Cephalalgia最新文献

{"title":"Decoding PACAP signaling: Splice variants, pathways and designer drugs.","authors":"Zoe Tasma, Debbie L Hay","doi":"10.1177/03331024251363560","DOIUrl":"https://doi.org/10.1177/03331024251363560","url":null,"abstract":"<p><p>The neuropeptides pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) play roles in vasodilation, the immune response and neuronal signaling, with recent links to headache disorders. This association has resulted in considerable interest in targeting this family of peptides and their receptors for drug development, and, notably, an anti-PACAP antibody has reported clinical efficacy in reducing migraine frequency. The PACAP/VIP ligands act at G protein-coupled receptors (GPCRs). PAC₁, VPAC₁ and VPAC₂ are the officially-recognized canonical receptors. Each of these has the potential to generate receptor variants through exon splicing. These variants may exhibit altered function, significantly increasing the diversity of PACAP-responsive receptors. In addition to these canonical receptors, PACAP is proposed to activate other unrelated receptors, GPR55 and MRGPRX2. Altogether, any of these canonical and proposed receptors may mediate the biological actions of PACAP, including migraine-relevant behaviors. However, we have a limited understanding of how these receptors function, such as their capacity to activate downstream signaling, the cellular and subcellular location of that signaling, and whether accessory protein interactions may alter these responses, especially in migraine-relevant contexts. The complex nature of the PACAP/VIP system therefore provides not only numerous considerations for target design and validation, but also unique opportunities for \"designer\" drugs. This narrative review provides an overview of the complex PACAP/VIP system, exploring peptide, receptor and downstream signaling behaviors that may be potential targets for the treatment of headache disorders and beyond.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 8","pages":"3331024251363560"},"PeriodicalIF":4.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Invisible burdens: Gender-specific associations between migraine and work-family conflict: Insights from the SMILE project - a cohort study.","authors":"Ido Peles, Shaked Sharvit, Yana Mechnik Steen, Michal Gordon, Victor Novack, Ronit Waismel-Manor, Gal Ifergane","doi":"10.1177/03331024251352533","DOIUrl":"10.1177/03331024251352533","url":null,"abstract":"<p><p>BackgroundMigraine, a neurovascular disorder that affects quality of life, with peak prevalence during individuals' most productive working years. Work-family conflict (WFC), a well-documented source of stress, occurs when work and family responsibilities interfere with each other. While migraine has been associated with occupational impairment, its association with WFC remains underexplored. The present study examines the association between migraine diagnosis, severity and WFC, stratified by gender.MethodsThis study analyzed data from the SMILE cohort, a subset of the Negev Migraine Cohort. Participants with and without migraine were recruited and completed a structured questionnaire assessing WFC. The main exposures were migraine diagnosis and severity, measured using the Migraine Disability Assessment (MIDAS) score. The primary outcome was WFC. Covariates included sociodemographic characteristics, employment factors, and psychological distress (Depression, Anxiety and Stress Scale - 21 Items (DASS-21)). Statistical analyses involved multivariable gamma generalized linear mode regression models and quantile regression to examine associations, adjust for potential confounders and effect modification by gender.ResultsIn total, 675 migraine patients and 232 non-migraine participants were included in the study; 80.6% of migraine patients were female. Severe disability (MIDAS score ≥21) was reported by 65.0% of migraine patients, with employment rates of 89.2% for females and 93.1% for males. Migraine patients worked longer hours per week (median 40.0 vs. 36.0 hours for females, and 48.0 vs. 42.0 hours for males), and were more likely to work over 42 hours per week (18.2% vs. 7.0% for females and 32.8% vs. 8.7% for males, standardized mean difference = 0.487). Migraine diagnosis was associated with higher Work To Family and Family To Work strain-based conflict scores among males (β = 0.43, 95% confidence interval = 0.06-0.78, <i>p</i> = 0.03 and β = 0.35, 95% 95% confidence interval = 0.03-0.66, <i>p</i> = 0.04, respectively); however, no statistically significant associations were observed among female. Higher migraine severity (MIDAS) was correlated with greater WFC, with the effect more pronounced at higher levels of migraine disability and more strongly associated with men (<i>p</i> < 0.01 for all).ConclusionsMigraine is associated with higher WFC, especially in strain-based domains, with a stronger effect in men. Greater migraine severity further amplifies this conflict. These findings emphasize the need for workplace and clinical strategies to support migraine patients in managing work-life balance.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 8","pages":"3331024251352533"},"PeriodicalIF":4.