Journal of Headache and Pain最新文献

{"title":"Altered hypothalamic metabolism in chronic cluster headache patients measured with ¹H-MRS at ultra-high magnetic field.","authors":"Avneesh Jain, Anna Xiu Rørnes, Anne Farestveit, Maria Tunset Grinde, Axel Karl Gottfrid Nyman, Beathe Sitter, Tore Wergeland, Erling Tronvik, Guglielmo Genovese","doi":"10.1186/s10194-026-02446-4","DOIUrl":"10.1186/s10194-026-02446-4","url":null,"abstract":"<p><strong>Background: </strong>The hypothalamus is considered a central hub in the pathophysiology of cluster headache (CH), yet its neurochemical profile remains poorly understood. Proton magnetic resonance spectroscopy (¹H-MRS) offers a non-invasive tool for in vivo assessment of brain metabolites related to neuronal integrity and energy metabolism, but previous studies in CH have been restricted to conventional magnetic field scanner (≤ 3 T), which has resulted in limited metabolic information. Ultra-high field (7 T) MR scanners enhance ¹H-MRS with improved signal-to-noise ratio and separation of metabolite signals, providing more accurate and broader metabolic information, which may refine our understanding of hypothalamic dysfunction in chronic cluster headache (cCH). This study investigated whether patients with cCH exhibit altered hypothalamic metabolite concentrations compared with healthy volunteers (HVs).</p><p><strong>Methods: </strong>¹H-MRS at 7 T was performed in 10 cCH patients and 11 HVs to measure the neurochemical profile of the hypothalamus. Spectra were quantified with LCModel, yielding ratios of 9 metabolites relative to total creatine (tCr). Welch's unpaired t-tests were performed as a first-level exploratory analysis to compare metabolites between the two groups. Then, group differences in metabolite ratios were examined using analysis of covariance, with age and sex included as covariates to control for potential demographic effects.</p><p><strong>Results: </strong>Compared with HVs, cCH patients showed significantly reduced glutamate (Glu)/tCr (∼17%; p < 0.001) and N-acetyleaspartate (NAA)/tCr (∼10%; p = 0.048), with no other metabolite differences. After adjusting for covariates, a significant group effect was still observed for Glu/tCr (p = 0.0045), whereas no group difference was found for NAA/tCr (p = 0.079). Tissue composition within the voxel did not differ between groups, indicating that the observed metabolic differences were unlikely to be driven by partial-volume effects.</p><p><strong>Conclusions: </strong>This is the first study to characterize hypothalamic metabolism in cCH at 7 T. The observed reductions in Glu, together with a statistically less robust decrease in NAA, indicates hypothalamic neuronal involvement, possibly reflecting mitochondrial and energetic dysfunction. This ultrahigh-field finding extends previous results at conventional magnetic field intensities, offering more specific neurochemical evidence for hypothalamic involvement in cCH.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13339285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387642","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":"Trigeminovascular calcitonin gene-related peptide release and peripheral vascular responses in a mouse model of accelerated aging: Implications for migraine.","authors":"Linda Al-Hassany, Eloisa Rubio-Beltrán, Alejandro Labastida-Ramirez, Ingrid M Garrelds, A H Jan Danser, Anton J M Roks, Antoinette MaassenVanDenBrink","doi":"10.1186/s10194-026-02441-9","DOIUrl":"10.1186/s10194-026-02441-9","url":null,"abstract":"<p><strong>Objective: </strong>Understanding age-related changes in migraine is pivotal, considering the increasing global life expectancy. In addition, both aging and migraine are prominent cardiovascular risk factors. It remains unclear whether calcitonin gene-related peptide (CGRP) release changes with age across trigeminovascular components, and how this relates to peripheral responses to migraine-related vasodilatory molecules. The primary aim was to investigate age-related effects on CGRP release from the trigeminovascular system by studying a mouse model of combined accelerated neuronal and vascular aging, the DNA repair-deficient Ercc1^Δ/- mice. Second, we assessed the effects of aging on isolated coronary vasodilatory responses to CGRP and forskolin.