Journal of Headache and Pain最新文献

{"title":"Inhibition of the METTL3/m⁶A/miR-34a-5p axis suppresses trigeminovascular activation in nitroglycerin-induced migraine via the Wnt/β-catenin pathway.","authors":"Hui Zhang, Minming Shao, Feng Zhang, Caiyan He, Jiabi Li, Shengdong He","doi":"10.1186/s10194-025-02144-7","DOIUrl":"10.1186/s10194-025-02144-7","url":null,"abstract":"<p><strong>Background: </strong>Neuroinflammation is a key driver of migraine pathogenesis, particularly by promoting neuronal sensitization. METTL3-mediated m⁶A methylation has emerged as a critical epigenetic regulator in neuroinflammatory responses. This study aims to investigate the role of METTL3 in migraine, focusing on its m⁶A-dependent regulatory mechanisms.</p><p><strong>Methods: </strong>A rat migraine model was induced via chronic intermittent nitroglycerin administration. Behavioral tests assessed migraine-like symptoms. Protein and RNA levels of METTL3, miR-34a-5p, and downstream targets were analyzed using Western blot, qPCR, ELISA, and immunofluorescence. The interaction among METTL3, miR-34a-5p, and Wnt1 was validated through Co-IP, RIP, and luciferase reporter assays.</p><p><strong>Results: </strong>METTL3 expression was significantly upregulated in the trigeminal ganglia of migraine rats. Knockdown of METTL3 reduced trigeminovascular system (TGVS) activation and alleviated migraine symptoms. Mechanistically, METTL3 enhanced miR-34a-5p expression via m⁶A modification, leading to suppression of the Wnt1/β-catenin pathway. Overexpression of miR-34a-5p further aggravated migraine-related responses by inhibiting Wnt1 signaling.</p><p><strong>Conclusion: </strong>METTL3 contributes to migraine pathogenesis through m⁶A-dependent upregulation of miR-34a-5p, which suppresses the Wnt1/β-catenin axis and promotes TGVS activation. Targeting this pathway may offer new therapeutic avenues for migraine.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"197"},"PeriodicalIF":7.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of machine learning in migraine classification: a call for study design standardization and global collaboration.","authors":"Igor Petrušić, Roberta Messina, Lanfranco Pellesi, David Garcia Azorin, Chia-Chun Chiang, Adriana Della Pietra, Woo-Seok Ha, Alejandro Labastida-Ramirez, Dilara Onan, Raffaele Ornello, Bianca Raffaelli, Eloisa Rubio-Beltran, Ruth Ruscheweyh, Claudio Tana, Doga Vuralli, Marta Waliszewska-Prosół, Wei Wang, William David Wells-Gatnik, Paolo Martelletti, Alberto Raggi","doi":"10.1186/s10194-025-02134-9","DOIUrl":"10.1186/s10194-025-02134-9","url":null,"abstract":"<p><p>Migraine is a complex neurological disorder with diverse clinical phenotypes and a multifaceted pathophysiology, which poses substantial challenges for accurate diagnosis, subtype differentiation, and biomarker discovery. Machine learning (ML) techniques have emerged as promising tools for classifying migraine patients and uncovering the underlying neurobiological mechanisms that differentiate migraine types and subtypes. This systematic review identifies current ML classification models for migraine types and subtypes, evaluating the quality, reproducibility, and clinical utility of published studies. The findings demonstrate that current ML models, particularly support vector machines and linear discriminant analysis, can accurately classify migraine patients based on structural and functional neuroimaging features with accuracies ranging from 75 to 98%. However, quality assessment revealed significant methodological heterogeneity across studies, including inconsistent reporting of model performance, insufficient patient phenotyping, small and imbalanced datasets, and limited external validation. These limitations hinder the global generalizability and reproducibility of these studies. We propose a roadmap for future research emphasizing well-characterized clinical subgrouping, standardized data acquisition and feature engineering protocols, transparency in model development and reporting, and collaborative multicentric designs to enable large-scale validation. Furthermore, this review stresses the importance of incorporating real-world phenotypic data, such as treatment response, comorbidities, and digital phenotyping metrics, to enrich ML models and support the transition toward precision medicine in migraine care. Ultimately, this review highlights the urgent need for methodological rigor in migraine ML classification studies to bridge the gap between experimental success and clinical applicability.