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in cortical morphometry between persistent post-traumatic headache, migraine and healthy controls.","authors":"Rune Häckert Christensen, Haidar Muhsen Al-Khazali, Messoud Ashina, Nina Vashchenko, Rogelio Dominguez-Moreno, Daniel Tolnai, Håkan Ashina","doi":"10.1177/03331024251362830","DOIUrl":"https://doi.org/10.1177/03331024251362830","url":null,"abstract":"<p><p>BackgroundPersistent post-traumatic headache (PTH) is a prevalent and disabling neurological disorder, often attributed to mild traumatic brain injury and resembling migraine in clinical features. The underlying cortical morphometric changes and their relevance to persistent PTH remain unclear.MethodsThis cross-sectional magnetic resonance imaging (MRI) investigation enrolled 103 adults with persistent PTH, 296 with migraine and 155 healthy controls (HC), to undergo structural MRI at 3T. Cortical surface area, thickness and volume were evaluated in FreeSurfer. The analyses applied cluster-determining thresholds of <i>p</i> < 0.001 and cluster-wise thresholds of <i>p</i> < 0.05, adjusted for age, sex and total intracranial volume.ResultsParticipants with persistent PTH exhibited larger surface area in the right anterior and posterior cingulate cortex (<i>p</i>_cluster = 0.003), as well as the right superior parietal cortex/postcentral gyrus, compared to HC (<i>p</i>_cluster < 0.035). No morphometric differences were observed between participants with persistent PTH and migraine (including subgroups: episodic, chronic, with aura without aura).ConclusionsThese findings reveal morphometric alterations in persistent PTH, specifically within pain processing regions of the mid-cingulate and somatosensory cortex. Similar changes have been reported in migraine, suggesting a shared neurobiological substrate. These enlargements might reflect adaptations to recurrent nociceptive stimuli that sustain persistent PTH.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 8","pages":"3331024251362830"},"PeriodicalIF":4.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic cluster headache is a rare disease: Implications for diagnosis, treatment and public health.","authors":"Hsiangkuo Yuan, Jan Hoffmann, Elena Ruiz de la Torre, Michael J Marmura, Mario F P Peres","doi":"10.1177/03331024251369752","DOIUrl":"https://doi.org/10.1177/03331024251369752","url":null,"abstract":"<p><p>Cluster headache (CH) is a rare and painful primary headache disorder characterized by severe unilateral pain and cranial autonomic symptoms. This perspective examines the epidemiological evidence supporting the classification of chronic cluster headache (CCH) as a rare disease, noting a prevalence of CH of approximately 124 per 100,000 individuals, with only 3.5-13.7% manifesting CCH. This prevalence meets criteria established by both the US Food and Drug Administration and European Medicines Agency for rare disease designation. The rarity of CCH creates substantial clinical and research challenges, including prolonged diagnostic delays, limited research funding and a dearth of approved treatments. The economic burden is particularly notable, with annual costs exceeding €20,000 per patient. Addressing these challenges requires a coordinated approach focusing on increased research funding, enhanced policy advocacy, improved diagnostic training and the development of comprehensive disease registries to advance both patient care and scientific understanding of this devastating neurological condition.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 8","pages":"3331024251369752"},"PeriodicalIF":4.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reviewing the complex relationship between circadian rhythms and cluster headache.","authors":"Mark Burish, Seung Ae Kim, Caroline Ran, Seung-Hee Yoo, Mi Ji Lee, Andrea Carmine Belin","doi":"10.1177/03331024251365858","DOIUrl":"10.1177/03331024251365858","url":null,"abstract":"<p><p>Cluster headache attacks display uniquely rhythmic patterns in their manifestations. Multiple international studies have shown circadian and even circannual timing of attacks, although we do not yet fully understand the effects of culture, sleep, chronotype, seasonal changes, temperature or inter-individual changes over time. Multiple cluster headache treatments alter the core circadian oscillator, although they affect the oscillator differently and are not well understood. Multiple small genetic studies have shown core circadian gene variants to be cluster headache susceptibility genes, whereas larger genetic studies have not shown core circadian gene variants but have also not documented the presence or absence of circadian rhythmicity. In this narrative review, we describe the multi-level circadian features of cluster headache and propose future circadian directions, including a clinical definition of circadian attacks, a potential animal model of circadian headache and study design changes to incorporate circadian features into larger genetic studies.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 8","pages":"3331024251365858"},"PeriodicalIF":4.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144844726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to Wasserman et al.: Elucidating the \"Triggers\" versus \"Maintenance\" in burning mouth syndrome/oral dysaesthetic and perceptual disorder.","authors":"Takayuki Suga, Trang Thi Huyen Tu, Daniela Adamo, Akira Toyofuku","doi":"10.1177/03331024251369533","DOIUrl":"10.1177/03331024251369533","url":null,"abstract":"","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 8","pages":"3331024251369533"},"PeriodicalIF":4.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is PACAP the next big thing in migraine therapy?","authors":"Lars Edvinsson","doi":"10.1177/03331024251368748","DOIUrl":"10.1177/03331024251368748","url":null,"abstract":"","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 8","pages":"3331024251368748"},"PeriodicalIF":4.