</p><p><strong>Methods: </strong>Experiments were conducted using DNA repair-deficient Ercc1^Δ/-mice and their wild type controls. After sacrifice, the trigeminal nucleus caudalis (TNC), trigeminal ganglion (TG), and dura mater (DM) were isolated. Ex vivo KCl-induced CGRP release was measured, and CGRP release was compared between Ercc1^Δ/- and wild type mice. In a subset of mice, concentration-response curves to CGRP and forskolin were generated in isolated coronary arteries. The pEC₅₀ (negative log of the molar concentration of an agonist needed to reach half of its maximal effect) and E_max (maximum relaxation response) values were compared between both groups.</p><p><strong>Results: </strong>CGRP release (expressed as ratio compared to baseline release) of the DM was significantly lower in Ercc1^Δ/- (2.01 ± 0.24) versus wild type mice (3.22 ± 0.48) (P = 0.040). No differences were observed in CGRP release between Ercc1^Δ/-and wild type mice in the TNC (8.07 ± 1.15 versus 6.10 ± 0.57, P = 0.364) or the TG (4.84 ± 0.92 versus 4.41 ± 0.60, P = 0.838). In addition, there were no differences in pEC₅₀ and E_max values in response to CGRP and forskolin.</p><p><strong>Conclusion: </strong>Our findings suggest that aging is linked to reduced CGRP release of the DM, potentially partly explaining the reduction in migraine attacks in elderly. This decreased CGRP release is not accompanied by altered peripheral vascular reactivity to CGRP.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13340349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148382151","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":"Predictive factors of response to anti-CGRP pathway drugs in people with multiple sclerosis.","authors":"Viviana Nociti, Simone Cesarano, Marina Romozzi, Rocco Totaro, Maria Albanese, Alfonsina Casalena, Pietro Annovazzi, Roberta Fantozzi, Carla Tortorella, Marco Vercellino, Luigi Francesco Iannone, Giovanna De Luca, Valentina Tomassini, Massimiliano Di Filippo, Lorena Lorefice, Giorgia Teresa Maniscalco, Damiano Paolicelli, Federica Pinardi, Valentina Torri Clerici, Girolama Alessandra Marfia, Diego Centonze, Claudio Marcello Solaro, Claudio Gasperini, Paolo Calabresi, Massimiliano Mirabella, Catello Vollono, Eleonora Cocco, Francesca Pistoia","doi":"10.1186/s10194-026-02435-7","DOIUrl":"10.1186/s10194-026-02435-7","url":null,"abstract":"<p><strong>Background: </strong>Migraine is common in people with multiple sclerosis (PwMS) and substantially contributes to disability and impaired quality of life. Although (CGRP)-targeting therapies have reshaped migraine prevention, evidence on their use in PwMS remains scarce, particularly in people receiving concomitant disease-modifying therapies (DMTs).</p><p><strong>Methods: </strong>We retrospectively collected data from 17 Italian multiple sclerosis (MS) centers on adult PwMS with comorbid migraine treated with anti-CGRP monoclonal antibodies or gepants in addition to stable DMTs. Monthly headache days (MHDs) and total number of analgesics per month were compared between treatment initiation and last follow-up. MS activity was assessed through clinical relapses, Expanded Disability Status Scale (EDSS), and MRI findings. A ≥ 50% reduction in MHDs defined treatment response. Multivariate regression models were used to explore predictors of response to anti-CGRP therapies.</p><p><strong>Results: </strong>Fifty-four patients were included (46 women; mean age 42.3 years; 85% relapsing MS). Baseline MHDs averaged 19.87 ± 6.97 and declined to 11.40 ± 9.35 at follow-up (p < 0.001), with a parallel decrease in analgesic use (p < 0.001). Responder rate at the last follow-up was 53.7%. MS disease activity remained stable, with no significant changes in relapse rate, EDSS score, or MRI activity. Higher baseline headache burden was associated with greater reduction in MHDs (β=+0.685, p < 0.001), whereas longer MS duration predicted poorer response (OR1.43, 95%CI 1.06-1.92, p = 0.016). Mild adverse events occurred in four patients (7%), without treatment discontinuation.</p><p><strong>Conclusion: </strong>Anti-CGRP pathway therapies provided meaningful migraine improvement in PwMS while maintaining MS stability. MS disease duration and baseline headache frequency may influence therapeutic response to anti-CGRP drugs in PwMS.