Journal of Headache and Pain最新文献

{"title":"Association between headaches and lifestyle factors and physical and mental symptoms among 63,071 workers at a Japanese information technology company.","authors":"Masako Yokoyama, Hisaka Igarashi, Hirohisa Kato, Tetsuji Yokoyama, Hiroshi Ebihara, Yasuhiro Azuma, Fumihiko Sakai, Hitoshi Miyake, Satoko Nagumo","doi":"10.1186/s10194-025-02065-5","DOIUrl":"10.1186/s10194-025-02065-5","url":null,"abstract":"<p><strong>Background: </strong>Headaches are common and can significantly affect working conditions. To reduce their occurrence at work, identifying factors associated with headaches is important. We aimed to investigate the association between headaches and lifestyle factors, as well as physical and mental symptoms, among workers at the Fujitsu Group, a Japanese information technology company, to identify factors contributing to workplace headaches.</p><p><strong>Methods: </strong>The results of a 2022 Stress Check Survey questionnaire (mandated by Japanese occupational law requirements) were evaluated concerning 63,071 Fujitsu Group workers (men, n = 50,360; [mean age ± standard deviation, 45.6 ± 10.7 years]; women, n = 12,711 [41.8 ± 11.5 years]).</p><p><strong>Results: </strong>The headache rates according to frequency category (seldom, sometimes, often, and almost always) were as follows: men, 48.8%, 34.2%, 13.9%, and 3.1%, respectively, and women, 33.6%, 39.9%, 21.0%, and 5.5%, respectively. Multiple logistic regression analysis of lifestyle factors showed that the odds ratio (OR [95% confidence interval]) for headache (sometimes, often, or almost always) was highest in the presence of \"high stress levels\" (men, 7.13 [6.57-7.73]; women, 8.79 [7.07-10.94]). Other lifestyle factors included \"seldom exercising\" (men, 1.47 [1.36-1.60]; women, 1.55 [1.27-1.89]) and \"weekday sitting time > 12 h\" (men, 1.35 [1.27-1.43]; women, 1.61 [1.40-1.84]). The population attributable fraction for \"exercise habits,\" \"high stress levels,\" and \"sitting time\" in men was 26.1%, 8.4%, and 5.2%, respectively, and 30.5%, 5.4%, and 4.9%, in women, respectively. Further analysis regarding physical and mental symptoms showed that the ORs for headache increased with the presence of \"stiff shoulders\" (men, 3.65 [3.37-3.96]; women, 5.08 [4.26-6.05]), \"insomnia\" (men, 2.71 [2.41-3.05]; women, 2.61 [2.00-3.41]), \"eye strain\" (men, 2.62 [2.40-2.86]; women, 2.31 [1.93-2.76]), \"depression\" (men, 2.35 [2.06-2.69]; women, 2.35 [1.76-3.14]), \"back pain\" (men, 1.66 [1.53-1.80]; women, 2.08 [1.75-2.40]), and \"anxiety\" (men, 1.32 [1.18-1.48]; women, 1.55 [1.20-2.00]).</p><p><strong>Conclusions: </strong>This large-scale survey among Japanese workers revealed the strength of the association between headaches and various lifestyle factors, and physical and mental symptoms. These findings could guide workplace interventions to decrease headaches among workers.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"129"},"PeriodicalIF":7.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142695","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":"Ergotamine enhances circadian amplitude and diurnally mitigates nitroglycerin-induced mechanical hypersensitivity.","authors":"Chorong Han, Hwayoung Baek, Ji Ye Lim, Eunju Kim, Celia K Tran, Emma Freeman, Zheng Chen, Seung-Hee Yoo, Mark J Burish","doi":"10.1186/s10194-025-02008-0","DOIUrl":"10.1186/s10194-025-02008-0","url":null,"abstract":"<p><strong>Background: </strong>Cluster headache and migraine have a circadian timing of attacks and are linked to the trigeminovascular system. Recently the trigeminal ganglion was found to have a strong circadian rhythm, with the serotonin 2A receptor identified as a clock-controlled gene. Ergotamine is an acute treatment for cluster headache and migraine, acts on the trigeminal ganglion, and is a serotonin 2A receptor agonist. The circadian properties of ergotamine are unknown.</p><p><strong>Methods: </strong>We performed real-time bioluminescence monitoring and qPCR of Per2::LucSV reporter mouse fibroblast cultures after treatment with ergotamine. We examined receptor effects by treating Per2::LucSV fibroblast cultures with ergotamine and one of several serotoninergic, adrenergic, and/or dopaminergic receptor antagonists. Next, we treated Per2::LucSV reporter mouse trigeminal ganglion explants with ergotamine and monitored circadian reporter rhythms; finally we measured hindpaw sensitivity in a nitroglycerin chronic headache mouse model and administered ergotamine at two different times to examine a chronotherapeutic effect on pain behavior.