Journal of Headache and Pain最新文献

{"title":"Gnao1 acts as a gatekeeper to alleviate neuropathic pain by silencing pro-nociceptive signaling cascades.","authors":"Jieyi Cai, Hui Li, Lü Chen, Ling Luo, Xin Wu, Min Yuan, Maolin Han, Shirong Wen, Changlai Zhu, Yun Gu","doi":"10.1186/s10194-026-02436-6","DOIUrl":"10.1186/s10194-026-02436-6","url":null,"abstract":"<p><strong>Background: </strong>Neuropathic pain is a debilitating condition with limited effective treatments, highlighting an urgent need for non-opioid analgesic targets. Gαo, encoded by the Gnao1 gene, is an abundant G protein in the nervous system and couples to multiple inhibitory GPCRs, but its role in chronic pain remains poorly understood.</p><p><strong>Methods: </strong>Spatial transcriptomics and bulk RNA-sequencing were performed on the spinal cord and dorsal root ganglia (DRG) of mice following spared nerve injury (SNI). Adeno-associated virus (AAV)-mediated Gnao1 overexpression or knockdown was performed in the spinal cord or DRG, followed by pain behavioral testing using von Frey filaments, acetone evaporation test, and mechanical conflict avoidance (MCA) assay. Microglial activation, neuronal injury, and signaling pathways were examined by immunohistochemistry (IHC), Western blotting (WB), and calcium imaging. In vitro studies used BV2 microglia and primary DRG neurons with lentiviral Gnao1 overexpression and LPS or db-cAMP stimulation.</p><p><strong>Results: </strong>Spatial transcriptomics revealed that Gnao1 is enriched in the spinal dorsal horn (SDH) and significantly downregulated after SNI. Bulk RNA-seq confirmed Gnao1 downregulation in pain-processing regions (DRG and SDH). IHC showed that its cellular localization shifted from neurons to glial cells. Overexpression of Gnao1 in the spinal cord or DRG markedly alleviated SNI-induced mechanical allodynia, cold hypersensitivity, and pain-related avoidance behaviors. Mechanistically, transcriptomic profiling revealed that Gnao1 overexpression broadly suppressed pro-inflammatory and pro-nociceptive pathways. Experimental validation confirmed that Gnao1 overexpression reduced p38, ERK, and NF-κB phosphorylation, and decreased microglial activation. In primary DRG neurons, Gnao1 overexpression also lowered cAMP levels and suppressed db-cAMP-evoked Ca²⁺ influx.</p><p><strong>Conclusion: </strong>Gnao1 acts as a gatekeeper negative regulator of neuropathic pain by silencing distinct pro-nociceptive signaling cascades, and highlights its potential as a non-opioid analgesic target.</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":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13551804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308258","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":"Vestibular cortex-related effective connectivity signatures: characterization and differentiation of vestibular migraine patients via magnetic resonance imaging and machine learning.","authors":"Lingling Dai, Guangzheng Li, Yixiang Lin, Chao Zheng, Wen Chen, Qifang Feng, Xing Xiong, Yang Yu, Hongru Zhao, Jun Ke","doi":"10.1186/s10194-026-02430-y","DOIUrl":"10.1186/s10194-026-02430-y","url":null,"abstract":"<p><strong>Background: </strong>Neuroimaging studies of vestibular migraine (VM) have revealed abnormal functional connectivity in the central vestibular system. However, it remains to be determined whether effective connectivity (EC) of the vestibular cortex is specifically disrupted in VM and whether this brain measure can aid in the differential diagnosis of VM patients.</p><p><strong>Methods: </strong>In 56 VM patients, 58 episodic migraine (EM) patients, and 63 healthy controls (HCs), the directional influences between the vestibular cortex and the whole brain were examined via resting-state functional magnetic resonance imaging and Granger causality analysis, with bilateral parietal operculum cortex 2 (OP2) as the seed regions. Statistical analyses were performed to investigate the group differences and the associations of directional influences with clinical variables. Classification models based on linear support vector machine (SVM) analysis were established to assess the performance of effective connectivity in discriminating VM patients from HCs and EM patients.</p><p><strong>Results: </strong>Relative to the EM group and HC group, the VM group presented elevated positive influence from the left OP2 to the right middle frontal gyrus (MFG), as well as increased negative influence from the right MFG and inferior parietal lobule (IPL) to the left OP2. Furthermore, the EM group exhibited increased positive influence from the bilateral medial superior frontal gyrus (SFGmed) to the left OP2 compared with the VM group and HC group. The EC-derived SVM models showed favorable and moderate performance for distinguishing VM patients from EM patients (area under the curve = 0.8264, p < 0.001) and HCs (area under the curve = 0.7764, p < 0.001).