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"200"},"PeriodicalIF":7.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profiling the real-world migraine patient: public health insights from sociodemographic, lifestyle, and clinical data in the Italian National Migraine Registry (I-GRAINE).","authors":"Piero Barbanti, Giulia Fiorentini, Cecilia Camarda, Massimo Autunno, Francesca Pistoia, Cinzia Aurilia, Florindo d'Onofrio, Gabriella Egeo, Antonio Carnevale, Stefano Caproni, Alberto Doretti, Alessandra Cherchi, Roberto De Simone, Maurizio Zucco, Steno Rinalduzzi, Bruno Colombo, Massimo Filippi, Simone Quintana, Marco Russo, Alfonso Coppola, Rosario Grugno, Marco Bartolini, Giovanna Viticchi, Renata Rao, Maria Albanese, Fabrizio Vernieri, Licia Grazzi, Micaela Robotti, Alfonsina Di Summa, Marco Aguggia, Monica Laura Bandettini Di Poggio, Cinzia Finocchi, Rossana Terlizzi, Mattia Sansone, Francesca Gragnani, Pietro Querzani, Francesco Perini, Paolo Solla, Valentina Favoni, Ludovica Ferrau, Gennaro Saporito, Elisabetta Iannaccone, Carlo Colosimo, Stefano Messina, Laura Di Clemente, Francesca Cortese, Paola Scatena, Domenico Cosenza, Nicoletta Brunelli, Giacomo Querzola, Annalisa Gai, Sara Cazzulo, Francesco Tazza, Martina Guarinoni, Tommaso Ercoli, Sofia Tavani, Bianca Orlando, Francesco Bono, Pietro Antonio Bruno, Stefania Proietti, Stefano Bonassi, Carlo Tomino, Annamaria Porreca, Paola Torelli, Sabina Cevoli","doi":"10.1186/s10194-025-02146-5","DOIUrl":"10.1186/s10194-025-02146-5","url":null,"abstract":"<p><strong>Background: </strong>Although migraine attacks have been precisely characterized over the years - with significant advances in pathophysiology and treatment - the comprehensive identity of the migraine patient remains poorly defined. Real-world data capturing the full sociodemographic and clinical spectrum of individuals with migraine is still limited. The Italian National Migraine Registry (I-GRAINE) was established to address this gap by systematically collecting data on individuals with migraine across Italy's public healthcare system.</p><p><strong>Methods: </strong>I-GRAINE is an ongoing, nationwide, multicenter, prospective registry involving 43 publicly funded headache centers. Since 19/04/2021, patients diagnosed with episodic migraine (EM) or chronic migraine (CM) have been systematically enrolled. Data were collected through face-to-face interviews conducted by trained neurologists using a dedicated electronic platform. Information included sociodemographic and lifestyle factors, comorbidities, and detailed clinical characteristics. We aimed to define the patient profile, explore the broad clinical phenotype, and compare EM and CM subgroups.</p><p><strong>Results: </strong>As of 02/05/2025, 1,630 patients had been enrolled (81.7% EM, 18.3% CM), predominantly female (85.4%), mean age 45.7 years, normal BMI (23.2 kg/m²), and high education level. Over 70% were physically inactive, and 32.2% reported sleep disturbances. Headache was typically unilateral (69.1%), pulsating (64.0%), and lasted > 24 h (57.1%). Frequently reported non-ICHD-3 symptoms included osmophobia (41.5%), allodynia (40.5%), dopaminergic symptoms (37.2%), cephalalgiaphobia (34.0%), and dizziness (16.9%). ≥ 1 comorbidity was present in 41.2% of patients. Compared to those with EM, CM patients had higher BMI (24.0 vs. 23.0, p < 0.001), greater sleep disturbances (39.1% vs. 30.6%, p = 0.006), earlier onset (16.5 vs. 17.7 years, p = 0.032), more severe pain (NRS: 8.1 vs. 7.5, p < 0.001), and higher prevalence of medication overuse (58.3% vs. 14.5%, p < 0.001), dopaminergic symptoms (45.1% vs. 35.4%, p = 0.002), allodynia (47.5% vs. 38.9%, p = 0.009), and cephalalgiaphobia (41.4% vs. 32.3%, p = 0.004). Disability was also greater (MIDAS: 76.3 vs. 41.9; HIT-6: 64.3 vs. 61.2; both p < 0.001).