Journal of Headache and Pain最新文献

{"title":"Impact of semaglutide introduction on the use of triptans: an interrupted-time series.","authors":"Noémie Roland, Heidi Sonne, Lanfranco Pellesi, Maja Bramming, Lise Gehrt Cardél, Anton Pottegård, Helene Kildegaard","doi":"10.1186/s10194-026-02462-4","DOIUrl":"10.1186/s10194-026-02462-4","url":null,"abstract":"<p><strong>Background: </strong>Emerging evidence suggests that glucagon-like peptide-1 receptor agonist (GLP-1RA) may be associated with reduced migraine burden. We aimed to evaluate whether semaglutide for weight management initiation is associated with changes in triptan consumption.</p><p><strong>Methods: </strong>We conducted a nationwide interrupted time series analysis using Danish health registers. All adults initiating semaglutide between December 2022 and December 2024 were included. The first dispensing date served as the index date, establishing a 24-month baseline and a 12-month follow-up period. The primary outcome was monthly triptan consumption (defined daily doses (DDD)/10,000 individuals). Analyses were conducted for new and prevalent triptan users, and stratified by sex, age group, and prior use of prophylactic antimigraine medication.</p><p><strong>Findings: </strong>During the study period, 189,392 individuals initiated semaglutide (68% females, median age 50 years). Before initiation, triptan use increased over time; after initiation, this trend reversed, showing a decline of -13 DDD/month/10,000 (95% CI: -25 to -1.3), corresponding to a 7% relative reduction at 12 months (RR 0.93; 0.88-0.97). This decrease primarily reflected a reduction in DDD consumption among prevalent users (RR 0.86; 0.82-0.90) rather than a change in monthly rates of new users. A sex-specific effect was observed, with female users demonstrating an 8% reduction (RR 0.92; 0.88-0.97) and males showing no statistically significant change. The largest reductions occurred in individuals aged 18-35 years (RR 0.86; 0.78-0.94) and previous users of prophylactic antimigraine medications (RR 0.88; 0.82-0.94).</p><p><strong>Conclusions: </strong>Weight-loss semaglutide initiation was associated with a modest, gradual reduction in triptan use, particularly among females and individuals with history of migraine.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"27 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13445726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148678828","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":"Genome-wide association susceptibility loci for cluster headache support a role for inflammation in the pathophysiology.","authors":"Caroline Ran, Clémence Deborgies Sanches, Julia Swedblom, Katrin Wellfelt, Alessandro Antoniazzi, Joseph Lloyd, Felicia Jennysdotter Olofsgård, Stefan Spulber, Elisabet Waldenlind, Maria Lantz, Anna Steinberg, Anna Sundholm, Christina Sjöstrand, Andrea Carmine Belin","doi":"10.1186/s10194-026-02485-x","DOIUrl":"10.1186/s10194-026-02485-x","url":null,"abstract":"<p><strong>Background: </strong>Recent genetic findings have broadened the perspectives of cluster headache pathophysiology. Genes identified by genome wide association studies are likely to be involved in the pathophysiological mechanisms underlying the disease. In this study, we performed validation and characterization of eight loci corresponding to nine genes identified in previous genome wide association studies.</p><p><strong>Methods: </strong>Genetic loci were validated by means of a case-control study using TaqMan genotyping in 671 individuals, and a meta-analysis using previously genotyped data. Pyrosequencing methylation analysis and reverse transcription quantitative PCR gene expression studies was performed in a subset of individuals with cluster headache and healthy controls.