</p><p><strong>Conclusions: </strong>The causal flow from and to the left OP2 was altered in the prefrontal and inferior parietal lobes, regions closely implicated in cognitive control and multisensory integration. Abnormal EC associated with the right MFG and IPL appears to be specific to VM, whereas altered EC linked to SFGmed suggests a resilience trait in EM. The EC of the OP2 may serve as a neuroimaging biomarker for VM identification.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13551776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308238","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":"Long-term headache following cerebral venous thrombosis: a systematic review.","authors":"Diana Doukhi, Jerome Mawet, Caroline Roos, Mikael Mazighi, Isabelle Crassard","doi":"10.1186/s10194-026-02429-5","DOIUrl":"10.1186/s10194-026-02429-5","url":null,"abstract":"<p><strong>Background: </strong>Cerebral venous thrombosis (CVT) predominantly affects young adults and frequently presents with headache. Although functional outcomes are generally favorable, many patients report persistent or recurrent headache long after the acute event. This systematic review aimed to assess the prevalence, clinical characteristics, associated factors, and management of long-term headache following CVT.</p><p><strong>Main body: </strong>A systematic search of PubMed and Embase (2000-2025) identified studies reporting original data on long-term headache after CVT in adult populations. Case series including fewer than 30 patients were excluded. Given substantial heterogeneity in study design, definitions, and outcome measures, a qualitative synthesis was performed. Fifteen studies including 2,136 patients were analyzed. The reported prevalence of post-CVT headache ranged from 14% to 59%. Headache most often resembled primary headache disorders, particularly tension-type and migraine-like phenotypes. Available data suggest that de novo headache may represent the most frequent presentation, although modification of pre-existing headache disorders also occurs. Pre-existing headache and depression were associated with post-CVT headache, whereas intracerebral hemorrhage was not. Associations with venous recanalization, thrombosis location, and anticoagulation delay were inconsistent. Secondary mechanisms, including intracranial hypertension, dural arteriovenous fistula, CVT recurrence, and medication-overuse headache, were identified in some patients. Data on management strategies were limited.</p><p><strong>Conclusion: </strong>Long-term headache is a frequent but under-recognized complication of CVT that may significantly impact quality of life. The absence of a standardized definition contributes to heterogeneity across studies. After exclusion of secondary causes, post-CVT headache encompasses both de novo and modified primary headache phenotypes. A consensus term such as \"new or modified recurrent headache attributed to past CVT\" may help describe this spectrum and improve clinical characterization and future research.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13543559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148301984","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":"Atogepant reduces triptan use: a pharmacoeconomic analysis in migraine prevention.","authors":"Simona Guerzoni, Lanfranco Pellesi, Lisa Giannessi, Flavia Lo Castro, Maria Chiara Olivieri, Luca Degli Esposti, Francesca Gandolfi","doi":"10.1186/s10194-026-02434-8","DOIUrl":"10.1186/s10194-026-02434-8","url":null,"abstract":"<p><strong>Background: </strong>Migraine is a leading cause of disability worldwide, impairing quality of life and productivity. Preventive therapies aim to reduce attack frequency, severity and the need for acute medications. Oral atogepant (60 mg), a calcitonin gene-related peptide (CGRP) receptor antagonist, has recently expanded migraine prevention options. This study evaluated changes in triptan use after atogepant initiation using real-world data.</p><p><strong>Methods: </strong>This retrospective observational study used administrative healthcare databases from the Local Health Unit of Modena (Italy). Adults with chronic or high-frequency episodic migraine initiating atogepant between November 2023 and December 2024 were identified. Triptan use and related costs were assessed in the 6 months before and after treatment initiation (index date), measured as dispensed dosage units.