</p><p><strong>Conclusions: </strong>The typical patient attending Italian headache centers is a 45-year-old, normal-weight, well-educated, employed woman, often physically inactive, affected by sleep disturbances, and experiencing an average of 9.8 migraine days/month. I-GRAINE identifies migraine symptoms that may represent endophenotypes and distinct patterns associated with CM, offering valuable real-world insights to inform personalized care, research, and health policy.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"199"},"PeriodicalIF":7.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissecting immune cell-specific genetics in migraine: a multi-omics framework for target discovery and therapeutic prioritization.","authors":"Yanggang Hong, Yuze Mi, Feng Chen, Yirong Wang, Jiajun Li, Zhendi Shu","doi":"10.1186/s10194-025-02132-x","DOIUrl":"10.1186/s10194-025-02132-x","url":null,"abstract":"<p><strong>Background: </strong>Migraine is a highly prevalent neurological disorder with complex pathophysiology and limited treatment efficacy. Emerging evidence suggests immune cell involvement in migraine, but the specific regulatory mechanisms remain unclear. This study aimed to identify immune cell-type-specific genetic drivers of migraine and prioritize potential therapeutic targets.</p><p><strong>Methods: </strong>We conducted a Mendelian randomization (MR) analysis integrating single-cell expression quantitative trait loci (sc-eQTL) data from 14 immune cell types with large-scale genome-wide association studies (GWAS) of migraine. Colocalization analysis, protein-protein interaction (PPI) networks, linkage disequilibrium score regression (LDSC), phenome-wide association studies (PheWAS), and drug repurposing databases were utilized to validate findings and assess therapeutic potential and safety.</p><p><strong>Results: </strong>We identified 25 immune cell-specific eGenes causally associated with migraine, including CDC42, NELFCD, HOXB3, HAX1, and FHL3. Several genes, such as CDC42 and HAX1, were implicated across multiple immune cell types. Subtype-specific analyses revealed differential gene effects in migraine with aura (MA) and without aura (MO). Genetic correlation and pleiotropy analyses linked eGenes to comorbid traits such as depression, gastrointestinal disorders, and blood pressure. PheWAS suggested minimal adverse associations for prioritized genes like GINM1 and TMA7. Drug repurposing identified FDA-approved agents, including hydroxychloroquine sulfate (NELFCD) and bazedoxifene (CDC42), as potential migraine therapies.</p><p><strong>Conclusion: </strong>This study reveals immune cell-specific genetic contributors to migraine and highlights druggable targets for therapeutic development. Integrating sc-eQTL with multi-omics and pharmacological data provides a novel framework for precision medicine in migraine.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"195"},"PeriodicalIF":7.9,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CREB-KIF1A-CGRP-positive feedback loop drives central sensitization in chronic migraine.","authors":"Wei Jiang, Peng Yu, Yan-Min Shi, Li-Xi Zhang, Meng-Tan Cai, Yu Yang, Ming Dong","doi":"10.1186/s10194-025-02147-4","DOIUrl":"10.1186/s10194-025-02147-4","url":null,"abstract":"<p><strong>Background: </strong>Chronic migraine (CM), defined as ≥ 15 monthly headache days and often involving central sensitization, is a complex neurological disorder. While calcitonin gene-related peptide (CGRP) is a key migraine target, its upstream regulation remains unclear. Kinesin family member 1A (KIF1A), which is essential for axonal transport, is transcriptionally regulated by cAMP response element-binding protein (CREB). The aim of this study was to elucidate the role of the CREB-KIF1A-CGRP signaling axis in the pathogenesis of migraine.</p><p><strong>Methods: </strong>CMs were generated in mice through repeated nitroglycerin (NTG) injections, and thermal and mechanical allodynia was evaluated behaviorally. Molecular changes in the spinal trigeminal nucleus caudalis (SP5C) and Neuro-2a cells were examined using immunoblotting, qPCR, and immunofluorescence. Mechanistic studies included chromatin immunoprecipitation and dual-luciferase assays to verify the CREB-mediated transcriptional regulation of Kif1a, coimmunoprecipitation (Co-IP) to assess KIF1A-CGRP interactions, and synaptosomal CGRP analysis following Kif1a knockdown. Pharmacological interventions included Forskolin (a CREB agonist), 666 - 15 (a CREB inhibitor), Kif1a knockdown/overexpression, and Olcegepant (a CGRP receptor antagonist).