</p><p><strong>Results: </strong>Ergotamine caused a more than two-fold increase in the amplitude of Per2::LucSV fibroblasts without a change in period length; amplitude enhancement was also seen for expression of Clock, Bmal1, Period3, Cryptochrome2, Rev-erbα, and Rev-erbβ. Ergotamine's effect on circadian amplitude was dampened by the serotonin-1B/1D receptor antagonist GR127935, the serotonin-1D receptor antagonist BRL1557, the serotonin-1A/1B/2A/2B/2C, alpha1A-adrenergic, and dopamine D1-4 receptor antagonist asenapine, and the serotonin-2C receptor antagonist SB242084. In contrast to serotonin receptor antagonists, ergotamine's effects on clock amplitude were unchanged by other serotonin antagonists or by selective adrenergic or dopaminergic receptor antagonists, suggesting that ergotamine's amplitude effect is mediated by serotonin receptor activation. Furthermore, trigeminal ganglion explant cultures treated with ergotamine showed a significant increase in amplitude without a change in period. Finally, in the nitroglycerin chronic headache mouse model, ergotamine significantly raised hindpaw thresholds when administered during the daytime (ZT4) but not at night (ZT16).</p><p><strong>Conclusions: </strong>Ergotamine has substantial circadian rhythm modification effects in both cellular and animal models. Ergotamine's circadian effects appear to be mediated through serotonin 1D and 2C receptors, providing a rationale for why sub-psychedelic doses of psilocybin (which induces psychedelic responses through the serotonin 2A receptor) might be effective. Ergotamine's peak effect on hindpaw thresholds at ZT4 suggests that ergotamine may be more effective at certain times of day.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"127"},"PeriodicalIF":7.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12100948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132422","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":"Nuclear paraspeckle assembly transcript 1 promotes photophobia behavior in mice via miR-196a-5p/Trpm3 coupling.","authors":"Zhuoan Huang, Xingshen Li, Xiaolin Wang, Jiaqi Wu, Ziyang Gong, Sulev Kõks, Minyan Wang","doi":"10.1186/s10194-025-02057-5","DOIUrl":"10.1186/s10194-025-02057-5","url":null,"abstract":"<p><strong>Background: </strong>The long noncoding RNA, NEAT1, is recognized as a key regulator of proinflammatory gene expression; Yet, its functional role in migraine remains unexplored, despite the central role of neuroinflammatory mechanisms in migraine pathophysiology. This study examines the implication of NEAT1 in the trigeminal ganglion activation, which underlies photophobia associated with migraine.</p><p><strong>Methods: </strong>Light aversion behavior was induced by intranasal injection of the TRPA1 activator, umbellulone. Male mouse behavior was assessed by the total time the mouse stays in the light between the dark and light compartments. To gain insight to the NEAT1-mediated photophobia mechanism, gene expression of candidate genes and non-coding RNAs interactions were assessed using RNA-sequencing, qPCR analysis, histology and dual-luciferase reporter gene assay.</p><p><strong>Results: </strong>NEAT1 was upregulated in the trigeminal ganglion of male photophobia mice; Downregulation of NEAT1 by intravenous injection of shNEAT1 adeno-associated virus vectors attenuated NEAT1 expression and alleviated photophobia-like behavior in mice. The elevated NEAT1 expression in the trigeminal ganglion of photophobia mice corresponds to the downregulation of miR-196a-5p and upregulation Trpm3 RNA level. Predicted analysis suggested NEAT1/miR-196a-5p ceRNA network exists in photophobia mice. Indeed, knocking down NEAT1 upregulated miR-196a-5p, whilst downregulated Trpm3 gene expression level, in the trigeminal ganglion of photophobia mice. Further investigation using dual-luciferase reporter gene assay identified NEAT1 interacting with miR-196a-5p, whilst miR-196a-5p interacting with Trpm3. Similar to knocking down NEAT1, TRPM3 inhibition reduced photophobia-like behavior.