based treatment options for youth with migraine, especially youth with chronic migraine (CM). OnabotulinumtoxinA injections are an established evidence-based treatment for adults with CM. While several studies have assessed their safety and efficacy among adolescents with CM, there are no published systematic reviews summarizing the pediatric evidence.
METHODS: We carried out a systematic review, reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis, aiming to identify studies that included five or more children and adolescents aged ≤18 years with a diagnosis of migraine, who were treated with ≥50 units (U) of onabotulinumtoxinA and had outcomes assessed ≥4 weeks after one or more injection cycle. Both observational studies and randomized controlled trials (RCTs) were eligible for inclusion. Two investigators independently carried out the first (titles and abstracts) and second (full text) screening stages, as well as data extraction and quality appraisal. The American Academy of Neurology risk of bias grading scheme was used to assess study risk of bias. Studies with adequate data were pooled using random effects meta-analyses, and Hedge\'s g standardized mean differences with 95% confidence intervals (CIs) were generated to estimate the effect sizes of the continuous outcomes included. Studies lacking data required for meta-analysis were summarized qualitatively.
RESULTS: We screened 634 studies and included 14 studies comprising 491 participants, of whom 489 had CM. Two studies were RCTs, 12 were observational uncontrolled studies, and all but one study included only youth with CM. Five Class IV observational uncontrolled studies were amenable to pooling in meta-analyses. After a mean of 2-2.6 injection cycles, headache frequency was shown to decrease significantly after treatment with onabotulinumtoxinA (Hedge\'s g = 0.97, 95% CI 0.58-1.35; p < 0.0001), as did severity (Hedge\'s g = 1.24, 95% CI 0.55-1.94; p = 0.0005), with both estimates having a large effect size magnitude. A Class I parallel-group RCT of one injection series (155 U, 74 U, or placebo), powered to detect a change in 4 headache days per month, did not find outcome differences between the active and placebo treatment arms. A Class IV crossover RCT showed superiority of active (155 U) versus placebo injections. The remaining Class IV observational studies that were excluded from the meta-analyses all showed improved outcomes with onabotulinumtoxinA injections over time. No serious adverse events related to treatment occurred.
CONCLUSIONS: OnabotulinumtoxinA injections have established safety for use in children and adolescents with CM and are likely effective in reducing headache frequency and severity over time. However, in the absence of an adequately powered parallel-group RCT assessing the efficacy of multiple injection cycles, it remains unclear if this intervention is superior to placebo.

OBJECTIVE: To confirm a previously reported association of TRPV1 rs8065080 with the risk of transformation from episodic (EM) to chronic migraine (CM) and to extend knowledge about the role of other TRPV1 single nucleotide polymorphisms (SNPs), we first investigated the impact of three TRPV1 SNPs (rs8065080, rs222747 and rs222749) on the risk of migraine chronification in a case-control study. A systematic review and meta-analysis were then conducted to summarize the accumulated findings.
METHODS: Genotyping of the selected TRPV1 SNPs was performed using TaqMan real-time PCR in 167 EM and 182 CM participants. Crude and adjusted odds ratios with associated 95% confidence intervals were calculated in the log-additive, dominant, and recessive genetic models. A comprehensive literature search was performed in PubMed, Web of Knowledge, Cochrane Library, and OpenGrey until February 2024.
RESULTS: In our case-control study, no association was found between TRPV1 SNPs and the risk of migraine chronification, both in the unadjusted logistic regression models and after adjustment for confounding clinical variables. The results of the meta-analysis with a total of 241 participants with EM and 223 with CM confirmed no association between TRPV1 SNPs and the risk of migraine chronification in any of the genetic models tested.
CONCLUSIONS: The results of the present case-control study and meta-analysis exclude a major role of TRPV1 rs8065080, rs222747, and rs222749 as risk factors for migraine chronification. However, further research is needed to investigate the gene-gene and gene-environment interactions of TRPV1 SNPs on the risk of transformation from episodic to chronic migraine.