</p><p><strong>Results: </strong>NTG treatment activated the CREB-KIF1A-CGRP pathway and induced migraine-like hypersensitivity. Forskolin-induced CREB activation upregulated KIF1A and CGRP expression, whereas inhibition of CREB expression by 666 - 15 reversed these effects. ChIP and luciferase assays confirmed the direct binding of CREB to the Kif1a promoter. Kif1a knockdown reduced p-CREB, CGRP, and c-Fos levels in SP5C tissue and Neuro-2a cells, alleviating behavioral hypersensitivity. Co-IP showed that KIF1A physically associated with CGRP, and synaptosome analysis revealed decreased CGRP in vesicles after Kif1a knockdown. Overexpression of Kif1a increased CGRP levels, but this effect was reversed by age. CGRP receptor blockade also inhibited Forskolin-induced activation of p-CREB, c-Fos, and KIF1A. These findings support a CGRP-dependent positive feedback loop within the CREB-KIF1A-CGRP axis that drives migraine pathogenesis.</p><p><strong>Conclusions: </strong>These findings reveal a CREB-KIF1A-CGRP positive feedback loop that drives migraine-like hypersensitivity. CREB directly regulates KIF1A transcription, which in turn promotes CGRP expression and signaling. Disruption of this axis effectively attenuated migraine-associated behaviors and molecular responses, highlighting potential therapeutic targets for the treatment of CM.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"194"},"PeriodicalIF":7.9,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural oscillation mechanisms of repetitive subconcussive impacts: a network study of microstate-specific cross-frequency coupling.","authors":"He Yida, Li Huanhuan, Li Xiang, Fu Zhenghao, Chen Lida, Gao Lijie, Gao Junfeng, Song Jian","doi":"10.1186/s10194-025-02135-8","DOIUrl":"10.1186/s10194-025-02135-8","url":null,"abstract":"<p><strong>Background: </strong>Repetitive subconcussive impacts are linked to headache pathophysiology, yet the role of electroencephalography (EEG) microstates and cross-frequency coupling in repetitive subconcussive (SC) neural alterations remains unclear. This study investigated microstate-specific cross-frequency coupling network (MCFCN) abnormalities in SC-exposed individuals to uncover mechanisms underlying headache vulnerability.</p><p><strong>Methods: </strong>Resting-state EEG was recorded from 16 experienced male parachuters aged 18-25 years (SC group) and 16 demographically matched healthy male controls of the same age range (HC group). Microstate analysis (four canonical classes: A-D) and cross-frequency coupling (CFC) interactions (n: m) phase synchronization index, PSI) were computed to construct the MCFCNs. The MCFCNs were evaluated using machine learning (LightGBM classifier) to discriminate between the two groups, with key features identified by SHAP values and corrected for multiple comparisons.</p><p><strong>Results: </strong>SC-exposed individuals exhibited MCFCN disruptions in large-scale networks. Notably, reduced delta/theta to alpha/beta coupling was observed in microstates A, C, and D, except for an increase in delta-band coupling from the default mode network (DMN) to the frontoparietal network (FPN) in microstate A. These alterations involved emotional-motor integration, attentional control, and self-referential processing. LightGBM models achieved significant group discrimination, with SHAP analysis highlighting theta-DMN, beta-SMN, and delta-LIM as critical nodes.</p><p><strong>Conclusions: </strong>SC exposure induces MCFCNs abnormalities resembling central pain syndromes, even in the absence of overt symptoms. These findings suggest that interactions within MCFCNs may serve as potential early biomarkers for headache vulnerability and chronicity, warranting further exploration in longitudinal studies and targeted neurointerventions.