</p><p><strong>Results: </strong>Among 95 patients (86% female; mean age 53.5 years), 55 triptan users were included in the analysis. Triptan use decreased in 45 patients (82%), with ≥ 60% reduction in 27 (49%) and complete discontinuation in 10. Median consumption decreased from 76 to 24 dosage units, and mean consumption from 88.1 to 45.2. This reduction was statistically significant (Wilcoxon signed-rank test, p < 0.001). This reduction corresponded to a decrease of €2,591 in triptan-related pharmaceutical expenditure within the study cohort.</p><p><strong>Conclusion: </strong>Atogepant preventive treatment may substantially reduce acute migraine medication use in real-world practice, with potential clinical and economic benefits.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13292513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148295352","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":"Periventricular diffusivity at the ventricular-parenchymal interface across healthy controls, episodic migraine, and chronic migraine: a cross-sectional multimodal MRI study.","authors":"Fangwang Fu, Chenyu Dai, Chenyu Lin, Xiaoqing Liu, Zi Tao, Xiaojie Zhang, Xinhao Li, Mengqian Ye, Tong Xu, Yixuan Hu, Kun Liu, Yungang Cao, Keyang Chen, Beilei Hu, Xiaozheng Liu, Jing Sun, Yan Li","doi":"10.1186/s10194-026-02427-7","DOIUrl":"10.1186/s10194-026-02427-7","url":null,"abstract":"<p><strong>Background: </strong>Chronic migraine (CM) carries high disability, yet interictal MRI phenotypes that distinguish CM from episodic migraine (EM), particularly in medication-overuse headache (MOH)-inclusive cohorts, remain incompletely characterized. We tested whether periventricular diffusivity (PVeD), an indirect MRI marker of tissue-water properties at the ventricular-parenchymal interface, is associated with CM and headache burden.</p><p><strong>Methods: </strong>In this cross-sectional 3.0-T multimodal MRI study, 289 adults with complete structural MRI, diffusion MRI, and resting-state fMRI were analyzed: 67 healthy controls, 162 EM, and 60 CM. MOH was diagnosed and retained in the CM group. MRI was acquired during verified interictal evening sessions; participants with headache within 24 hours before or after MRI were excluded. The primary contrast was age- and sex-adjusted CM versus EM for PVeD. Secondary analyses examined MOH strata, headache-frequency strata, partial Spearman correlations, Firth logistic regression for CM status, and HIT-6 models.</p><p><strong>Results: </strong>Age- and sex-adjusted PVeD was lower in CM than EM (adjusted difference, -0.011; 95% CI, -0.017 to -0.006; standardized difference, -0.71; p < 0.001) and healthy controls (-0.014; 95% CI, -0.021 to -0.007; standardized difference, -0.88; p < 0.001), with no EM-control difference. Both CM participants with and without MOH had lower PVeD than EM. In migraine participants, lower PVeD correlated with higher headache frequency, HIT-6, and MIDAS and with larger choroid plexus volume and smaller thalamic, nucleus accumbens, and putaminal volumes. In the expanded clinical-plus-MRI Firth model, each 1-SD higher PVeD was associated with lower CM odds (OR, 0.59; 95% CI, 0.38 to 0.89; p = 0.011). Higher PVeD was associated with lower HIT-6 after adjustment for headache frequency or MOH.</p><p><strong>Conclusions: </strong>CM was associated with lower PVeD at the ventricular-parenchymal interface, and lower PVeD was linked to patient-centered burden in this MOH-inclusive cohort. PVeD is not yet a diagnostic or treatment-selection biomarker, but may help define an MRI phenotype for future chronification-risk and treatment-response studies after longitudinal and external validation.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13540849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148283899","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":"Sleep quality and chronotype in primary headache disorders: a nationwide population-based study of 5,311 Polish adults.","authors":"Karol Marschollek, Helena Martynowicz, Sławomir Budrewicz, Marcin Straburzyński, Marta Waliszewska-Prosół","doi":"10.1186/s10194-026-02425-9","DOIUrl":"10.1186/s10194-026-02425-9","url":null,"abstract":"<p><strong>Background: </strong>Primary headache disorders, particularly migraine, are closely linked to sleep disturbances. However, the relationship between headache phenotypes, sleep quality, and chronotype in large populations remains to be fully elucidated. This study aimed to investigate sleep quality and chronotype across different primary headache types compared to headache-free individuals.