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13430695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148382124","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":"Profile of migraine patients in Middle East and North Africa (MENA) region: a multi-center study.","authors":"Mona Hussein, Jasem Al-Hashel, Derya Uludüz, Ahmed Allioueche, Yasmine Kamal, Mohammed Tahir Kurmanji, Diana Khedr, Aynur Ӧzge, Ahmed Dahshan, Hanaa Kedah, Emna Ellouz, Imen Ketata, Aussan Al-Athwari, Wael Alwahchi, Amina Chentouf, Najib Kissani, May M Fayez, Amr Hassan","doi":"10.1186/s10194-026-02424-w","DOIUrl":"10.1186/s10194-026-02424-w","url":null,"abstract":"<p><strong>Background: </strong>The Middle East and North Africa (MENA) region presents a unique demographic, cultural, and socioeconomic profile that influence migraine burden and management. Comprehensive multicenter data on patient characteristics, treatment access, and complementary and alternative medicine (CAM) use in this region are limited. The aim of this work was to compare sociodemographic and clinical characteristics of migraine patients in low-/lower-middle-income countries (LICs/LMICs) versus high-/upper-middle-income countries (HICs/UMICs) in the MENA region, and to explore disparities in medication access, treatment adherence, patient satisfaction, and CAM use.</p><p><strong>Methods: </strong>This cross-sectional multicenter study included 676 adult migraine patients across 12 MENA countries. Data were collected via structured interviews and medical record verification, covering sociodemographic, lifestyle, clinical, and treatment-related variables, as well as knowledge, attitudes, and experiences with CAM.</p><p><strong>Results: </strong>Patients from LICs/LMICs had significantly longer delays from headache onset to diagnosis compared with those from HICs/UMICs [6 (3-9) vs. 1 (0-3) years; effect size = 1.344, 95% CI: 1.175-1.511, P-value < 0.001]. Chronic migraine was significantly more prevalent in LICs/LMICs (44.3% vs. 20.8%; OR = 0.331, 95% CI: 0.236-0.463, P-value < 0.001), as was medication-overuse headache (38.5% vs. 15.0%; OR = 0.282, 95% CI: 0.195-0.406, P-value < 0.001). Access to medications was more restricted in LICs/LMICs, with 79.4% relying on out-of-pocket payments versus 42.1% in HICs/UMICs (OR = 0.210, 95% CI: 0.138-0.319, P-value < 0.001). Medication adherence was lower in LICs/LMICs (52.0% vs. 78.9%; OR = 3.458, 95% CI: 2.471-4.838, P-value < 0.001). Patient dissatisfaction with healthcare services was markedly higher in LICs/LMICs (35.5% vs. 7.9%, P-value < 0.001). Patients in LICs/LMICs reported greater reliance on traditional healers, religious leaders, and CAM modalities such as cupping, herbal remedies, and spiritual healing.</p><p><strong>Conclusion: </strong>This study highlights substantial disparities in migraine diagnosis and management between patients from LICs/LMICs and HICs/UMICs across the MENA region. Financial constraints and cultural influences may shape treatment adherence and CAM use in LICs/LMICs.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148382097","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":"Cerebrovascular reactivity in migraine: a breath-hold BOLD fMRI study.","authors":"Adam S Sprouse Blum, Richard Watts, Scott G Hipko, Jay V Gonyea, Anna E Senft-Miller, Olivia K Nop, Julie A Dumas, Robert E Shapiro, Benjamin Littenberg, Bruno P Soares, Lauren A DaSilva, James B Allison, Josh E Furlonge, Jiming Zhang","doi":"10.1186/s10194-026-02432-w","DOIUrl":"10.1186/s10194-026-02432-w","url":null,"abstract":"<p><strong>Background and objectives: </strong>Prior studies assessing cerebrovascular reactivity (CVR) in participants with migraine primarily utilized Doppler ultrasonography and focused on large vascular territories due to limitations of available technology. Newer functional MRI techniques detect alterations in CVR at much higher spatial resolution and, when coupled with an anatomical scan, allow correlation with specific brain regions. The goal of this study was to measure and compare CVR in participants with migraine during (ictal) versus between (interictal) spontaneous attacks using functional magnetic resonance imaging.