</p><p><strong>Conclusion: </strong>We conclude that NEAT1 is critical for promoting photophobia behavior via miR-196a-5p/Trpm3 coupling.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"118"},"PeriodicalIF":7.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119873","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":"Unravelling the gut-brain connection: a systematic review of migraine and the gut microbiome.","authors":"Caroline W Mugo, Ella Church, Richard D Horniblow, Susan P Mollan, Hannah Botfield, Lisa J Hill, Alexandra J Sinclair, Olivia Grech","doi":"10.1186/s10194-025-02039-7","DOIUrl":"10.1186/s10194-025-02039-7","url":null,"abstract":"<p><strong>Background: </strong>There is substantial evidence linking migraines to gastrointestinal (GI) issues. Conditions such as irritable bowel syndrome and colitis often co-occur with migraines and GI symptoms are common among migraine patients. However, the evidence supporting the efficacy of gut microbiome-targeted therapies for managing migraines is limited. This systematic review aimed to describe the existing evidence of the gut microbiome in patients with migraine compared to healthy individuals. Additionally, it sought to examine how therapies targeting the gut microbiome including prebiotics, probiotics and synbiotics, might influence clinical outcomes.</p><p><strong>Methods: </strong>We performed searches on Embase, PubMed, and the Cochrane Library to identify studies in migraines and the gut microbiome, focusing on those which investigated the gut microbiome composition and gut microbiome-targeted therapies. Key data was extracted and analysed including study details, patient demographics, migraine type, comorbidities, and clinical outcomes. For gut microbiome composition studies, bacterial diversity and abundance was noted. For gut microbiome-targeted therapies studies, treatment types, dosages, and patient outcomes was recorded.</p><p><strong>Results: </strong>A significant difference between various genera of microbes was reported between migraine patients and controls in several studies. Bacteroidetes (also named Bacteroidota), proteobacteria, and firmicutes (also named Bacillota) phyla groups were found significantly abundant in migraine, while studies were conflicted in the abundance of Actinobacteria and Clostridia with regards to increased migraine risk in migraine patients. Patients with migraine had a gut microbiome with reduced species number and relative abundance, as well as a distinct bacterial composition compared to controls. Synbiotic and synbiotic/probiotic combination treatments have been shown in five randomised controlled trials and one open label pilot study to significantly decrease migraine severity, frequency, duration and painkiller consumption.</p><p><strong>Conclusions: </strong>The significant alterations in microbial phyla observed in migraine patients suggest a potential microbial signature that may be associated with migraine risk or chronic progression. However, the mechanistic underpinnings of these associations remain unclear. This systemic review found that probiotic and synbiotic/probiotic combination therapies may be promising interventions for migraine management, offering significant reductions in migraine frequency and painkiller use. Future randomised controlled studies are needed to evaluate the optimal length of treatment and impact on patient related quality of life.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"125"},"PeriodicalIF":7.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119839","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":"Reliability and validity of the Arabic version of cluster headache impact questionnaire in both active episodic and chronic cluster headache.","authors":"Mona Hussein, Mona Af Nada, Amr Hassan, Mohamed Abdelghaffar, Mona Ali, Alaa Elmazny, Rehab Magdy","doi":"10.1186/s10194-025-01991-8","DOIUrl":"10.1186/s10194-025-01991-8","url":null,"abstract":"<p><strong>Background: </strong>Clinical evaluation of cluster headache (CH) impact on patients' quality of life is crucial in research and clinical practice. To our knowledge, none of the measures that evaluated CH-related disability were validated in Arabic. This study aimed to evaluate the reliability and validity of the Arabic version of Cluster Headache Impact Questionnaire (CHIQ) in both active episodic CH (eCH) and chronic CH (cCH).