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"193"},"PeriodicalIF":7.9,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence in headache medicine: between automation and the doctor-patient relationship. A systematic review.","authors":"Christian Espinoza-Vinces, Marlon Cantillo Martínez, Ainhoa Atorrasagasti-Villar, María Del Mar Gimeno Rodríguez, David Ezpeleta, Pablo Irimia","doi":"10.1186/s10194-025-02143-8","DOIUrl":"10.1186/s10194-025-02143-8","url":null,"abstract":"<p><strong>Background: </strong>Headache disorders, particularly migraine, are highly prevalent, but often remain underdiagnosed and undertreated. Artificial intelligence (AI) offers promising applications in diagnosis, prediction of attacks, analysis of neuroimaging and neurophysiology data, and treatment selection. Its use in headache medicine raises ethical, regulatory, and clinical questions, including its impact on the doctor-patient relationship.</p><p><strong>Methods: </strong>A systematic literature search was conducted on April 10, 2025, across PubMed, Cochrane Library, Scopus, Web of Science, and DOAJ, following PRISMA guidelines. Two reviewers independently applied strict inclusion criteria to select studies published from 2000 to 2025 in either English or Spanish. Risk of bias was assessed using validated tools tailored to study design, including the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2), Prediction Model Risk of Bias Assessment Tool (PROBAST), Newcastle-Ottawa Scale (NOS), and Appraisal Tool for Cross-Sectional Studies (AXIS).</p><p><strong>Results: </strong>A total of 76 studies were included in the qualitative synthesis. The analysis covered AI methodologies, clinical applications, patient perspectives, and ethical implications. AI tools have shown potential to improve diagnostic accuracy, headache subtype classification, and prediction of treatment response, and may help reduce the administrative burden in clinical practice. Emerging technologies such as digital twins, wearable biomarker monitoring, and synthetic data generation support personalized approaches and may reshape clinical research. However, significant challenges remain. These include data quality, model interpretability, algorithmic bias, privacy concerns, and regulatory gaps. Moreover, the evidence base is still developing, with expectations often exceeding the strength of available clinical data. Many studies present methodological limitations due to small sample sizes, selection bias, and lack of external validation, which limit their generalizability to real-world settings. Finally, concerns about depersonalization and transparency affect patient trust in AI, reinforcing the need for both human oversight and a patient-centered approach.</p><p><strong>Conclusions: </strong>AI holds promise for improving headache care, but evidence supporting its clinical utility is still limited. Integration into practice must be rigorously validated, ethically guided, and carefully designed to prevent depersonalization. Human oversight remains essential as AI should complement, not replace, clinical judgment.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"192"},"PeriodicalIF":7.9,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Migraine triggers and lifestyle modifications: an assessment of patients' awareness and the role of healthcare providers in patient education.","authors":"Alaa Elmazny, Rehab Magdy, Mona Hussein, Ahmed Yehia Ismaeel, Ahmed Essmat, Karim Essam Elbeltagy, Shrouk Mohamed Mohamed Hussein, Nahed Shaban Hassan, Nada Mamdouh Elbehiry, Wesam Osama, Hebatallah N Abdelazeem, Haidy Elshebawy","doi":"10.1186/s10194-025-02107-y","DOIUrl":"10.1186/s10194-025-02107-y","url":null,"abstract":"<p><strong>Background and objectives: </strong>Lifestyle modifications and coping with migraine triggers have a crucial role in migraine management. This study aimed to assess the knowledge of patients with migraine about triggers, managing strategies for these triggers, and the counselling provided by physicians regarding these topics.</p><p><strong>Methods: </strong>A cross-sectional study was conducted on individuals with a confirmed diagnosis of migraine through an online survey to assess their knowledge of common migraine triggers, whether the healthcare provider had discussed migraine triggers or recommended lifestyle modifications, and strategies followed to manage migraine triggers.