Journal of Headache and Pain最新文献

{"title":"Substance P release from rat dura mater is inversely correlated with CGRP release- experiments using glycerol trinitrate and anti-CGRP antibodies.","authors":"Mária Dux, Karl Messlinger","doi":"10.1186/s10194-025-02050-y","DOIUrl":"10.1186/s10194-025-02050-y","url":null,"abstract":"<p><strong>Background: </strong>The neuropeptides calcitonin gene-related peptide (CGRP) and substance P are important mediators of neurogenic inflammation when they are released from activated primary nociceptive afferents. It is long evident that neuropeptides play an important role in migraine pathophysiology, but the significance of neurogenic inflammation is still debated.</p><p><strong>Methods: </strong>In an approved hemisected rodent head preparation, we measured CGRP release from the cranial dura mater in parallel with substance P release using animals pre-treated with anti-CGRP antibodies or control solutions.</p><p><strong>Results: </strong>Apart from the known decrease in CGRP release following antibody treatment, we found a significant inverse correlation of basal and stimulated CGRP versus substance P release across all experiments. The results are discussed in connection with our previously published data.</p><p><strong>Conclusions: </strong>An increase in CGRP release seems to inhibit substance P release in meningeal structures possibly decreasing substance P-dependent plasma extravasation, which argues against a significant role of neurogenic inflammation in migraine.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"119"},"PeriodicalIF":7.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086358","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":"Prevalence, disability, and economic impact of migraine in Spain: a nationwide population-based study.","authors":"Margarita Sanchez-Del-Rio, David García-Azorín, Carmen Peral, Beatriz Armada, Pablo Irimia-Sieira, Jesus Porta-Etessam","doi":"10.1186/s10194-025-02069-1","DOIUrl":"10.1186/s10194-025-02069-1","url":null,"abstract":"<p><strong>Background: </strong>This study updates data on migraine prevalence in Spain, examining regional variations, healthcare resource utilization (HCRU), and patient-reported outcomes (PROs).</p><p><strong>Methods: </strong>Cross sectional study using data from the 2022 National Health and Wellness Survey, an online survey of Spanish residents aged 18 or older. Respondents diagnosed with migraine by a physician and who reported at least one migraine in the past year were considered active migraine cases.</p><p><strong>Results: </strong>The study included 7,002 respondents, 930 of whom had physician-diagnosed active migraine. The estimated one-year prevalence of migraine in Spain was 13.1% (95% confidence interval [CI] 12.8-13.4%), with higher rates in females (17.7%, 95% CI 17.2-18.3%) than in males (8.2%, 95% CI 7.8-8.6%). Migraine prevalence varied across Spain's regions, ranging from 8.1% (95% CI 5.2-11.0%) in Navarre to 19.1% in Cantabria (95% CI 15.6-22.6%). Prevalence was the highest among individuals earning below the median income (14.7%, 95% CI 14.1-15.4%). In the preceding month, 75.3% of patients experienced < 4 migraine days, 15.3% 4-9 migraine days, 4.1% 10-14 migraine days, and 5.3% ≥15 migraine days. Severe disability from migraine was reported by 20.4% of respondents. One in ten people reported using a preventive treatment for migraine. The mean SF-12 scores for mental and physical health were 37.8 and 42.1, respectively, both below the general population norm of 50. The mean EQ-5D summary score was 0.8, indicating reduced quality of life and the PHQ-9 detected severe depressive symptoms in 8.8% of individuals. Work productivity was affected by migraine, with a mean work productivity loss of 35.8%. HCRU in the preceding 6 months was high, with 68.4% having visited at least once a general practitioner, 14.2% a neurologist, 45.6% the emergency room, and 11.8% being hospitalized. The annual cost per person with migraine was estimated at €6,704, primarily driven by indirect costs related to productivity loss.</p><p><strong>Conclusions: </strong>Migraine prevalence remains high in Spain, causing a substantial burden and representing a major public health problem. Despite the availability of effective treatments, their usage is limited. Improving migraine management should be prioritized to enhance health outcomes and reduce societal burden.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"117"},"PeriodicalIF":7.