</p><p><strong>Methods: </strong>Patients with active eCH or cCH were requested to answer the Arabic version of CHIQ, Depression, anxiety and stress scale- 12 (DASS-12), and Short form-12 health survey (SF-12). Cronbach's α and intraclass correlation coefficient (ICC) were used to assess the test reliability. Convergent validity and Explanatory factor analysis of CHIQ items were also assessed.</p><p><strong>Results: </strong>Seventy-two patients with active eCH and another 16 with cCH were evaluated. Patients with cCH had a significantly higher median value of CHIQ total score in comparison to those with eCH (P-value < 0.001). No ceiling or floor effects were detected in CHIQ total score. The Arabic version of CHIQ showed excellent reliability (Cronbach's α = 0.901). The intraclass correlation coefficient of CHIQ total score was 0.983 indicating excellent test re-test reliability. The CHIQ scores were significantly correlated with scores of DASS-12 (r = 0.477) and SF-12 (r=-0.691), supporting the convergent validity of the scale. Exploratory factor analysis revealed two factors labelled as \"physical and cognitive impact\" and \"psychological impact\" factors.</p><p><strong>Conclusion: </strong>Arabic version CHIQ is a reliable and valid tool for measuring CH-related disability and quality of life in patients with eCH and cCH.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"126"},"PeriodicalIF":7.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119838","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":"Induction of more severe central sensitization in a medication overuse headache model mice through active ingestion of rizatriptan.","authors":"Zhenjie Ma, Chenhao Li, Wenhao Bai, Wei Xie, Mingjie Zhang, Han Xiao, Cancan Chen, Yang Li, Wenwen Zhang, Deqi Zhai, Yingyuan Liu, Dengfa Zhao, Wenjing Tang, Zhao Dong, Ruozhuo Liu, Shengyuan Yu","doi":"10.1186/s10194-025-02066-4","DOIUrl":"10.1186/s10194-025-02066-4","url":null,"abstract":"<p><strong>Background: </strong>Medication overuse headache (MOH) is a secondary headache disorder arising from excessive use of acute analgesics in patients with primary headache. Current animal models that predominantly employ passive drug administration fail to recapitulate the hallmark feature of voluntary medication-seeking behaviour observed clinically. Therefore, we established a novel MOH mouse model with the active ingestion of rizatriptan (RIZ) to better simulate the clinical characteristics of MOH and explore changes in brain activation patterns.</p><p><strong>Methods: </strong>C57BL/6 J mice received intraperitoneal injections of nitroglycerin (NTG, 10 mg/kg) every other day. During the feeding period, they were provided with two bottles-one containing an RIZ solution (0.02 mg/kg) and the other containing deuterium depleted water (DDW)-allowing for voluntary intake. The bottle containing the RIZ solution was marked with a fixed colour indicator at the nozzle. Behavioural assessments included mechanical allodynia (von Frey filaments), anxiety-like behaviours (elevated plus maze, EPM and open field test, OFT), and drug-seeking quantification. Quantitative data from c-Fos immunostaining across 25 specific brain regions were subjected to Z score normalization, followed by three-tiered computational analyses: 1) hierarchical clustering (complete linkage) to characterize activation patterns, 2) Pearson correlation analysis for functional connectivity mapping, and 3) graph-theoretical network analysis (Cytoscape 3.2.1) to identify hub regions and their topological relationships. The small molecule calcitonin gene-related peptide (CGRP) receptor antagonist, rimegepant (100 mg/kg, i.p., 7 injections) was administered during the modelling period, and withdrawal of RIZ and NTG was applied after modelling to observe behavioural and histological changes.</p><p><strong>Results: </strong>Chronic RIZ consumption exacerbated NTG-induced cutaneous allodynia, prolonged central sensitization, and increased anxiety-like behaviour. Rimegepant attenuated allodynia progression, whereas withdrawal of RIZ and NTG normalized pain thresholds. Network analysis identified the prelimbic cortex (PrL) and spinal trigeminal nucleus caudalis (SPVC) as hub nodes. The PrL exhibited extensive functional connectivity with addiction-related regions (the insular cortex, IC and nucleus accumbens), whereas the SPVC showed predominant connections with pain-processing areas.