</p><p><strong>Methods: </strong>This is an observational cohort study in which CVR was measured using breath-hold BOLD functional MRI during spontaneous migraine attacks involving lateralized headache. All participants returned for a repeat scan when free of all migraine symptoms. CVR was assessed by comparing BOLD activity during the ictal versus interictal scans in the entire group as well as by headache laterality.</p><p><strong>Results: </strong>Eighteen participants completed the study [77.8% female; mean (SD) age 38.4 (13.6) years]. Comparing the ictal to the interictal scan in the full cohort, no voxel clusters met significance criteria. When stratified by headache laterality, two significant clusters were identified (one decreased/one increased CVR) in 6 participants with right-sided headache. The cluster demonstrating decreased CVR was in the left planum temporale/left Heschl's gyrus. The cluster demonstrating increased CVR was in the right crus I of the cerebellum. No clusters met significance criteria in 12 participants with left-sided headache.</p><p><strong>Conclusion: </strong>Cerebrovascular reactivity was not observed to differ significantly during the ictal compared to the interictal state in the full cohort but did differ in the subgroup of participants with right-sided headache.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"27 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13330095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148382183","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":"Prelimbic cortex layer 5 GABAergic neurons mediate chronic pain and memory impairment by regulating excitatory/inhibitory imbalance.","authors":"Xiaoling Wang, Zhongyuan Lu, Tian Mao, Yitian Yang, Ruilou Zhu, Weiwei Li, Shuang Zeng, Yangyang Wang, Luyao Zhang, Yaowei Xu, Wei Zhang, Longjun Wu, Ji Hu, Mingyang Sun, Jiaqiang Zhang","doi":"10.1186/s10194-026-02439-3","DOIUrl":"10.1186/s10194-026-02439-3","url":null,"abstract":"<p><strong>Background: </strong>Chronic pain can cause both hyperalgesia and cognitive impairment symptoms and involves long-term alterations in the neural circuits, leading to abnormal cortical activity. GABAergic signaling are particularly emerging as relevant components of pain processing within the prefrontal cortex. The mechanism through which cortical circuits change and cause chronic pain and memory impairment remains unclear to date.</p><p><strong>Methods: </strong>We modeled chronic neuropathic pain in mice using chronic constrictive injury (CCI), an open field test, a Y maze spontaneous alternation experiment, a novel object recognition test and barnes maze were used to assess neurobehavioral changes in the mice. Whole-cell patch-clamp technique was used to assess the intrinsic activity of neurons, and fiber photometry recording was used to measure the calcium activity of GABAergic neurons. In vivo multi-channel technique was employed to assess alterations in cortical excitability. Western blot and immunofluorescence were used to measure the expression of activating transcription factor 4 (ATF4) and Neuronal excitability.</p><p><strong>Results: </strong>In this study, persistent elevation of GABAergic neuronal activity in prelimbic cortex layer 5 (PrL-L5) was demonstrated to regulate the chronic pain and memory impairment. This elevated GABAergic neuronal activity affects the excitatory/inhibitory (E/I) imbalance by influencing the excitability of pyramidal neurons. The inhibition of PrL-L5 GABAergic neuronal activity reversed the hypersensitivity and memory deficits. In contrast, the optogenetic activation of PrL-L5 GABAergic neurons induced hypersensitivity and memory impairment in naive mice. Furthermore, ATF4 regulates hyperpathia and memory impairment through impact GABAergic neuronal activity.</p><p><strong>Conclusion: </strong>We revealed a cortical GABAergic neural microcircuit that involved chronic pain and memory impairment through modulating E/I imbalance by influencing the excitability of pyramidal neurons. These findings provide novel insights for targeted interventions in patients with comorbid chronic pain and memory impairment.