</p><p><strong>Results: </strong>Genetic associations were found with functional variants in two genes; FHL5 and MERTK. The minor allele of the FHL5 variant rs2273621 was associated with an increased risk of cluster headache in the genotyped samples (odds ratio = 1.42, P = 0.03) and in a meta-analysis (odds ratio = 1.29, confidence interval: 1.09-1.52), and the minor allele of the rs2230515 variant in MERTK was associated with lower risk in the meta-analysis (odds ratio = 0.69, confidence interval: 0.52-0.92). Methylation analysis further revealed altered methylation status of MERTK. Moreover, changes in relative gene expression were found for several candidate genes: a decrease in the mRNA expression of DUSP10 (P < 0.001), CAPN2 (P < 0.001), UFL1 (P < 0.001) and LRP1 (P = 0.007) in blood, and a decrease of CAPN2 (P < 0.001) as well as an increase in the mRNA expression of FTCDNL1/FONG (P = 0.004) in fibroblasts in CH vs. controls. Only two genes; PLCE1 and WNT2, could not be validated in the biological tissue studied; WNT2, possibly due to limited power, while PLCE1 was not expressed in the available tissue.</p><p><strong>Conclusions: </strong>These results confirm the validity of seven candidate genes for cluster headache identified through GWAS. Furthermore, five of the candidate genes are abundantly expressed in both immune and blood cells, converge functionally on inflammatory signalling pathways and suggest a potential role for inflammasomes in cluster headache.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"27 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13440057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148678894","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":"Headache-attributed burden among children and adolescents in Nepal: a national schools-based cross-sectional study.","authors":"Rajeev Ojha, Ragesh Karn, Bikram Prasad Gajurel, Reema Rajbhandari, Niraj Gautam, Bikash Deo, Aakarshan Timilsina, Anushka Adhikari, Ravi Raj Timasina, Gaurav Nepal, Derya Uludüz, Tayyar Şaşmaz, Bengü Nehir Buğdaycı Yalçın, Andreas Kattem Husøy, Timothy J Steiner","doi":"10.1186/s10194-026-02472-2","DOIUrl":"https://doi.org/10.1186/s10194-026-02472-2","url":null,"abstract":"<p><strong>Background: </strong>We recently published estimates of 1-year headache prevalence among children (6-11 years) and adolescents (12-17) in Nepal. Adjusted for age and gender, these were 83.9% for all headache, 39.5% for migraine, 31.7% for undifferentiated headache (UdH), 10.0% for tension-type headache (TTH), 0.3% for probable medication-overuse headache (pMOH) and 1.9% for other headache on ≥ 15 days/month (other H15+). Here we present estimates of attributed burden.</p><p><strong>Methods: </strong>We followed the Global Campaign's standardised protocol. In nine schools representative of the country, the child and adolescent versions of the structured HARDSHIP questionnaire were completed by pupils in class under supervision. Headache diagnoses followed ICHD-3, except for UdH, defined here as mild or moderate headache with usual duration < 1 h. Burden enquiries were in multiple domains, with timeframes of 4 weeks and 1 day, the latter based on reports of headache yesterday (HY).</p><p><strong>Results: </strong>There were 2,352 participants (1,040 children [44.2%]; 1,312 adolescents [55.8%]) from 2,360 eligible (participating proportion 99.7%). Symptom burden was expressed as moderate headache on an average of 2.9 days/4 weeks, lasting for 2.0 h. Mean proportion of time in ictal state (pTIS) was 1.0%, but much higher among those with pMOH (11.0%) or other H15+ (9.4%). Except for pMOH, only one third of headache episodes were medicated. Lost school time was 3% estimated from recall over the preceding 4 weeks, with similar time lost from other (social and leisure) activities. Actual absences from school yesterday because of HY were more (4.5%), suggesting losses were underestimated by recall, but, since recorded absences yesterday failed to capture absences on days preceding weekends or holidays, true losses might have been 5-6%. More than one fifth (21.7%) of parents lost time from their own work. Both emotional impact and quality-of-life (QoL) scores were sensitive to headache (and headache type), showing gradients of negative impact (pMOH and other H15+ > migraine > TTH and UdH).</p><p><strong>Conclusions: </strong>Symptom burden appeared to be relatively modest except for pMOH and H15+, but measures of impaired participation (including lost time from school), emotional impact and QoL all indicated material impact. Parents, teachers, health-care providers and policy makers should be aware of this.