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078546","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":"Astrocytic spermidine insufficiency contributes to enhanced pain sensitivity associated with ApoE4.","authors":"Kaiming Yu, Xiongyao Zhou, Baolong Li, Jialu Sun, Tuo Yang, Weizhen Li, Ningning Wang, Xiaosong Gu, Shusen Cui, Rangjuan Cao","doi":"10.1186/s10194-025-02054-8","DOIUrl":"10.1186/s10194-025-02054-8","url":null,"abstract":"<p><p>Neuropathic pain is a chronic condition with limited effective treatments, closely associated with astrocytes and their role in central sensitization. Apolipoprotein E (ApoE), predominantly expressed in astrocytes in central nervous system, exists in three ApoE isoforms (ApoE2, ApoE3, and ApoE4) in humans, with ApoE4 linked to increased susceptibility to neurological diseases. However, the relationship between ApoE4 and neuropathic pain, as well as underlying mechanisms, remains poorly understood. Here, we demonstrated that mice expressing human ApoE4 (ApoE4-TR) displayed increased pain sensitivity following spared nerve injury (SNI) compared to ApoE3-TR mice. This increased sensitivity was also observed in mice with astrocyte-specific expression of ApoE4, achieved through Cre-mediated recombination. Metabolomic profiling revealed reduced spermidine levels in the spinal dorsal horn of ApoE4-TR mice relative to ApoE3-TR mice. Daily gavage administration of spermidine alleviated mechanical pain to a comparable level in ApoE3-TR and ApoE4-TR mice, as assessed by von Frey test. However, lower dose of spermidine effectively alleviated neuropathic pain in ApoE3-TR mice but showed reduced efficacy in ApoE4-TR mice, likely due to limited spermidine retention in ApoE4 astrocytes, as demonstrated in vitro. Transcriptomic analysis identified Nos2 as a critical gene upregulated in ApoE4-TR mice. Mechanistically, spermidine suppressed Nos2 expression by inhibiting the NF-κB pathway in astrocytes, thereby alleviating neuropathic pain. These findings highlight an enhanced pain sensitivity associated with ApoE4 and suggest spermidine as a potential therapeutic strategy, emphasizing a tailored dosage approach for ApoE4 carriers.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"116"},"PeriodicalIF":7.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078545","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":"White matter and cortical gray matter microstructural alterations in migraine: a NODDI and DTI analysis.","authors":"Zhilei Li, Yanliang Mei, Lei Wang, Tianhua Fan, Cheng Peng, Kaibo Zhang, Shouyi Wu, Tong Chen, Zhenchang Zhang, Binbin Sui, Yonggang Wang, Xueying Yu","doi":"10.1186/s10194-025-02059-3","DOIUrl":"https://doi.org/10.1186/s10194-025-02059-3","url":null,"abstract":"<p><strong>Background: </strong>The pathophysiological mechanism of migraine remains elusive, thereby impeding the effective treatment of the disease. Current neuroimaging research focuses on changes in brain functional connectivity, functional networks, and macrostructural alterations, which reflect abnormal neuronal function during the disease process. The plasticity changes in neuronal structures and neurotransmitter system dysregulations potentially play a crucial role in migraine onset and chronicity of migraine. This study utilizes multimodal neuroimaging techniques to investigate the microstructural and neurotransmitter alterations in migraine and provides new insights into its pathological mechanisms and therapeutic method.</p><p><strong>Methods: </strong>Microstructural alterations in both white matter (WM) and cortical gray matter (GM) were evaluated among 40 chronic migraine (CM) patients, 35 episodic migraine (EM) patients, and 45 healthy controls (HCs) using Diffusion Tensor Imaging (DTI) and Neurite Orientation Dispersion and Density Imaging (NODDI) models. Tract-based spatial statistics (TBSS) and Surface-based analysis (SBA) were performed to compare groupwise differences in white and gray matter microstructure, respectively. Furthermore, the cross-modal toolbox JuSpace was used to analyze the correlation between cortical gray matter neurite alterations and neurotransmitter.</p><p><strong>Results: </strong>In the WM, compared to HC, a decrease in neurite density index (NDI) was identified in the migraine group, and both NDI and fractional anisotropy (FA) were decreased in the CM group. No significant alterations were observed in the EM group. An increase in radial diffusivity (RD) was found in the CM group compared to the EM group. In the cortical GM, compared to HC, the migraine group had fewer neurites in the right insula and temporal pole cortex, and the CM group showed a reduction in neurites in the right middle temporal and fusiform cortex. The cortical GM of neurite damage was negatively correlated with neurotransmitters in migraine and CM. There was no correlation between NODDI and DTI metrics of these brain regions and clinical data after the Bonferroni correction.</p><p><strong>Conclusion: </strong>Our findings indicated that neurite loss was detected in both WM and cortical GM of migraineurs. As the migraine progresses into chronicity, the axonal damage may become more pronounced. The neurite damage of cortical GM was negatively related to neurotransmitters.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"115"},"PeriodicalIF":7.