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13584424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148338870","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":"CXCL10 knockdown attenuates vestibular migraine in rats by inhibiting PI3K-mediated neuroinflammation and central sensitization.","authors":"Mao-Mei Song, Gianluca Coppola, Ying-Jie Gao, Shi-Na Song, Chang-Xin Li, Sui-Yi Xu","doi":"10.1186/s10194-026-02437-5","DOIUrl":"10.1186/s10194-026-02437-5","url":null,"abstract":"<p><strong>Background: </strong>Vestibular migraine (VM) is characterized by recurrent episodes of headache and vertigo, and its pathogenesis is closely associated with neuroinflammation and central sensitization. C-X-C motif chemokine ligand 10 (CXCL10) plays a critical role in neuroinflammation and pain modulation; however, its specific involvement in VM remains unclear.</p><p><strong>Methods: </strong>A rat model of VM was established by repeated intraperitoneal nitroglycerin injections combined with intratympanic kainic acid administration. To investigate the role of CXCL10, adeno-associated virus encoding CXCL10-targeted shRNA (CXCL10-shRNA-AAV) was delivered intracerebroventricularly prior to model induction. A rescue experiment was further performed using the PI3K agonist 740 Y-P to reactivate PI3K/AKT signaling. Mechanical pain thresholds (hind paw and periorbital), head scratching and grooming behavior, and vestibular function scores were assessed. Expression levels of CXCL10, CXCR3, PI3K/AKT pathway components, inflammatory cytokines (pro-IL-1β, IL-6, TNF-α), and central sensitization markers (CGRP, c-fos) in the trigeminal nucleus caudalis (TNC) and vestibular nuclei (VN) were examined by Western blot, qPCR, and immunofluorescence.</p><p><strong>Results: </strong>VM rats exhibited hyperalgesia, vestibular dysfunction, and upregulated CXCL10 expression in both TNC and VN. Intracerebroventricular delivery of CXCL10-shRNA-AAV effectively knocked down CXCL10 expression and significantly ameliorated pain hypersensitivity and vestibular deficits. Mechanistically, CXCL10 knockdown suppressed PI3K/AKT pathway activation, reduced pro-inflammatory cytokine production (pro-IL-1β, IL-6, TNF-α), and downregulated the central sensitization markers CGRP and c-fos in both TNC and VN. Notably, reactivation of the PI3K/AKT pathway by 740 Y-P partially reversed these effects.</p><p><strong>Conclusions: </strong>CXCL10 contributes to VM pathophysiology by activating PI3K/AKT-mediated neuroinflammation and promoting central sensitization. Targeted knockdown of CXCL10 attenuates both pain and vestibular symptoms in a rat VM model, highlighting CXCL10 as a potential novel therapeutic target for VM.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148338828","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":"Is migraine a spectrum disorder? Questioning the concept of \"episodic\" and \"chronic\" migraine using population-based data from 10,226 adults with migraine from 14 countries.","authors":"Andreas Kattem Husøy, Timothy J Steiner","doi":"10.1186/s10194-026-02440-w","DOIUrl":"10.1186/s10194-026-02440-w","url":null,"abstract":"<p><strong>Background: </strong>The first edition of the International Classification of Headache Disorders (ICHD-I) did not recognize chronic migraine (CM). ICHD-II introduced CM as a complication of migraine, with criteria that were widely criticized and later revised to require ≥ 15 monthly headache days (MHDs) with ≥ 8 monthly migraine days (MMDs). ICHD-3 reclassified CM as a type distinct from episodic migraine, retaining these frequency thresholds but without empirical justification. We investigated whether population-based evidence on headache characteristics and burden supported distinction between episodic and chronic migraine types, or indicated that migraine was better conceptualized as a single disorder expressed along a frequency spectrum.