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"27 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13483492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794085","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":"Acupuncture modulates migraine-related neural and neuroendocrine regulatory pathways.","authors":"Hao Huang, Yu Tao, Yuan Zhang, Fangting Luo, Huimin Hu, Zitong Huang, Weiwei Lu, Yufang Sun, Xin Jin, Jingwei Li, Jin Tao","doi":"10.1186/s10194-026-02481-1","DOIUrl":"10.1186/s10194-026-02481-1","url":null,"abstract":"<p><strong>Background: </strong>Migraine is a common, disabling neurological disorder driven by neurovascular and neuroinflammatory mechanisms. Although calcitonin gene-related peptide (CGRP)-targeted and serotonergic drugs have improved treatment, many patients still respond inadequately or experience side effects. Acupuncture is widely used as a non-pharmacological alternative, yet its mechanistic basis lacks systematic integration.</p><p><strong>Principal findings: </strong>Accumulating clinical and experimental evidence suggest that acupuncture effectively reduces migraine frequency, pain intensity, and disability, with sustained preventive benefits. Neuroimaging studies reveal that acupuncture modulates key brain regions and networks involved in pain perception, emotional regulation, and descending pain control, including the default mode, salience, and sensorimotor networks. At the molecular level, preclinical evidence indicates that acupuncture may modulate CGRP signaling, serotonergic neurotransmission, neuronal excitability, and inflammatory pathways, thereby attenuating central sensitization and neuroimmune activation. Emerging evidence further suggests that acupuncture affects hypothalamic metabolic pathways involving glucagon-like peptide-1 (GLP-1) and orexin. Given that these neuropeptides are also implicated in the pathogenesis of migraines, this finding may offer a potential mechanistic perspective on how acupuncture alleviates this condition. These findings support a multi-level regulatory role of acupuncture that extends beyond symptomatic analgesia.</p><p><strong>Conclusion: </strong>Acupuncture is supported as a preventive therapy for select migraine patients, but mechanistic evidence remains heterogeneous and mostly associative or preclinical. While a multilevel framework might link acupuncture-evoked brain, molecular, and homeostatic changes, direct validation in migraine is needed. Future work should prioritize standardized interventions, credible sham controls, longitudinal neuroimaging, and integrated molecular readouts to elucidate response mechanisms and predictive biomarkers.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"27 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13584362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982694","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":"Integrative genetic analysis identifies shared regulation of DNA methylation and gene expression in migraine risk.","authors":"Ammarah Ghaffar, Dale R Nyholt","doi":"10.1186/s10194-026-02469-x","DOIUrl":"10.1186/s10194-026-02469-x","url":null,"abstract":"<p><strong>Background: </strong>Migraine affects approximately 14% of adults, but the molecular mechanisms underlying susceptibility remain incompletely understood. Although genome-wide association studies (GWAS) have identified many migraine risk loci, translating these associations into biological insight remains challenging. Environmental and physiological migraine triggers, including hormones, diet and stress, may act partly through epigenetic mechanisms such as DNA methylation. Because many migraine risk variants are non-coding and may influence disease through regulatory effects, integrating genetic association data with DNA methylation and gene expression may help refine migraine-associated loci into candidate molecular mechanisms.</p><p><strong>Methods: </strong>We performed a novel methylome-wide association study (meWAS) of migraine, imputing genetically regulated DNA methylation at 86,518 cytosine-phosphate-guanine (CpG) sites using GWAS summary statistics derived from 102,084 migraine cases and 771,257 controls of European ancestry. We then linked DNA methylation signals to imputed gene expression using transcriptome-wide association study (TWAS) evidence across 49 Genotype-Tissue Expression tissues. Bayesian colocalisation analyses were used to prioritise CpGs and genes supported by shared causal variants with migraine risk, and to map shared regulatory signals between methylation and expression quantitative trait loci.