</p><p><strong>Methods: </strong>This nationwide, cross-sectional study included 5,311 Polish adults recruited via an online research panel. Headaches were classified using the HARDSHIP questionnaire according to ICHD-3 criteria. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and chronotype using the Morningness-Eveningness Questionnaire (MEQ). Sleep-related variables were then compared between specific headache types and individuals without headache.</p><p><strong>Results: </strong>Participants with migraine (n = 1,523) reported the poorest sleep quality (median PSQI: 7 vs. 5 in controls) and the highest prevalence of poor sleep (64.1% vs. 38.7% in controls; p < 0.001). After adjustment, migraine (β = 2.09), unclassified headache (β = 1.57), and tension-type headache (TTH; β = 0.59) remained significantly associated with higher PSQI scores. Regarding chronotype, the migraine group showed a significant shift toward eveningness (adjusted β=-1.38; p < 0.001) and a lower representation of morning types (24.9% vs. 39.1% in controls). In the migraine subgroup, poorer sleep quality was moderately correlated with lower quality of life (r=-0.45) and higher perceived stress (r = 0.34), whereas MEQ scores showed only weak correlations with clinical outcomes.</p><p><strong>Conclusions: </strong>Poor sleep quality and an evening chronotype are prominent features of primary headache disorders, especially migraine. Future prospective studies are needed to determine the causality of these associations. Meanwhile, sleep quality assessment and interventions aiming to improve sleep patterns should be considered in migraine patients.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13285201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148283921","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":"The emerging role of the meningeal lymphatic and glymphatic systems in migraine pathophysiology: a systematic review.","authors":"Kimia Bagheri, Hadi Sahrai, Negin Safari Dehnavi, Niloofar Taheri, Ali Norouzi, Mahnaz Talebi, Reza Mosaddeghi-Heris, Amirreza Naseri","doi":"10.1186/s10194-026-02431-x","DOIUrl":"10.1186/s10194-026-02431-x","url":null,"abstract":"<p><strong>Background/objective: </strong>Migraine is a common, debilitating neurological disorder of unclear pathophysiology. Recent evidence has implicated impaired meningeal lymphatic function and its interaction with the glymphatic system in the development of neuroinflammation and pain sensitization. This systematic review aimed to summarize existing evidence on the role of the meningeal lymphatic and glymphatic systems in migraine pathophysiology.</p><p><strong>Methods: </strong>Following the PRISMA 2020 recommendations, we searched PubMed, Web of Science, and Scopus from inception to December 15, 2025. Inclusion criteria comprised human or animal studies examining meningeal lymphatic or glymphatic function in migraine or validated migraine animal models. SYRCLE's risk of bias tool for animal studies and the Joanna Briggs Institute (JBI) critical appraisal tools were used for quality assessment.</p><p><strong>Results: </strong>The search yielded a total number of 457 records, out of which 10 articles fulfilled the eligibility criteria. These comprised six imaging studies conducted on human populations and four preclinical studies performed on animal models. Studies using dynamic contrast-enhanced (DCE)-MRI have shown changes in lymphatic enhancement characteristics in both episodic and chronic migraines. Diffusion tensor imaging along perivascular spaces (DTI-ALPS) yielded heterogeneous findings, with abnormalities more consistently observed in chronic and high-frequency migraine. Preclinical models demonstrated that cortical spreading depression, nitroglycerin exposure, and familial hemiplegic migraine mutations impaired glymphatic influx and reduced cerebrospinal fluid efflux through meningeal lymphatic vessels.</p><p><strong>Discussion: </strong>Initial research has shown that altered lymphatic and glymphatic systems may be related to migraine. Nonetheless, there is no existing literature on whether these conditions can be considered causative agents for migraines. There is a need for longitudinal imaging studies in a larger population.</p><p><strong>Registration: </strong>PROSPERO ID: CRD420251266296.