</p><p><strong>Methods: </strong>We performed a meta-analysis of individual participant data from 15 cross-sectional population-based surveys from the Global Campaign against Headache, all randomly selecting adults (18-65 years) and using the HARDSHIP questionnaire for data collection. Diagnoses made algorithmically observed the hierarchical order of ICHD. We identified four migraine groups: (1) migraine (definite+probable) including, and (2) migraine (definite+probable) excluding those with concomitant probable medication-overuse headache (pMOH); (3) migraine (definite only) including, and (4) migraine (definite only) excluding those with concomitant pMOH. MMDs and MHDs were regressed against headache characteristics, quality of life (QoL) and impaired participation.</p><p><strong>Results: </strong>Among 36,407 participants (mean age 37.5 years; 53.4% females), 10,266 (28.2%) met criteria for migraine (14.6% definite; 13.6% probable), including 896 (2.5%) with concomitant pMOH. Distributions of MMDs and MHDs were heavily right-skewed, peaking at 3 days/month, but showed no inflections at the thresholds for CM. Age was positively associated with headache frequency, while most headache characteristics varied minimally across frequencies. QoL declined slightly but linearly with increasing frequency, whereas lost workdays, household days and social days increased more-or-less linearly (albeit that household days plateaued after 15 days/3 months). Regressions were strikingly similar across genders and the four migraine groups.</p><p><strong>Conclusion: </strong>Population-based evidence indicates that migraine, considered in relation to headache frequency, characteristics and attributed burden, is better understood as a spectrum disorder rather than as two (or more) entities distinguished categorically by frequency. The current thresholds for CM do not align with detectable step-increments in headache characteristics or burden. These findings fill a major knowledge gap, usefully informing the development of ICHD-4.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"27 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13309956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148338853","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 among children and adolescents in Zambia: revised prevalence estimates, and estimates of attributed burden, from a national schools-based study.","authors":"Nfwama Kawatu, Somwe Wa Somwe, Ornella Ciccone, Derya Uluduz, Tayyar Şaşmaz, Bengü Nehir Buğdaycı Yalçın, Christian Wöber, Andreas Kattem Husøy, Timothy J Steiner","doi":"10.1186/s10194-026-02438-4","DOIUrl":"10.1186/s10194-026-02438-4","url":null,"abstract":"<p><strong>Background: </strong>In our earlier report of headache prevalence among children (6-11 years) and adolescents (12-17) in Zambia, we defined undifferentiated headache (UdH) conventionally as mild headache lasting < 1 h. However, we recognised diagnostic uncertainties, which also occurred in our similar studies elsewhere in sub-Saharan Africa (Ethiopia and Benin). Here we use a modified definition of UdH, making new estimates of prevalence accordingly, and estimates based on these of headache-attributed burden. The study was part of the global schools-based programme conducted by the Global Campaign against Headache.</p><p><strong>Methods: </strong>In a cross-sectional survey using the standardised protocol of the global programme, the child and adolescent versions of the HARDSHIP questionnaire, translated into the local languages, were completed by pupils in mediated sessions within their classes in nine schools representative of Zambia's urban/rural divide. Headache diagnostic questions were based on ICHD-3 except for UdH, which we redefined as mild or moderate headache lasting < 1 h. Enquiry included multiple aspects of attributed burden.</p><p><strong>Results: </strong>Of 2,759 potential participants, 2,089 (615 children [29.4%], 1,474 adolescents [70.6%]) completed questionnaires (participating proportion 75.7%). The unfeasibly high observed prevalence of migraine reported earlier (51.6%, including probable migraine) was reduced by redefining UdH to 42.9%, still highly questionable. Nonetheless, burden measures clearly distinguished migraine from tension-type headache (TTH) and UdH. Migraine headache was the most intense, most frequent and longest lasting, but proportion of time in ictal state (pTIS) was only 1.3%. However, pTIS was much greater among those with probable medication-overuse headache (7.9%) or other headache on ≥ 15 days/month (9.0%). Headache accounted for an estimated loss of 3.5% of school time in those affected, migraine having twice the impact of TTH or UdH, while H15 + accounted for > 15% of lost school time. Almost one in six parents (15.9%) lost time from their own work. Migraine had greater impact than TTH and UdH on both emotional impact and quality-of-life scores.