Migraine Research Articles

Unravelling the role of beta-CGRP in inflammatory bowel disease and its potential role in gastrointestinal homeostasis

BackgroundThe role of beta calcitonin gene-related peptide (beta-CGRP) in gastrointestinal tract is obscure, but experimental models suggest an effect on the homeostasis of the intestinal mucosa. We measured beta-CGRP circulating levels in a large series of subjects with a recent diagnosis of inflammatory bowel disease (IBD), in order to assess the potential role of this neuropeptide in IBD pathogenesis.MethodsMorning serum beta-CGRP levels were measured by ELISA (CUSABIO, China) in 96 patients recently diagnosed of IBD and compared with those belonging from 50 matched healthy controls (HC) and 50 chronic migraine (CM) patients.ResultsBeta-CGRP levels were lower in patients with IBD (3.1 ± 1.9 pg/mL; 2.9 [2.4-3.4] pg/mL) as compared to HC (4.7 ± 2.6; 4.9 [4.0-5.8] pg/mL; p < 0.001) and to CM patients (4.6 ± 2.6; 4.7 [3.3-6.2] pg/mL; p < 0.001). Beta-CGRP levels in CM were not significantly different to those of HC (p = 0.92). Regarding IBD diagnostic subtypes, beta-CGRP levels for ulcerative colitis (3.0 ± 1.9pg/mL; 2.5 [2.1-3.4] pg/mL) and Crohn’s disease (3.3 ± 2.0 pg/mL; 3.2 [2.4-3.9] pg/mL) were significantly lower to those of HC (p < 0.01 and p < 0.05, respectively) and CM (p < 0.01 and p < 0.05, respectively).ConclusionsWe have found a significant reduction in serum beta-CGRP levels in patients with a recent diagnosis of all kinds of IBD as compared to two control groups without active intestinal disease, HC and CM, which may suggest a role for this neuropeptide in the pathophysiology of IBD. Our data indicate a protective role of beta-CGRP in the homeostasis of the alimentary tract.Graphical

Biomarkers and Endophenotypes of Post-traumatic Headaches.

To review existing literature on biomarkers for post-traumatic headache (PTH). Preclinical models and clinical findings have started to elucidate the biology that underlies PTH. Traumatic brain injury results in ionic flux, glutamatergic surge, and activation of the trigeminal cervical complex resulting in the release of pain neuropeptides. These neuropeptides, including calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP), play a key role in the pathophysiology of migraine and other primary headache disorders. Only two studies were identified that evaluated CGRP levels in PTH. Neither study found a consistent relationship between CGRP levels and PTH. One study did discover that nerve growth factor (NGF) was elevated in subjects with PTH. There is no conclusive evidence for reliable blood-based biomarkers for PTH. Limitations in assays, collection technique, and time since injury must be taken into account. There are multiple ideal candidates that have yet to be explored.

Causality between migraine and cardiovascular disease: a bidirectional Mendelian randomization study

BackgroundWhile growing evidence suggests a relationship between migraine and cardiovascular disease, the genetic evidence for a causal relationship between migraine and cardiovascular disease is still scarce. Investigating the causal association between migraine and cardiovascular disease is vital.MethodsWe carried out a bidirectional Mendelian randomization (MR) study including discovery samples and replication samples using publicly available genome-wide association study (GWAS) summary datasets and stringent screening instrumental variables. Four different MR techniques—Inverse variance weighted (IVW), MR ‒Egger, weighted median, and weighted mode—as well as various sensitivity analyses—Cochran’s Q, IVW radial, leave-one-out (LOO), and MR-PRESSO—were utilized to investigate the causal relationship between cardiovascular disease and migraine.ResultsThe protective causal effects of genetically predicted migraine on coronary artery disease (OR, 0.881; 95% CI 0.790–0.982; p = 0.023) and ischemic stroke (OR, 0.912; 95% CI 0.854–0.974; p = 0.006) were detected in forward MR analysis but not in any other cardiovascular disease. Consistently, we also discovered protective causal effects of coronary atherosclerosis (OR, 0.865; 95% CI 0.797–0.940; p = 0.001) and myocardial infarction (OR, 0.798; 95% CI 0.668–0.952; p = 0.012) on migraine in reverse MR analysis.ConclusionWe found a potential protective effect of migraine on coronary artery disease and ischemic stroke and a potential protective effect of coronary atherosclerosis and myocardial infarction on migraine. We emphasised epidemiological and genetic differences and the need for long-term safety monitoring of migraine medications and future research to improve cardiovascular outcomes in migraine patients.