</p><p><strong>Conclusion: </strong>This study pioneers an ethologically valid MOH model that reflects more severe central sensitization and recapitulates active medication-seeking behaviour. PrL-mediated addiction-like-behaviour pathways and SPVC-centred nociceptive processing may play roles in the development of MOH. These findings provide novel neuromodulation targets (PrL, IC, SPVC) for refractory MOH management.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"123"},"PeriodicalIF":7.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109888","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":"Genetic influence of the brain imaging phenotypes, brain and cerebrospinal fluid metabolites and brain genes on migraine subtypes: a Mendelian randomization and multi-omics study.","authors":"Ping-An Zhang, Jie-Lin Wang, Mei-Hua Dong, Xiang-Chun Huang, Nai-Jian Li, Run-Dong Qin, Jing Li","doi":"10.1186/s10194-025-02063-7","DOIUrl":"10.1186/s10194-025-02063-7","url":null,"abstract":"<p><strong>Background: </strong>Migraine is a complex neurological disorder with high prevalence but unclear pathogenesis. Numerous studies have suggested that migraine is associated with alterations in brain imaging phenotypes (BIPs) and dysregulation of cerebrospinal fluid (CSF) and brain metabolism; however, causal evidence remains limited. Mendelian randomization (MR) offers a powerful approach for inferring causality using genetic instruments.</p><p><strong>Methods: </strong>Firstly, we conducted linkage disequilibrium score regression (LDSC) to evaluate genetic correlations between migraine, including the migraine with aura (MA) and migraine without aura (MO) subtypes, and BIPs, CSF, and brain metabolites. Traits that showed genetic correlations with migraine, MA, or MO were retained for subsequent MR analysis with the corresponding migraine phenotype. Traits showing significant correlations were analyzed using bidirectional two-sample MR (TSMR), followed by two-step TSMR to identify cross-omics mediation effects. Additionally, We also applied summary-data-based MR (SMR) to detect brain-region-specific genes with potential causal effects. Enrichment analyses (KEGG, GO, PPI, transcription factor, and miRNA networks) were conducted to further explore underlying mechanisms.</p><p><strong>Results: </strong>LDSC identified significant genetic correlations with 73 BIPs and 40 metabolites for overall migraine, 71 BIPs and 37 metabolites for MA, and 49 BIPs and 62 metabolites for MO. Enrichment analysis revealed that genetically associated metabolites were predominantly involved in amino acid metabolic pathways. TSMR identified 6 BIPs and 2 metabolites causally linked to overall migraine, 3 BIPs and 3 metabolites to MA, and 2 BIPs and 5 metabolites to MO. Most migraine-related BIPs mapped to the parietal lobe. Reverse MR analysis showed that overall migraine causally influenced 4 BIPs and 3 metabolites, while MA and MO affected 1 BIP and 1 metabolite, and 3 BIPs and 1 metabolite, respectively. Mediation analysis revealed five significant mediation pathways were identified. SMR analysis identified FAM83B and CIB2 consistently showing inhibitory effects across most regions. Enrichment analysis showed that these genes were predominantly involved in immune activation and cell adhesion.</p><p><strong>Conclusions: </strong>Our study integrates cross-omics analyses to investigate the causal links between brain structure, metabolic alterations, gene expression, and migraine including its MA and MO subtypes. These findings provide novel insights into the pathophysiological mechanisms and potential targets for intervention across migraine subtypes.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"124"},"PeriodicalIF":7.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110925","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":"Dysfunctional mesocorticolimbic circuitry in cluster headache.","authors":"Stefania Ferraro, Greta Demichelis, Jean Paul Medina Carrion, Dan Liu, Benjamin Becker, Michael Maes, Davide Fedeli, Giuseppe Ciullo, Susanna Usai, Marina Grisoli, Luisa Chiapparini, Alberto Cecchini Proietti, Luca Giani, Anna Nigri, Massimo Leone","doi":"10.1186/s10194-025-02017-z","DOIUrl":"10.1186/s10194-025-02017-z","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to identify mesocorticolimbic functional abnormalities in cluster headache (CH) patients, disentangling the roles of chronification and affective symptoms.