</p><p><strong>Conclusions: </strong>Headache, prevalent among children and adolescents in Zambia, is associated with burdens that include lost school time, with, potentially, lifelong negative impact. These findings are of importance to national educational and health policies. Our modified definition of UdH was a step towards diagnostic veracity, but did not resolve the diagnostic difficulties among young people. Future studies might consider further modifications, but full review of the ICHD criteria for migraine in these age groups is needed.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13330355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148330471","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 the shared genetic architecture between migraine subtypes and cardiovascular diseases: a multi-layered genomic analysis.","authors":"Yiming Liu, You Ma, Yiwei Liu","doi":"10.1186/s10194-026-02433-9","DOIUrl":"10.1186/s10194-026-02433-9","url":null,"abstract":"<p><strong>Background: </strong>Epidemiological studies have linked migraine to an increased risk of cardiovascular disease (CVD); however, the shared genetic basis and putative causal relationships between migraine subtypes and cardiovascular traits remain poorly understood.</p><p><strong>Methods: </strong>Leveraging large-scale GWAS summary statistics for migraine phenotypes (overall migraine, migraine with aura [MA], and migraine without aura [MO]) from FinnGen R12, along with seven cardiovascular diseases from publicly available consortia, we conducted a multi-layered genetic analysis. This integrative framework encompassed genetic correlation [linkage disequilibrium score regression (LDSC) and high-definition likelihood (HDL)], cross-trait meta-analysis (CPASSOC and PLACO), Bayesian colocalization, summary-data-based Mendelian randomization (SMR) using GTEx v8 eQTL data, and bidirectional two-sample Mendelian randomization (MR).</p><p><strong>Results: </strong>Significant genetic correlations were identified between migraine and multiple cardiovascular traits, with hypertension and coronary artery disease (CAD) showing the most robust associations. MA exhibited broader genetic overlap with cardiovascular diseases than MO, including a notably stronger correlation with ischemic stroke, whereas MO demonstrated a stronger correlation with hypertension. Cross-trait meta-analysis identified 160 pleiotropic loci across 17 of 21 trait pairs. Colocalization analysis confirmed 32 loci harboring shared causal variants, mapped to 13 candidate genes, of which 7 (PHACTR1, LRP1, SOX7, ABO, FHOD3, MEI1, XKR6) were further validated by SMR as exhibiting tissue-specific regulatory effects. Among these, PHACTR1 displayed the broadest pleiotropic profile across migraine phenotypes and vascular diseases. After MR-PRESSO outlier removal, bidirectional MR identified 10 MR-supported associations, two of which (genetic liability to hypertension on overall migraine, and CAD on MA) survived Bonferroni correction, all free of detectable horizontal pleiotropy. Genetic liability to hypertension was associated with increased migraine risk (OR = 1.90, 95% CI 1.25-2.90, P = 2.64 × 10⁻³), atherosclerotic diseases showed subtype-specific effects (inverse for MO, positive for MA), and, in the reverse direction, migraine was associated with increased ischemic stroke risk.</p><p><strong>Conclusions: </strong>This study provides a comprehensive and systematic characterization of the shared genetic architecture between migraine subtypes and cardiovascular diseases. By identifying pleiotropic genes and bidirectional putative causal relationships with subtype-specific patterns, our findings carry implications for the development of targeted therapeutics and subtype-specific cardiovascular risk stratification.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13560339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148330505","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}