The impact of electrotherapy on the quality of life of patients suffering from chronic migraine and cervicalgia

Objective. To evaluate the effect of electrotherapy on quality of life in patients with chronic migraine and neck pain. Material and methods. The study included 45 patients with chronic migraine and neck pain, divided into two groups: the first group (n=25) received treatment with transcutaneous electrical nerve stimulation (TENS), the second group (n=20) received botulinum toxin type A injections PREEMPT scheme. The results were assessed using the MIDAS, HIT-6 and NDI questionnaires before the start of treatment and one month after it began. Results. The use of electrotherapy caused a greater reduction in disability and improved quality of life compared to botulinum toxin. The data obtained indicate the high effectiveness of electrotherapy and the need for its further use in clinical practice to improve the condition of patients with chronic migraine and neck pain.

Pain from Internal Organs and Headache: The Challenge of Comorbidity.

Headache and visceral pain are common clinical painful conditions, which often co-exist in the same patients. Numbers relative to their co-occurrence suggest possible common pathophysiological mechanisms. The aim of the present narrative review is to describe the most frequent headache and visceral pain associations and to discuss the possible underlying mechanisms of the associations and their diagnostic and therapeutic implications based on the most recent evidence from the international literature. The conditions addressed are as follows: visceral pain from the cardiovascular, gastrointestinal, and urogenital areas and primary headache conditions such as migraine and tension-type headache. The most frequent comorbidities involve the following: cardiac ischemic pain and migraine (possible shared mechanism of endothelial dysfunction, oxidative stress, and genetic and hormonal factors), functional gastrointestinal disorders, particularly IBS and both migraine and tension-type headache, primary or secondary dysmenorrhea and migraine, and painful bladder syndrome and headache (possible shared mechanisms of peripheral and central sensitization processes). The data also show that the various visceral pain-headache associations are characterized by more than a simple sum of symptoms from each condition but often involve complex interactions with the frequent enhancement of symptoms from both, which is crucial for diagnostic and treatment purposes.

Erenumab versus topiramate: migraine-related disability, impact and health-related quality of life.

HER-MES was the first head-to-head study of erenumab against topiramate (standard of care). This post hoc analysis of the HER-MES study evaluated the effect of erenumab versus topiramate on patient-reported outcomes at week 24. Adult patients with episodic or chronic migraine (n = 777) were randomized (1:1) to monthly subcutaneous erenumab (n = 389) or daily oral topiramate (n = 388). Migraine-related disability, as measured by the Headache Impact Test 6 (HIT-6) and Short Form 36 Health Survey version 2 (SF-36v2), was analysed in the entire study cohort and true completers. In the erenumab group (vs. topiramate), significant improvements were reported in Headache Impact Test 6 total scores (composite populations, -10.88 vs. -7.72; true completers, -11.92 vs. -10.61) and a higher proportion of patients achieved a ≥5-point reduction from baseline with erenumab (composite populations, 72.2% vs. 53.9%; true completers, 79.64% vs. 71.43%). The adjusted mean change from baseline in the SF-36v2 score was greater with erenumab for both physical component summary (composite population, 5.48 vs. 3.63; true completers, 5.95 vs. 5.23) and mental component summary (composite populations, 1.00 vs. -1.18; true completers, 1.74 vs. -0.33). A higher proportion of patients on erenumab versus topiramate had a ≥5-point improvement in SF-36v2 for the physical component summary (composite populations, 47.7% vs. 37.4%; true completers, 52.1% vs. 48.9%) and mental component summary (composite populations, 25.3% vs. 16.8%; true completers, 27.3% vs. 17.7%). This post hoc analysis demonstrated that patients treated with erenumab had significant improvements in headache impact and quality of life as measured by patient-reported outcomes versus patients treated with topiramate.

Evidence-based review and frontiers of migraine therapy.