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"27 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13281639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148277551","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":"Long-term safety and continued clinical benefit of erenumab 70 mg in Asian patients with chronic migraine: an open-label extension of the phase 3 DRAGON study.","authors":"Shengyuan Yu, Byung-Kun Kim, Hebo Wang, Jiying Zhou, Partha Banerjee, Jeremie Lincy, Evgeniya Reshetnyak, Zheng Li, Denise Leclair, Shuu-Jiun Wang","doi":"10.1186/s10194-026-02406-y","DOIUrl":"10.1186/s10194-026-02406-y","url":null,"abstract":"<p><strong>Background: </strong>Erenumab is a fully human monoclonal antibody targeting the calcitonin gene-related peptide receptor. Several double-blind studies have demonstrated the clinical benefits of erenumab in migraine prevention. However, long-term studies on safety and effectiveness of erenumab are lacking in Asian population.</p><p><strong>Objectives: </strong>To evaluate the long-term safety and continued clinical benefit of erenumab 70 mg in adult patients with chronic migraine (CM) in China and other Asian countries.</p><p><strong>Methods: </strong>This was an open-label extension of the Phase 3 DRAGON study. Upon completion of the 12-week, double-blind treatment phase (DBTP) of the DRAGON study, randomized patients who met the inclusion criteria and provided consent transitioned into an open-label treatment phase (OLTP) lasting until erenumab approval in the patient's country. During OLTP, patients received once-monthly subcutaneous injection of erenumab 70 mg, irrespective of their initial treatment allocation in DBTP. Safety was assessed by collecting all adverse events (AEs) and serious AEs (SAEs) including their severity and relationship to study treatment. Effectiveness outcomes included clinical global impression (CGI) [severity (CGI-S), improvement (CGI-I), and efficacy index (CGI-E)].</p><p><strong>Results: </strong>Of the 557 randomized patients (DBTP), 456 from 50 centers participated and 226 (49.6%) completed OLTP. The median duration of exposure to erenumab was 79.9 weeks (interquartile range: 39.9-130.5). Overall, 328 (71.9%) patients reported at least one AE during OLTP. AEs suspected to be related to treatment were reported in 69 (15.1%) patients, with constipation (34 [7.5%]) being the most frequent treatment-related AE. There were 13 (2.9%) patients who discontinued the study drug due to AEs. Breast cancer was reported as an AE leading to discontinuation in 2 (0.4%) patients (not treatment related). SAEs were reported in 45 (9.9%) patients during OLTP, of which only 3 (0.7%) were treatment-related (all resolved). Continued clinical benefit with erenumab 70 mg as assessed by CGI E/I/S scores were observed for participating patients during OLTP.</p><p><strong>Conclusion: </strong>Erenumab 70 mg showed a consistent and well-tolerated safety profile observed over a longer treatment duration along with sustained clinical benefit. No new safety signals were observed versus DBTP and prior global phase 3 studies.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov ID (DRAGON) NCT03867201 (registration date 2019-03-07).</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13508234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148271511","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":"Clinical characteristics of perimenopausal migraine and its correlation to hormonal levels.","authors":"Lobna Talaat El-Ghoneimy, Nervana M Elfayoumy, Hanan Helmy, Menatallah Mohamed Saleh Elaguizy, Anter Mothenna Abdullah Nasser, Hend Abdelghany","doi":"10.1186/s10194-026-02418-8","DOIUrl":"10.1186/s10194-026-02418-8","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Studies about perimenopausal migraine are limited. In this study, we aimed to explore the characteristics of perimenopausal migraine and to compare perimenopausal women with and without migraine in terms of the levels of Estradiol and Follicle-Stimulating Hormone (FSH). We also aimed to correlate migraine severity scores with Estradiol and FSH levels.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A case-control study of 66 subjects divided as Group 1 (n = 22): migraine onset during perimenopause, Group 2 (n = 22) migraine onset before perimenopause, and Group 3 (n = 22) age-matched healthy controls. Perimenopausal women with any type of migraine (age 40-55 years) were eligible. We excluded secondary and other primary headaches, hormonal therapy and chronic illness. Subjects underwent a detailed history taking of headache and vasomotor symptoms, MIDAS and VAS scores. Measurement of Estradiol (E2) and FSH levels was done for all participants. Comparisons were done between group 1 and group 2 by migraine characteristics, vasomotor symptoms and Estradiol and FSH levels. Group 3 (control) was compared with both migraine groups 1 and 2 by vasomotor symptoms and Estradiol and FSH levels. Statistical analysis was performed by using SPSS 27th edition Statistical tests used include mean, median, count, Mann-Whitney U, Kruskal-Wallis test, Chi-squared test and the Spearman correlation test (The suitable test was chosen based on the type of variables and data, and the number of comparison groups).