</p><p><strong>Results: </strong>We identified 258 migraine-associated CpG sites after Bonferroni correction (P < 5.78 × 10^-7), of which 177 colocalised with migraine GWAS variants (PP4 > 0.5) and mapped to 69 independent genomic loci, including 58 established and 11 putative novel loci. Integration with TWAS evidence prioritised 199 genes (candidate-set Bonferroni-corrected TWAS P < 7.84 × 10^-5) near these CpG sites, including 91 genes with evidence of colocalisation with migraine GWAS variants. Further colocalisation between methylation and expression quantitative trait signals mapped shared regulatory signals to 120 CpGs and 78 genes across 40 independent genomic loci, comprising 32 established and eight putative novel migraine risk loci. Protein-protein interaction analysis showed modest but significant network enrichment, with local modules implicating signalling organisation, mitochondrial function, oxidative stress, and related regulatory processes.</p><p><strong>Conclusions: </strong>These findings show that migraine susceptibility is partly shaped by shared genetic regulation of DNA methylation and gene expression. By refining GWAS loci into candidate genes and molecular signals, this integrative multi-omic framework highlights distributed molecular pathways relevant to neuronal and vascular responsiveness and identifies candidates for future functional characterisation.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"27 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13508431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818462","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":"Headache-attributed burden among children and adolescents in Georgia: estimates from a national cross-sectional schools-based study.","authors":"Nana Nino Tatishvili, Zaza Katsarava, Teona Shatirishvili, Tamar Kipiani, Tinatin Giuashvili, Mariam Lomsianidze, Aleksandre Kotetishvili, Anano Kvernadze, Irakli Tugushi, Salome Maghlakelidze, Vera Nemsadze, Ana Bedoshvili, Tamar Bitskinashvili, Giorgi Sakvarelidze, Derya Uludüz, Tayyar Şaşmaz, Deniz Erdal, Andreas Kattem Husøy, Timothy J Steiner","doi":"10.1186/s10194-026-02451-7","DOIUrl":"https://doi.org/10.1186/s10194-026-02451-7","url":null,"abstract":"<p><strong>Background: </strong>We recently published an account of headache prevalence among children (6-11 years) and adolescents (12-17) in Georgia, reporting an age- and gender-adjusted 1-year estimate of 66.3% for all headache. With undifferentiated headache (UdH) defined as mild or moderate headache lasting < 1 h, age- and gender-adjusted prevalence of migraine was 22.2%, of tension-type headache (TTH) 9.5%, of UdH 30.2%, of probable medication-overuse headache (pMOH) 0.5%, and of other headache on ≥ 15 days/month (other H15+) 3.6%. Here, using the same definition of UdH, we present data on attributed burden, collected contemporaneously from the same participants. The study was within the worldwide programme of cross-sectional schools-based studies undertaken by the Global Campaign against Headache.</p><p><strong>Methods: </strong>We used the Global Campaign's standardized protocol, selecting schools representative of the country. The child and adolescent versions of the structured Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire, translated into Georgian language, were completed by pupils under supervision in class. Headache diagnoses followed International Classification of Headache Disorders, edition 3 (ICHD-3), except for UdH, which was defined as mild or moderate headache lasting < 1 h. Burden enquiry was in multiple domains, including symptom burden, impaired participation and quality of life (QoL), with timeframes of 4 weeks and 1 day (the latter based on headache yesterday [HY]).</p><p><strong>Results: </strong>Symptom burden was evidenced by mean headache frequency of 4.3 days/4 weeks, duration 1.6 h, proportion of time in ictal state 1.5% and intensity 1.7 (mild to moderate). Of episodic headaches, migraine was the most frequent, longest lasting and most intense. Pupils with pMOH reported headache on 78.9% of all days. Except for pMOH, fewer than half of headache days were medicated. Headache was blamed for 0.7 days/4 weeks of missed school (3.5% of 20 days), although only 1.5% of the 1,910 pupils with headache in the last year were absent yesterday because of HY (this analysis could not capture lost days immediately preceding weekends or holidays, so underestimated by at least 20%). Almost one in five parents (18.3%) of children lost time from their own work because of their child's headache, but only 4.5% of parents of adolescents. Emotional impact and QoL scores both showed gradation across headache types (pMOH and other H15 + worse than migraine worse than TTH and UdH).