Cyclic vomiting syndrome (CVS) is identified as one of the "episodic syndromes that may be associated with migraine," along with benign paroxysmal torticollis, benign paroxysmal vertigo, and abdominal migraine. It has been proposed that CVS and migraine may share pathophysiologic mechanisms of hypothalamic activation and altered dopaminergic signaling, and impaired sensorimotor intrinsic connectivity. The past decade has brought groundbreaking advances in the treatment of migraine and other headache disorders. While many of these therapies have yet to be studied in episodic syndromes associated with migraine including CVS and abdominal migraine, the potential shared pathophysiology among these conditions suggests that use of migraine-specific treatments may have a beneficial role even in those for whom headache is not the primary symptom. This manuscript highlights newer therapies in migraine. Calcitonin gene-related peptide (CGRP) and its relation to migraine pathophysiology and the therapies that target the CGRP pathway, as well as a 5HT1F receptor agonist and neuromodulation devices used to treat migraine are briefly discussed as they may potentially prove to be useful in the future treatment of CVS.

Lasmiditan ameliorates serotonergic itch in mice: Possible involvement of 5-HT1F receptors.

Previously, some allergic conditions involving pruritus have been linked to migraine, raising the possibility that migraine and itching may be governed by similar underlying mechanisms. We aimed to investigate the efficacy of Lasmiditan, a highly selective agonist of the5-hydroxytryptamine 1F (5-HT1F) receptor and a recently approved medication for the treatment of migraine headaches, in ameliorating serotonergic itching. Forty animals were employed in the present study (n = 40). Eight animals were randomly assigned to each of the following study groups (n = 8, in each group): (1) "Normal Saline": This group was given intradermal injections of normal saline (2) "5-HT": The animals were injected with intradermal 5-HT, which was used to induce itching. (3) "Lasmiditan 0.3", "Lasmiditan 1", and "Lasmiditan 3" groups: injected with 5-HT as well as intraperitoneal Lasmiditan at different dose levels (0.3, 1, and 3mg/kg, respectively). Scratching behavior was recorded for 60min, and the skin tissue of three mice was sampled at the end of the behavioral experiment to assess the levels of TLR-4, IL-31, 5-HT1F receptor, CGRP & TRPV4. In the present study, we found that Lasmiditan when administered at 1mg/kg effectively reduced serotonin-induced itching compared to the "5-HT" group (P < 0.0001). Following the administration of Lasmiditan (1mg/kg), the expression levels of the 5-HT1F receptor significantly increased (P < 0.01). Further, the levels of TLR-4, IL-31, CGRP & TRPV4 were substantially reduced upon the administration of Lasmiditan (1mg/kg). We found that Lasmiditan is effective in reducing serotonergic itch in mice through its interaction with the 5-HT1F receptor in the skin tissue of mice.

Treatment patterns of patients with migraine eligible for anti-CGRP pathway monoclonal antibodies.

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. 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. 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. 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.

Lack of association between TRPV1 gene polymorphisms and risk of migraine chronification: a case-control study and meta-analysis.

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. 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. 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. 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.

Visual Field Defects and Retinal Nerve Fiber Layer Thickness in Migraine Patients: A Study From a Tertiary Care Center in India.

Background This study aimed to analyze the visual field changes and retinal nerve fiber layer (RNFL) thickness during the headache phase of migraine attacks among migraine patients compared with controls. Methodology A prospective, case-control study was conducted at a tertiary care center in Palakkad, Kerala from January 2022 to August 2023. This study included 50 migraine patients and 50 age/gender-matched controls. Adults aged 20-40 years with a more than three-year history of migraine were included in this study and those who had systemic or ocular pathologies were excluded. All 100 subjects underwent complete ocular examination, including full threshold 24-2 automated perimetry for visual field analysis and optical coherence tomography for analyzing RNFL thickness. Statistical analysis was done using SPSS Statistics Version 25 (IBM Corp., Armonk, NY, USA). Results In this study, the average age for cases was 29.24 ± 5.10 years, and for controls was 30.12 ± 6.20 years. Gender distribution was identical between cases and controls with 29 (58%) females and 21 (42%) males. Among the 50 migraine patients, 22 (44%) had generalized, while 28 (56%) had localized field defects during the headache phase of migraine attacks. There was a statistically significant (p < 0.001) difference in superior quadrant RNFL thickness between cases (114.08 ± 12.25) and controls. Conclusions We found that RNFL thinning in the superior quadrant and non-specific localized visual field changes occur during migraine attacks. We conducted this study in a tertiary care center as very few studies in our country have revealed visual field changes during migraine headache attacks.