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Migraine with onset during perimenopause was characterized by throbbing pain, alternating laterality, orbito-fronto-temporal site, moderate to severe intensity, high frequency, with associated phonophobia and photophobia, while autonomic symptoms were rare. There was analgesic overuse and an unsatisfactory response. Group 2 significantly had more postdrome symptoms, less analgesic response and more menstrually-triggered migraine than Group 1 (P &lt; 0.05). Both perimenopausal migraine groups (Group 1 and 2) had significantly more perimenopausal symptoms, including fatigue, sleep disturbance, mood symptoms and anxiety (P &lt; 0.05) compared to the control (Group 3). Hot flashes, night sweating and vaginal dryness were more common in migraineurs without statistical significance. Migraineurs had significantly lower Estradiol levels and a higher proportion of subjects with Estradiol &lt; 50 pg./ml than controls (P &lt; 0.05). There was a significant negative correlation between Estradiol and scores, including MIDAS (Rho=-0.406, P = 0.007) and VAS (Rho= -0.331, P = 0.030). No difference in the FSH levels among the Groups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Perimenopause is associated with high-frequency, moderate to severe migraine headache. Lower Estradiol levels were correlated with high migraine severity scores (VAS and MIDAS). The frequency of perimenopausal symptoms is higher, whereas the Estradiol level is lower in migrainous ","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"27 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13274107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148264865","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":"CGRP-provoked headache is associated with a neuroimmune signature in idiopathic intracranial hypertension.","authors":"Andreas Yiangou, Thien Phu Do, Olivia Grech, Caroline W Mugo, Chloe N Thomas, Jessie Gew, Maria G Lange, Megan Gee, Susan P Mollan, Lisa J Hill, Samuel J E Lucas, Messoud Ashina, Alexandra J Sinclair","doi":"10.1186/s10194-026-02385-0","DOIUrl":"10.1186/s10194-026-02385-0","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic intracranial hypertension (IIH) is characterised by raised intracranial pressure and disabling headaches, yet its underlying mechanisms remain poorly defined. Calcitonin gene-related peptide (CGRP) is a key neuropeptide implicated in migraine and headache attributed to IIH. CGRP-driven neuroinflammation is implicated in migraine generation but whether CGRP-provoked headache in IIH is accompanied by dynamic neuroimmune activation during the ictal phase remains unknown. We aimed to characterise cytokine alterations during experimentally-induced IIH headache attacks provoked by CGRP.</p><p><strong>Methods: </strong>In a randomised, double-blind, placebo-controlled, two-way crossover study (IIH Provoke: ISRCTN13251508), 16 women with IIH underwent two inpatient visits receiving intravenous CGRP (1.5 µg/min for 20 min) or placebo (isotonic saline). Blood samples were collected at baseline and either at peak headache or at the end of the visit, if no headache occurred. Plasma cytokines were measured using the Olink^® Target 48 Cytokine Panel. CGRP induced a typical IIH headache attack within the sampling period in 7/16 participants.</p><p><strong>Results: </strong>Compared with baseline, eight cytokines were significantly elevated during CGRP-provoked headache attacks: C-C motif chemokine 4 (CCL4), CCL8, interleukin-6 (IL-6), IL-17C, IL-27, oncostatin M (OSM), hepatocyte growth factor (HGF), and transforming growth factor-α (TGF-α) (P < 0.05). These changes were not observed after placebo or in participants who received CGRP without developing headache.</p><p><strong>Conclusions: </strong>CGRP-provoked IIH headache attacks were associated with elevations in pro-nociceptive mediators (IL-6, CCL4, OSM) and immune-related cytokines (IL-17C, IL-27, HGF, TGF-α). These findings suggest that CGRP-provoked headache in IIH is associated with changes in circulating cytokines consistent with a neuroimmune response during the ictal phase. Larger cohorts are required to validate these observations and explore neuroinflammation as a therapeutic target in IIH headache.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13285290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148251737","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}