</p><p><strong>Conclusions: </strong>Headache among children and adolescents in Georgia is associated with individual- and population-level burdens that measurably and adversely affect health, wellbeing, education and participation in leisure activities. These findings are available to inform national education and health policies.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"27 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13474696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148760627","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":"Twelve-months prospective real-world assessment of effectiveness and safety of eptinezumab in migraine patients difficult-to-treat and naïve to CGRP monoclonal antibodies: results of the French FHU INOVPAIN registry.","authors":"S Ferrao-Malheiro, R Fabre, T Jiacomini, M Lanteri-Minet","doi":"10.1186/s10194-026-02428-6","DOIUrl":"10.1186/s10194-026-02428-6","url":null,"abstract":"<p><strong>Background: </strong>Randomized clinical trials have demonstrated the efficacy and safety of eptinezumab. The aim of this study was to evaluate the effectiveness and safety of eptinezumab in a real-world setting among patients with difficult-to-treat migraine in France.</p><p><strong>Methods: </strong>This is a one year-prospective real-word study including all consecutive adult patients from the Federation Hospitalo-Universitaire InovPain registry who received intravenous eptinezumab 100 mg.</p><p><strong>Results: </strong>Three hundred and two patients (83.8% female / mean age of 48.0 ± 13.9 years) were included. Patients had at least 8 monthly migraine days, had failed at least 3 previous prophylactic treatments across amitryptiline, betablockers, botulinum toxin, candesartan, and topiramate and were Calcitonin Gene Related Peptide monoclonal antibodies naïve. Among them, 184 patients (60.9%) had chronic migraine and 118 (39.1%) had episodic migraine, whereas 229 patients (75.8%) presented a medication overuse. Regarding the primary endpoint, 50% responder rate at month 3, month 6, and month 12 was 35.4% (107/302), 39.0% (96/246), and 45.7% (63/138), respectively. ≥30% responder rate at month 3, month 6, and month 12 was 48.7% (147/302), 56.1% (138/246), and 63.0% (87/138), respectively. ≥75% responder rates at M3, M6, and M12 was 10.9% (33/302), 15.4% (38/246), and 23.2% (32/138), respectively. The effectiveness of eptinezumab was confirmed by significant changes in the values of all patient reported outcome measures at all assessment time points compared with baseline, demonstrating improvement in functional impact (Headache Impact Test-6), emotional impact (Hospital Anxiety Depression Scale), interictal burden (Migraine Interictal Burden Scale-4), and quality of life (Euro Qol-5 Dimensions descriptive system and visual analogue scale). According to Patient Global Impression of Change, the proportions of patients reporting being \"much improved\" or \"very much improved\" were 41.9% at month 3, 54.8% at month 6 and 74.4% at month 12. Overall, effectiveness appeared similar in episodic migraine and chronic migraine except at month12, where rates of 50% and 75% response were significantly higher in the chronic migraine (50% response: 53.8% vs. 34.5%, p = 0.025; 75% response: 30% vs. 13.8%, p = 0.026). Adverse events were uncommon and mostly mild, transient, and self-limited with few expected hypersensitivity reactions.</p><p><strong>Conclusions: </strong>This French real-word study confirms the effectiveness and safety of eptinezumab in difficult-to-treat patients with migraine who and have failed non-specific preventive migraine treatments and are naïve to Calcitonin Gene Related Peptide monoclonal antibodies.