</p><p><strong>Methods: </strong>Using the monetary incentive delay fMRI task to directly engage these pathways, we investigated functional alterations in key regions of this network in chronic (n = 23) and episodic CH patients (n = 49) compared to a control group (n = 32). After processing the fMRI data, we extracted beta values from selected regions and for contrasts of interest and entered them into logistic regression models adjusted for potential confounders (such as depressive and anxiety symptoms and smoking habit) to test their association with the diagnoses (chronic CH and control subjects, episodic CH and control subjects).</p><p><strong>Results: </strong>Results showed that chronic CH patients exhibited reduced ventral tegmental area (VTA) activity and a tendency towards significance (p = 0.056) for an increased medial prefrontal cortex (mPFC) responsiveness during reward anticipation, alongside a significant decrease in mPFC activity during reward outcomes. Episodic patients displayed abnormal mPFC activity across both reward phases, but coupled with intact VTA responses. Importantly, these functional abnormalities were not correlated to depressive and anxiety symptoms and smoking habits.</p><p><strong>Conclusions: </strong>These findings suggest that chronic CH patients experience an imbalance in the VTA-mPFC pathway, while episodic patients may show early signs of this emerging dysfunction. Moreover, the observed reward processing alterations seem distinct from those associated with affective disorders, possibly highlighting unique mechanisms underlying the pathophysiology of CH.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"121"},"PeriodicalIF":7.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110922","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 impact of CSF venous fistula embolization on patient's quality of life, a longitudinal clinical-radiological exploration.","authors":"Malo Goapper, Liesjet E H van Dokkum, Vincent Costalat, Gaetano Risi, Lucas Corti, Olivia Portalier, Nicolas Lonjon, Emmanuelle Le Bars, Anne Ducros, Federico Cagnazzo","doi":"10.1186/s10194-025-02056-6","DOIUrl":"10.1186/s10194-025-02056-6","url":null,"abstract":"<p><strong>Background: </strong>Transvenous Onyx embolization of cerebrospinal fluid-venous fistulas (CSFVF) is an emerging and effective treatment for symptomatic spontaneous intracranial hypotension (SIH). This condition significantly impacts patients' quality of life (QoL) through a variety of debilitating symptoms.</p><p><strong>Methods: </strong>Patients were selected from a prospective database of individuals with CSFVF who underwent transvenous Onyx embolization. All participants were asked to complete 13 questionnaires assessing their QoL, before and three months after treatment. Clinical and radiological data were retrospectively collected from the database, and the impact of embolization was evaluated across multiple variables. Correlations and stepwise regression analyses were used to explore relationships between QoL and specific domains including headache, audio-vestibular and psychological symptoms, and spiritual well-being.</p><p><strong>Results: </strong>The study included 30 patients (mean age: 60.4 ± 14.1; female-to-male ratio: 2:1) diagnosed with SIH and CSFVF, that were treated successfully with Onyx embolization. There was no treatment-related morbidity. All 28 patients with headache reported symptom improvement, with 64% achieving complete resolution. The response rate was 100% for VAS-QoL, HIT-6, MIDAS grade, VAS-HI, and monthly headache days; lower rates were observed for SF-36 (56.6%), MSQ (96.7%), DHI and THI (90%), and psychological questionnaires (80-90%). Global QoL scores (VAS-QoL: p < 0.001, SF-36: p < 0.05) and QoL scores related to headache significantly improved post-treatment (HIT-6: p = 0.0119; MSQ: p = 0.0004; MIDAS: p = 0.0236). Psychological symptoms like depression and anxiety significantly decreased, while suicidal ideation resolved when present. Significant audio-vestibular QoL improvements were noted for dizziness (p = 0.002) and hearing disturbances (p = 0.021), but not for tinnitus (p = 0.101). MRI findings showed a significant reduction in SIH-related brain abnormalities (mean Bern-score: 6.3 ± 1.9 to 1.7 ± 1.5 post-treatment). However, changes in overall Bern-scores did not correlate with clinical variables, although brain sagging showed a trend toward correlation with headache intensity reduction (r = 0.37, p = 0.06).