Migraine Causality in Alpha-1 Antitrypsin Deficiency

Alpha1-antitrypsin (A1AT) is an anti-inflammatory mediator with antiprotease activity associated with anti-inflammatory and immunomodulatory effects in various inflammatory conditions. A1AT deficiency (A1ATD) has been associated with various hyperinflammatory diseases, such as lung disease (emphysema and bronchiectasis), liver disease (chronic hepatitis, cirrhosis, and hepatoma), and skin diseases (panniculitis). Migraine with aura is one of the common migraine subtypes associated with neuroimmunologic activation and neuroinflammation which is associated with cortical spreading depression and glial hyperinflammation in etioradiopathogenesis, and the main mechanisms explained so far are hyperinflammation of pro-inflammatory mediators, sensitivity of trigeminal nerve fibers and pain-conjugated glial cells activation. In this case report, a causative perspective of migraine with aura and A1ATD was presented through etioradiopathogenetics mechanisms that show the central reflections of systemic hyperinflammatory processes, and the importance of peripheral hyperinflammatory conditions in migraine etiology was examined.

Average steps per day as marker of treatment response with anti-CGRP mAbs in adults with chronic migraine: a pilot study

Physical activity can worsen migraine, leading to reduced activity levels in adults with chronic migraine. This study investigated the change in average steps per day, as a surrogate marker of physical activity, in adults with chronic migraine successfully treated with monoclonal antibodies against calcitonin gene-related peptide or its receptor. Data were obtained from adults with chronic migraine, who were classified as responders to preventive treatment with monoclonal antibodies. The primary endpoint was the difference in a mean number of steps per day between the 3 months prior to treatment initiation and the first 3 months after treatment initiation. The secondary endpoint was the correlation between the change in steps per day and the change in monthly migraine days. Twenty-two (20 females) participants with a median age of 48.5 years were enrolled. The median number of steps per day increased from 4421 at baseline to 5241 after treatment (P = 0.039). We found a positive correlation between the increase in steps per day and the treatment response (P = 0.013). In conclusion, an increase in physical activity, based on steps per day, positively correlated with treatment response to monoclonal antibodies. Automatically registered daily step count data might be used to monitor physical activity as a response to preventive treatment in adults with chronic migraine.

Use of rimegepant as an alternative to triptans in migraine treatment

Introduction and aim of study: Migraine is a chronic neurological disorder that is considered one of the leading causes of disability worldwide. Increasing evidence indicates that the calcitonin gene-related peptide (CGRP), a neuropeptide released during trigeminal nerve activation, plays a major role in pathophysiology and serves as an important therapeutic target. Rimegepant is an antagonist for the receptor of this peptide and an alternative to the commonly used triptans. Materials and Methods: Two databases, Pubmed and Medline, were searched using the terms "rimegepant" and "migraine." Results: By reducing the severity and frequency of migraine attacks, rimegepant significantly improves patients' daily functioning and quality of life. A single 75 mg dose of rimegepant provided better efficacy than placebo in the acute treatment of migraine. Two hours after dosing, significantly more patients in the rimegepant group than in the placebo group reported pain relief (59.3% vs. 43.3%). Rimegepant was also effective in the long term when taken every other day for preventive treatment of migraine and/or as needed for acute migraine treatment. When used, rimegepant was well tolerated in both acute and preventive migraine treatment. The most common adverse events included nasopharyngitis, nausea, urinary tract infection, and upper respiratory tract infection. Conclusions: Rimegepant is an effective drug for treating migraine attacks, offering quick and long-lasting pain relief with a favorable safety profile, especially for patients with contraindications to triptans. Therefore, rimegepant represents a valuable alternative for patients who do not respond adequately to other available migraine therapies.