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078547","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":"Burden of migraine among Egyptian people: prevalence and comorbidities.","authors":"Ahmed Amir Samir, Ahmed W Hageen, Ahmed Elgammal, Mostafa Meshref, Mennatullah A El-Refaay, Mohamed Medhat Taalap, Ali Elsaeed Nassef, Rawan Ali Bedewe, Ahmed Almeldein, Ibrahim Ali Kabbash","doi":"10.1186/s10194-025-02016-0","DOIUrl":"10.1186/s10194-025-02016-0","url":null,"abstract":"<p><strong>Introduction: </strong>Migraine is a prevalent debilitating neurological illness that stands among the top causes of disability and significantly impacts the quality of life. Migraine-related functional impairment involves physical, emotional, and economic consequences that frequently impact occupational, academic, social, and familial aspects of life. Depression, anxiety, and sleep disturbances are among the most common comorbid conditions associated with migraine.</p><p><strong>Objective: </strong>This study aimed to assess the prevalence of migraine among the Egyptian population and associated comorbidities.</p><p><strong>Methods: </strong>we conducted a cross-sectional study using a validated Arabic self-administered questionnaire distributed to the general population. The questionnaire was used to collect data on sociodemographic characteristics, migraine frequency, characteristic associated disability, insomnia, and psychological factors. Convenience snowball sampling method was utilized. Univariate and multivariate regression analyzes were applied.</p><p><strong>Results: </strong>A total of 2,533 participants were included in the final analysis from five Egyptian regions. Females represent 57%. More than one-half of participants (59.1%) aged 20-30 years. The prevalence of migraine was 20.9%. The most common triggers were sleep disorders (76.9%), followed by perceived noise (65%), and anxiety (59%). Among the participants diagnosed with migraine, 46.7% had a severe disability, 22% had clinical insomnia of moderate severity, 20.5% had severe depression, 29% had severe anxiety, and 20.6% had severe stress. Females, older age, and urban residents were the key predictors of migraine. Lifestyle factors including regular physical activity and good hydration were linked to reduced migraine risk. Comorbid conditions including insomnia, stress, and anxiety significantly impacted migraine severity.</p><p><strong>Conclusion: </strong>Our results showed a 20.9% prevalence of migraine, with nearly one-half of cases associated with severe disability, along with comorbidities like depression, anxiety, and insomnia. Female gender, older age, and urban residence are key predictors, while lifestyle factors such as physical exercise and good hydration reduce the risk of migraine.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"114"},"PeriodicalIF":7.3,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029330","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":"Unraveling the paradox: cardiovascular risk profiling in migraine- a correspondence.","authors":"Linda Al-Hassany, Ruben W A van Drie, Deirdre M Boucherie, Antoinette MaassenVanDenBrink","doi":"10.1186/s10194-025-02060-w","DOIUrl":"10.1186/s10194-025-02060-w","url":null,"abstract":"<p><p>We read with great interest the recent publication by Marston and colleagues in Nature Medicine, entitled \"Endothelial cell-related genetic variants identify LDL cholesterol-sensitive individuals who derive greater benefit from aggressive lipid lowering\" (issue 31, March 2025, pages 963-969). Among their compelling findings, the association between the endothelial cell-specific polygenic risk score (EC-PRS) - which consists of SNPs associated with coronary artery disease - and a reduced risk of migraine headaches stood out, although not being the study's primary aim. Migraine imposes a substantial individual and socioeconomic burden worldwide. Beyond its neurological manifestations as a primary headache disorder, migraine has increasingly been recognized as an independent and underappreciated cardiovascular risk factor, linked to major cardiovascular and cerebrovascular events. However, the biological underpinnings of this association remain poorly understood, particularly since they do not appear to be mediated through traditional or atherosclerotic pathways, and they are not associated with established cardiovascular risk factors. In this Correspondence, we build upon the findings of Marston et al. and contextualize them within the broader framework of migraine as a neurovascular disorder. Drawing from translational evidence, we propose a conceptual model that integrates findings regarding EC-PRS into the complex biological interplay linking migraine and cardiovascular disease, including coronary artery disease. In doing so, we aim to advance our understanding of migraine not only as a neurological disorder but as a marker of vascular vulnerability with implications for future research regarding personalized cardiovascular prevention, including statin therapy.