</p><p><strong>Conclusion: </strong>CSFVF embolization is associated with significant radiological and clinical improvements, leading to enhanced global quality of life for patients with SIH.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"120"},"PeriodicalIF":7.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101814","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":"GIANT: a prospective, multicenter, real-world study on the effectiveness, safety, and tolerability of atogepant in migraine patients with multiple therapeutic failures.","authors":"Piero Barbanti, Gabriella Egeo, Francesca Pistoia, Cinzia Aurilia, Paola Scatena, Steno Rinalduzzi, Silvia Strumia, Antonio Salerno, Fabio Frediani, Andrea Galli, Massimo Autunno, Laura Di Clemente, Maurizio Zucco, Maria Albanese, Francesco Bono, Pietrantonio Bruno, Laura Borrello, Stefano Messina, Alberto Doretti, Angelo Ranieri, Cecilia Camarda, Rosario Vecchio, Valeria Drago, Giulia Fiorentini, Carlo Tomino, Stefano Bonassi, Paola Torelli, Alice Mannocci","doi":"10.1186/s10194-025-02068-2","DOIUrl":"10.1186/s10194-025-02068-2","url":null,"abstract":"<p><strong>Background: </strong>Atogepant, the first oral CGRP receptor antagonist approved for migraine prevention, has demonstrated efficacy and safety in randomized clinical trials (RCT). However, prospective real-world data are lacking.</p><p><strong>Objective: </strong>To explore the effectiveness, safety, and tolerability of atogepant 60 mg at week 12 in patients with high-frequency episodic (HFEM: 8-14 days/month) or chronic migraine (CM) with multiple therapeutic failures.</p><p><strong>Methods: </strong>This ongoing, multicenter (n = 16), prospective real-world study included consecutive adults with HFEM or CM who had failed ≥3 prior preventive treatments, according to AIFA criteria. Participants received atogepant 60 mg daily, with treatment planned for up to 12 months.</p><p><strong>Primary endpoint: </strong>change from baseline to week 12 in monthly migraine days (MMD) for HFEM and monthly headache days (MHD) for CM. Secondary endpoints: changes in monthly analgesic intake (MAI), pain intensity (NRS), disability (HIT-6, MIDAS), interictal burden (MIBS-4), treatment satisfaction (PGIC), responder rates (≥ 50%, ≥ 75%, 100%), and changes in migraine frequency during the first treatment week compared to the last pre-treatment week. Adverse events were monitored throughout.</p><p><strong>Results: </strong>A total of 183 patients were enrolled and 82 completed ≥ 12 weeks of follow-up. Of these, 41.5% had previously failed anti-CGRP mAbs. At week 12, significant reductions (p < 0.001) were observed in MMD (-6.0) and MHD (-11.2). Secondary outcomes also improved significantly (p < 0.001): MAI (-10.9), NRS (-2.7), HIT-6 (-13.2), MIDAS (-61.1), and MIBS-4 (-5.4). Responder rates were 65.9% (≥ 50%), 36.6% (≥ 75%), and 6.1% (100%). PGIC documented high satisfaction (much/very much improved: 70.7%). A significant decrease (p < 0.001) in migraine frequency was already evident by week 1 (overall: - 2.5 days, HFEM: - 1.5, CM: - 3.1). In the mAb-failure subgroup, ≥ 50% and ≥ 75% response rates were 52.9% and 23.5%, with significant improvements in all primary and secondary endpoints (p < 0.001). Adverse events occurred in 5.5% of patients, and 1.6% discontinued treatment.</p><p><strong>Conclusion: </strong>The GIANT study provides real-world evidence of atogepant's effectiveness, safety, and tolerability in patients with HFEM and CM with multiple therapeutic failures and comorbidities. It extends RCT data by showing rapid onset of action, meaningful reductions in pain intensity and interictal disability, high patient satisfaction, and effectiveness even in patients with anti-CGRP mAb failures.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"122"},"PeriodicalIF":7.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208712","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}