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"27 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13422293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148630769","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":"Exploratory Ising model network analysis of cluster headache: mapping conditional associations across symptoms, triggers, and pain localization.","authors":"Mansoureh Togha, Omid Kohandel Gargari, Fariborz Khorvash, Mohsen Hoseinnezhad, Elham Jafari, Arya Derakhshesh, Shiva Rahimi, Vahid Shaygannejad, Zhale Salami, Mahdi Badiee-Gavarti, Reza Shokrani Foroushani, Sheida Shaafi, Faraidoon Haghdoost","doi":"10.1186/s10194-026-02474-0","DOIUrl":"10.1186/s10194-026-02474-0","url":null,"abstract":"<p><strong>Background: </strong>Cluster headache (CH) is a rare and disabling primary headache disorder characterized by severe unilateral pain and cranial autonomic symptoms. Although its diagnostic criteria are well defined, the conditional relationships among symptoms, reported triggers, and pain locations are not well characterized. Network analysis may provide an exploratory framework for examining these co-occurrence patterns.</p><p><strong>Objective: </strong>To characterize conditional associations among symptoms, reported triggers, and headache regions in patients with CH using Ising model-based network analysis and to evaluate the stability of the estimated edge and centrality patterns.</p><p><strong>Methods: </strong>A cross-sectional analysis was conducted using data from the Iranian National Cluster Headache Registry. Binary variables indicating the presence or absence of symptoms, reported triggers, and headache regions were analyzed. Separate symptom, trigger, and headache-region networks, together with an integrated network, were estimated using EBIC-regularized Ising models (γ = 0.25) in R (v4.4.3). Strength and bridge-strength point estimates were calculated. Nonparametric and case-dropping bootstrap procedures (1,000-3,000 iterations) were used to assess edge-weight accuracy and correlation stability (CS); CS coefficients below 0.25 were considered insufficient for robust interpretation of centrality rankings.</p><p><strong>Results: </strong>Data from 321 patients were analyzed. In the symptom network, the largest estimated positive edges included epiphora-runny nose (1.80) and miosis-runny nose (1.05); epiphora and miosis had the highest strength point estimates, but strength centrality did not meet the prespecified stability threshold (CS = 0.206). The trigger network was unstable (edge CS = 0.05; strength CS = 0.00), and trigger edge and centrality rankings were therefore not interpreted. The headache-region network showed stronger stability (edge CS = 0.748; strength CS = 0.361), with a positive neck-occipital association (2.16) and a negative lower-jaw-cheek association (-2.31). In the integrated network, edge stability was moderate (CS = 0.439), whereas strength centrality remained below the interpretation threshold (CS = 0.206); bridge-strength estimates, including runny nose (2.17), were treated as exploratory.</p><p><strong>Conclusion: </strong>Ising network analysis identified conditional co-occurrence patterns among CH features, with the most robust findings arising from the headache-region network. Symptom centrality, trigger-network estimates, and integrated centrality and bridge rankings require cautious interpretation because of limited stability. These cross-sectional findings are hypothesis-generating and support validation in larger and longitudinal datasets; they do not establish causal mechanisms or clinically actionable treatment targets.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"27 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13430735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669766","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":"Temporal neural dynamics patterns in episodic and chronic migraine: a magnetoencephalography study.","authors":"Cunxin Lin, Dong Qiu, Pan Liao, Geyu Liu, Jie Liang, Zhonghua Xiong, Xiaoshuang Li, Chenyang Duan, Zhe Wang, Zhi Guo, Yongxiang Zhang, Zhaoli Ge, Xin Liu, Yuanxiang Li, Tianshuang Gao, Mantian Zhang, Jia-Hong Gao, Bingjiang Lyu, Yonggang Wang","doi":"10.1186/s10194-026-02466-0","DOIUrl":"10.1186/s10194-026-02466-0","url":null,"abstract":"<p><strong>Background: </strong>Chronic migraine (CM) severely affects patients' work and daily life, imposing a significant economic burden. However, the underlying neural mechanisms of migraine chronification remain unclear. This study aimed to characterize temporal neural dynamics patterns of migraine via magnetoencephalography (MEG) combined with dynamic network mode (DyNeMo), providing further neuroimaging evidence for migraine chronification.