“It’s just part of who I am…” Living with chronic headache: voices from the CHESS trial, a qualitative study

BackgroundBetween 2015 and 2019 the Chronic Headache Education and Self-management Study (CHESS) developed and tested a supportive self-management approach that aimed to improve outcomes for people with chronic migraine or chronic tension type headache with/without episodic migraine. However, a paucity of qualitative research which explored the lived experiences of people with chronic headache was evidenced. In response, we undertook to explore the experiences of living with chronic headaches of people who participated in the CHESS study.MethodsWe adopted qualitative methodologies, inviting participants in the CHESS study to participate in semi-structured interviews. In phase 1 (feasibility study), a thematic analysis was conducted. In phase 2 (main CHESS trial), interviews were informed by topic guides developed from our learning from the phase 1 interviews. Pen portrait methodology and thematic analysis was employed allowing us to explore the data longitudinally.ResultsPhase 1, 15 interviews (10 female) age range 29 to 69 years (median 47 years) revealed the complexities of living with chronic headache. Six overarching themes were identified including the emotional impact and the nature of their headaches. Phase 2, included 66 interviews (26 participants; median age group 50s (range 20s-60s); 20 females. 14 were interviewed at three points in time (baseline, 4 and 12 months) Through an iterative process four overlapping categories of headache impact emerged from the data and were agreed: i) ‘I will not let headaches rule my life’; ii) ‘Headaches rule my life’; iii) ‘Headaches out of control—something needs to change’; and iv) ‘Headaches controlled—not ruling my life’. One of these categories was assigned to each pen portrait at each timepoint.The remaining 12 participants were interviewed at two time points during a year; pen portraits were again produced. Analysis revealed that the headache impact categories developed above held true in this sample also providing some validation of the categories.ConclusionsThese data give an insight into the complexities of living with chronic headache. Chronic headache is unpredictable, permeating all aspects of an individual’s life; even when an individual feels that their headache is controlled and not interfering, this situation can rapidly change. It shows us that more work needs to be done both medically and societally to help people living with this often-hidden condition.Trial registrationISRCTN79708100

Open label experience of repeated OnabotulinumtoxinA injections towards the sphenopalatine ganglion in patients with chronic cluster headache and chronic migraine.

A novel technique for injection of OnabotulinumtoxinA (BTA) towards the sphenopalatine ganglion (SPG) has shown promise in refractory chronic migraine (CM) and chronic cluster headache (CCH). Open label safety and efficacy data are presented here. Patients with refractory CM or CCH who had received at least one injection and completed headache diaries were included. Efficacy was defined as ≥50% reduction in moderate-to-severe headache days for CM, or ≥50% reduction in attack frequency for CCH, at weeks five to eight. Over 261 injections, there were 123 adverse events (AE), of which one was serious. Most (93%) AEs were mild and all were transient. The 50% response to one injection was 81% for CM and 69% for CCH. The response gradually reduced over subsequent months for CM but stayed between 55% and 67% for CCH. Repeated injections were beneficial. Injections resulted in improvement for both groups and was maintained with repeated injections. Repeat injection after three months may be beneficial in CM. Adverse events were not uncommon, but universally transient, presumably as a result of the mechanism of action of BTA. Repeated BTA injection towards the SPG could be an effective treatment for refractory CM and CCH. Larger, randomised, placebo-controlled trials are required.

Systematic review and meta-analysis of Neck Disability Index and Numeric Pain Rating Scale in patients with migraine and tension-type headache.

The present study aimed to assess the burden of neck pain in adults with migraine and tension-type headache (TTH), utilizing the Neck Disability Index (NDI) and Numeric Pain Rating Scale (NPRS). A systematic literature search was conducted on PubMed and Embase to identify observational studies assessing NDI and NPRS in populations with migraine or TTH. The screening of articles was independently performed by two investigators (HMA and ZA). Pooled mean estimates were calculated through random-effects meta-analysis. The I2 statistic assessed between-study heterogeneity, and meta-regression further explored heterogeneity factors. Thirty-three clinic-based studies met the inclusion criteria. For participants with migraine, the pooled mean NDI score was 16.2 (95% confidence interval (CI) = 13.2-19.2, I2 = 99%). Additionally, the mean NDI was 5.5 (95% CI = 4.11-6.8, p < 0.001) scores higher in participants with chronic compared to episodic migraine. The pooled mean NDI score for participants with TTH was 13.7 (95% CI = 4.9-22.4, I2 = 99%). In addition, the meta-analysis revealed a mean NPRS score of 5.7 (95% CI = 5.1-6.2, I2 = 95%) across all participants with migraine. This systematic review and meta-analysis shows a greater degree of neck pain-related disability in migraine compared to TTH. Nevertheless, the generalizability of these findings is constrained by methodological variations identified in the current literature.