</p><p><strong>Results: </strong>Five hundred fifteen patients with migraines responded to the survey, with a median age of thirty-one years. Only 43% thought they had sufficient knowledge about migraine triggers. Stress got the highest awareness level (93.4%), followed by sleep-related issues. About 40% of participants were aware of certain food triggers. While 63.1% of participants said their physicians had addressed lifestyle changes to help reduce migraines, only 28.3% reported actively managing their migraine triggers. The most frequently discussed aspect was sleep hygiene improvements (78.1%), followed by stress management techniques (68.7%), and dietary modifications (59.8%). Regarding the approaches applied for migraine management, following a consistent sleep schedule, stress management techniques, and a specific diet were reported by 54.0%, 49. 5%, and 34.0%, respectively. Moreover, only 18% keep a detailed migraine diary to track their triggers.</p><p><strong>Conclusion: </strong>Addressing migraine triggers and coping strategies should be integrated into migraine management to reduce reliance on medications and activate personalized plans to optimize outcomes.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"189"},"PeriodicalIF":7.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the epigenetic modifications of the RONS-TRPA1-CGRP axis in migraine pathophysiology.","authors":"Michal Fila, Elzbieta Pawlowska, Jan Krekora, Maria Mitus-Kenig, Janusz Blasiak","doi":"10.1186/s10194-025-02114-z","DOIUrl":"10.1186/s10194-025-02114-z","url":null,"abstract":"<p><strong>Background: </strong>Epigenetic studies in migraine provided results on the occurrence or lack of epigenetic modifications of genes whose products are important in migraine pathogenesis. However, these studies focus on single genes without analyzing how epigenetic modifications can affect complex signaling pathways. This narrative/hypothesis review aims to provide information on how the reactive oxygen and nitrogen species (RONS)-transient receptor potential cation channel subfamily A member 1 (TRPA1)-calcitonin gene-related peptide (CGRP) axis functions, suggesting that its epigenetic modifications could be a significant factor in migraine pathophysiology.</p><p><strong>Main body: </strong>Oxidative stress is both a cause and a consequence of migraine, and reactive oxygen and nitrogen species (RONS), like other noxious stimuli, may activate the transient receptor potential cation channel subfamily A member 1 (TRPA1) to send pain signals. Methylation of the TRPA1 gene correlates with various pain states; however, the results of these studies are largely inconsistent. DNA methylation and the action of non-coding RNAs are important in the alternative RNA processing of the calcitonin-related polypeptide alpha (CALCA) gene and its transcript to produce calcitonin gene-related peptide (CGRP). The release of CGRP and substance P from trigeminal neuron terminals, mediated by TRPA1 activation and involving mitogen-activated protein kinase 1/2, is a primary mechanism driving migraine headaches. Epigenetic memory may be related to neural plasticity and migraine chronification. Therefore, the RONS-TRPA1-CGRP signaling pathways may be important in migraine pathogenesis, as demonstrated in experimental animals by the phenomenon of cortical spreading depolarization.</p><p><strong>Conclusion: </strong>The RONS-TRPA1-CGRP axis plays a significant role in the pathogenesis of migraine and other pain-related syndromes. Epigenetic modifications of the genes encoding the components of the antioxidant defense system, TRPA1 and CGRP, are crucial in migraine pathogenesis, prevention, and therapy. However, due to the sequence specificity of the axis, only non-coding RNAs can currently be considered for therapeutic intervention in migraine, targeting the epigenetic profile of the RONS-TRPA1-CGRP axis.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"191"},"PeriodicalIF":7.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A nomogram for the prediction of response to anti-CGRP mAbs: the CGRP score.","authors":"Marina Romozzi, Ammar Lokhandwala, Catello Vollono, David García-Azorín, Giulia Vigani, Francesco De Cesaris, Claudia Altamura, Fabrizio Vernieri, Paolo Calabresi, Sonia Di Tella, Luigi Francesco Iannone","doi":"10.1186/s10194-025-02138-5","DOIUrl":"10.1186/s10194-025-02138-5","url":null,"abstract":"","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"190"},"PeriodicalIF":7.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144956987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}