</p><p><strong>Methods: </strong>This cross-sectional study recruited patients with episodic migraine (EM), CM, and healthy controls (HC). MEG data were acquired during resting and somatosensory stimulation states. The DyNeMo model was applied to source-reconstructed MEG data to quantify temporal neural dynamics metrics, including mean lifetime, mean interval, switching rate and fractional occupancy. Permutation-based analysis of covariance (ANCOVA) with Bonferroni correction and Spearman correlation with false discovery rate (FDR) correction were applied.</p><p><strong>Results: </strong>Six distinct brain modes were identified: visual network (VN), anterior and posterior default mode networks (aDMN/pDMN), right and left sensorimotor networks (rSMN/lSMN), and auditory network (AN). During resting state, EM showed prolonged mean lifetime and decreased switching rate of the VN vs. HC; CM showed increased switching rate of the VN vs. EM; CM showed prolonged mean lifetime and decreased switching rate of the AN vs. HC. During somatosensory stimulation state, both EM and CM showed prolonged mean lifetime and decreased switching rate of the AN vs. HC. In CM patients, longer duration of disease was correlated with shorter mean lifetime and higher switching rate of the AN during somatosensory stimulation state.</p><p><strong>Conclusions: </strong>This study identifies distinct alterations in the temporal dynamics of VN and AN in EM and CM. Abnormalities in AN were observed during both resting and somatosensory stimulation states, while disease duration in CM was associated with altered temporal metrics of the AN. These cross-sectional findings support the involvement of altered sensory and cross-modal network processing in migraine and warrant longitudinal validation.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"27 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13625361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080986","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 immune cell gene targets and their relationship to psychiatric disorders.","authors":"Xin Mo, Dongren Sun, Fangfang Li, Danqi Wang, Yunjiao Deng, Yiwei Liao, Xiaosu Yang, Haiting Zhao","doi":"10.1186/s10194-026-02465-1","DOIUrl":"10.1186/s10194-026-02465-1","url":null,"abstract":"<p><strong>Background: </strong>Migraine frequently co-occurs with psychiatric disorders, yet the immunogenetic mechanisms linking these conditions remain largely unexplored.</p><p><strong>Methods: </strong>Using cis-eQTL data from 28 immune cell subtypes (1,925 donors) and GWAS summary statistics for migraine and five psychiatric disorders, we performed single-cell transcriptome-wide Mendelian randomization, Bayesian colocalization, genetic correlation, and cross-disease pleiotropy analyses. Independent replication was performed using external datasets.</p><p><strong>Results: </strong>Migraine and its subtypes showed significant positive genetic correlations with all five psychiatric disorders (rg = 0.39-0.73). We identified 83 immune cell gene targets for migraine, 13 for migraine with aura, and 19 for migraine without aura. Among these, 6 targets showed shared associations with anxiety and 1 with depression. Three prioritized genes-HLA-A, CDK2AP1, and TTC24-demonstrated cross-disease pleiotropic effects. Notably, HLA-A in cDC1 exhibited discordant pleiotropy (protective for migraine with aura, risk for depression), with known drug-gene interactions involving antiepileptics and tricyclic antidepressants.</p><p><strong>Conclusions: </strong>These findings suggest that immune cell-specific genes, particularly HLA-A, CDK2AP1, and TTC24, may bridge migraine and psychiatric disorders, offering potential candidates for further investigation into shared immunogenetic mechanisms.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"27 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13464352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712685","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}