Safety of Triptans in Patients Who Have or Are at High Risk for Cardiovascular Disease: A Target Trial Emulation

ObjectiveTo evaluate the safety of triptans in migraine patients with cardiovascular disease or elevated cardiovascular risk. Patients and MethodsWe retrieved data from a multistate US-based health system (January 2000 to August 2022) on adults with migraine and confirmed cardiovascular/cerebrovascular disease, or at least two cardiovascular risk factors. We compared the effect of triptans to nontriptan treatments on major adverse cardiovascular events (MACE) and its components at 60 days of starting treatments. We emulated a target trial and used propensity score matching for analysis. ResultsThe 3518 patients in the triptan group were matched to the 3518 patients in the nontriptan group (median age, 55 years; 80.60% female). At 60 days, 52 patients (1.48%) in the triptan group had MACE, compared with 13 patients (0.37%) in the nontriptan group (relative risk [RR], 4.00; 95% CI, 2.24 to 7.14). Patients treated with triptans also had significantly higher risk of nonfatal myocardial infarction (15 patients (0.43%) vs 0 patients (0.00%)); heart failure (RR, 4.50; 95% CI, 1.91 to 10.61); and nonfatal stroke (RR, 8.00; 95% CI, 1.00 to 63.96). Five patients (0.14%) in each group died. The findings were consistent when analyses were restricted to sumatriptan, oral administration of triptan, patients with chronic migraine, history of cardiovascular disease, or history of cerebrovascular disease. ConclusionTriptans likely increase the risk of MACE; however, the incidence of MACE remains low in migraine patients with cardiovascular disease or elevated cardiovascular risk. Trial RegistrationTreatments of Migraine With Triptans in Individuals With Elevated Cardiovascular Risk and in Pregnant Women. ClinicalTrials.gov Identifier: NCT05854992 (https://classic.clinicaltrials.gov/ct2/show/NCT05854992)

Meningeal lymphatic vessel dysfunction driven by CGRP signaling causes migraine-like pain in mice.

Migraines are a type of headache that occur with other neurological symptoms, but the pathophysiology remains unclear. In this issue of the JCI, Nelson-Maney and authors used constitutive and inducible knockouts of the CGRP receptor components, elegantly demonstrating an essential function of CGRP in modulating meningeal lymphatic vessels (MLVs) in migraine. CGRP was shown to induce rearrangement of membrane-bound gap junction proteins in MLVs, resulting in a reduced CSF flux into cervical lymph nodes. The authors also provided evidence of a primary role for CGRP in modulating neuro-immune function. Finally, by showing that blocking CGRP signaling in MLVs attenuated pain behavior associated with acute migraine in rodents, the authors provided a target for pharmacological blockade of CGRP in relation to primary headache disorders.

The migraine epidemic among medical students: a call for action.

Migraine is characterized by recurrent headaches of moderate-to-severe intensity and poses a significant challenge for medical students. This is a narrative literature review using PubMed and Scopus databases. This study examines how common migraine is in this group and suggests working together to address how it affects students' well-being and chances of succeeding as a medical professional in the future. Early diagnosis by licensed medical specialists is essential for effective management of migraine. To address this, the authors propose a multifaceted strategy. By including direct education on migraines in medical school curricula, future doctors will be better prepared to treat patients with comparable problems and manage their own migraines. Students with migraines can also benefit greatly from creating a supportive learning environment through staff training, accommodating academic policies, and providing easily available healthcare resources. In addition, this technology may be helpful. Apps for relaxation and migraine tracking can help students better manage their condition. Long-term success requires cooperation among all parties. By promoting cooperation among medical schools, student associations, healthcare practitioners, and governmental organizations, the authors can raise public awareness of migraine, make pertinent resources easier to access, and create evidence-based solutions specially designed to meet the needs of medical students who experience migraine. In the end, putting student well-being first and working together to put these solutions into practice can enable aspiring doctors to succeed at both personal and professional levels.