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term safety, efficacy and functional outcomes of atogepant for the preventive treatment of migraine.","authors":"Sait Ashina, Messoud Ashina, Dagny Holle-Lee, Cristina Tassorelli, Soo-Jin Cho, Molly Yizeng He, Rosa De Abreu Ferreira, Pranav Gandhi, Jonathan H Smith, Kimberly Pfleeger, Joel M Trugman","doi":"10.1177/03331024251365206","DOIUrl":"10.1177/03331024251365206","url":null,"abstract":"<p><p>AimLong-term data for oral calcitonin gene-related peptide receptor antagonist, atogepant, in episodic migraine (EM) has been reported. This is the first report on one-year outcomes in participants with chronic migraine (CM) and in the EM population with prior preventive treatment failures. Here, we report the long-term safety, tolerability, efficacy and functional outcomes of one-year preventive treatment of EM or CM with atogepant.MethodsThis is an interim analysis of an ongoing, open-label, multicenter, 156-week, safety extension study that enrolled completers from phase 3 PROGRESS and ELEVATE trials. The participants completing week 52 or early termination were evaluated. Eligible adults with at least a one-year history of migraine, with either CM (PROGRESS) or EM who previously had inadequate response to two to four classes of conventional oral preventive treatments (ELEVATE). All participants received atogepant 60 mg once daily. The primary outcome was safety and tolerability of atogepant. Efficacy and functional outcomes were prespecified exploratory analyses.ResultsOf 596 participants, 595 (PROGRESS, n = 325; ELEVATE, n = 270) were treated and included in the safety population and 524 (PROGRESS, n = 284; ELEVATE, n = 240) were included in the modified intent-to-treat population. In this interim analysis, mean duration of atogepant exposure was 496.5 days. Treatment-emergent adverse events (TEAEs) occurred in 79.0% of participants; most were mild/moderate and not related to atogepant. Common TEAEs (≥5%) included COVID-19 (28.7%), nasopharyngitis (10.9%) and constipation (8.2%). TEAEs leading to discontinuation occurred in 5.9% of participants. One death attributed to asphyxia by housefire was observed. Other serious TEAEs occurred in 5.5% of participants and none were related to atogepant. Alanine aminotransferase and/or aspartate aminotransferase ≥3× upper limit of normal occurred in two participants; neither met Hy's law criteria. Improvements in efficacy and functional outcomes from lead-in study baseline were observed at weeks 13-16 in this open-label study and were consistent through 48 and 52 weeks, respectively.ConclusionsOverall safety results were consistent with the known safety profile of atogepant and the drug was well-tolerated over the course of the study. No new safety signals were identified. Improvements in efficacy and functional outcomes were consistent during the study.Trial RegistrationClinicalTrials.gov identifier: NCT04686136.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 8","pages":"3331024251365206"},"PeriodicalIF":4.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The psychometric properties of an e-headache diary in migraine.","authors":"Nancy van Veelen, Nadine Pelzer, Britt W H van der Arend, Natasha Waslam, Daphne S van Casteren, Erik J Giltay, Gisela M Terwindt","doi":"10.1177/03331024251359222","DOIUrl":"https://doi.org/10.1177/03331024251359222","url":null,"abstract":"<p><p>ObjectiveTo evaluate the psychometric characteristics of a previously validated electronic headache diary with automated algorithm for the purpose of identifying migraine days.MethodsThe psychometric properties of 13 variables in this e-diary were analyzed using item response theory (IRT) in migraine patients from the Leiden Headache Center. The included items were headache presence, duration, unilaterality, severity, pulsating, aggravation by physical activity, visual aura, aura duration, nausea, vomiting, photophobia or phonophobia and triptan usage. The added value to the end-diagnosis of an already validated migraine day of the individual items was assessed. A generalized partial credit model was used to evaluate the items. A discriminative value α ≥ 1.70 indicated an excellent discrimination.ResultsIn total 1418 migraine patients were analyzed with a mean age of 43 years, 89% were women and 38% reported aura symptomatology. All items demonstrated excellent discriminative value [α: 1.82-54.1], except for aura duration [α:0.86], which was moderate. Cronbach's alpha was 0.91. The answers options of headache duration, photophobia, phonophobia, nausea and vomiting did not reach the probability threshold of 0.5.ConclusionsThe items in this e-headache diary demonstrated good overall psychometric performance, although certain items, particularly aura-related and multi-categorical items, may benefit from category merging or further refinement.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 8","pages":"3331024251359222"},"PeriodicalIF":4.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute confusional migraine: Proposal for inclusion in the International Classification of Headache Disorders - 4th edition (ICHD-4).","authors":"Karen Dos Santos Ferreira, Ana Miriam Velly","doi":"10.1177/03331024251370305","DOIUrl":"10.1177/03331024251370305","url":null,"abstract":"","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 8","pages":"3331024251370305"},"PeriodicalIF":4.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}