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"113"},"PeriodicalIF":7.3,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144008374","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":"Differential inhibitory effects of endocannabinoids on neuronal firing of mouse meningeal afferents.","authors":"Georgii Krivoshein, Adriana Della Pietra, Juha Savinainen, Arn M J M van den Maagdenberg, Rashid Giniatullin","doi":"10.1186/s10194-025-02041-z","DOIUrl":"10.1186/s10194-025-02041-z","url":null,"abstract":"<p><strong>Background: </strong>Increasing endocannabinoids (endoCBs), anandamide (AEA) and 2-arachidonoylglycerol (2-AG), through inhibition of the degrading hydrolase enzymes, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively, has been proposed as approach to alleviate migraine pain. Notwithstanding, the impact of AEA and 2-AG on neuronal firing of meningeal afferents, which is relevant to the genesis of migraine pain, remains elusive.</p><p><strong>Methods: </strong>The impact of AEA and 2-AG on meningeal nerve afferent firing was examined through electrophysiological evaluation upon application of 50 mM KCl with or without DMSO, exogenous AEA (10 µM), or 2-AG (10 µM) to separate groups of C57BL/6J mouse hemiskull preparations. At the end of each experiment, capsaicin (1 µM), an agonist of TRPV1 channels, was tested, as a positive control of presumably nociceptive firing. Advanced clustering and spectral analysis on the electrophysiological data allowed differentiating spiking patterns with respect to their temporal and neurochemical profiles. Activity-based protein profiling and liquid chromatography with tandem mass spectrometry was used to assess endogenous FAAH and MAGL activity and determine endogenous levels of AEA and 2-AG in mouse meninges.</p><p><strong>Results: </strong>Local application of endoCBs decreased KCl-induced firing of meningeal nerve afferents, which was most profound for AEA. AEA first produced a short, mild activation in firing, which was followed by a long-lasting reduction. Instead, 2-AG directly led to a short-lasting reduction in firing. Cluster analysis revealed that the transient activation by AEA involved fibers with small-amplitude spikes fired at rates of 1-2 Hz, whereas the persistently suppressed fibers consisted of high-amplitude spikes fired at rates exceeding 10 Hz. Only AEA inhibited subsequent capsaicininduced firing in the afferents long after AEA application, suggesting a broader mode of action for AEA than 2-AG. The more profound inhibitory effects of AEA are consistent with the observed higher activity of FAAH over MAGL and lower level of endogenous AEA than 2-AG in mouse meninges.</p><p><strong>Conclusion: </strong>Our study revealed a stronger anti-nociceptive action of AEA than of 2-AG, as measured by meningeal afferent firing in mouse hemiskulls. This difference can be exploited for relieving migraine pain by primarily increasing the tone of AEA through inhibition of FAAH outside the central nervous system.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"112"},"PeriodicalIF":7.3,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995875","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 interictal transcriptomic map of migraine without aura.","authors":"Peter Petschner, Sahel Kumar, Duc A Nguyen, Dora Torok, Zsofia Gal, Daniel Baksa, Kinga Gecse, Gyongyi Kokonyei, Hiroshi Mamitsuka, Gabriella Juhasz","doi":"10.1186/s10194-025-02033-z","DOIUrl":"https://doi.org/10.1186/s10194-025-02033-z","url":null,"abstract":"<p><strong>Background: </strong>The present study aimed to deliver a replicable transcriptomic map of migraine without aura (MO) and its comprehensive, genome- and drug discovery focused analysis to identify hypotheses for future research- and clinical attempts.</p><p><strong>Methods: </strong>We recruited 30 controls and 22 MO patients without serious chronic comorbidities/regular medication intake. RNA-sequencing was conducted interictally at two different time points to identify replicable differential gene expression and enriched pathways. Subsequent refining and functional analyses were performed, including: 1) testing additional patient factors, 2) running genetic association analysis on migraine in the UK Biobank (UKB) and our cohort, and 3) predicting drug binding with AutoDock Vina and machine learning to proteins of transcriptomic changes.</p><p><strong>Results: </strong>Difference in CYP26B1 was identified as key alteration in migraine. Gene set enrichment analysis identified 88 replicated, significant, exclusively downregulated core pathways, including metabolic, cardiovascular, and immune system-related gene sets and 69 leading genes, like CORIN. Logistic regression of leading genes' and vitamin A pathway-related polymorphisms identified 11 significant polymorphisms in LRP1. Confirmatory analyses excluded a substantial impact of sex, allergy and different vitamin A/retinol intake. Binding simulations and predictions pointed to potential future drug molecules, like tetrandrine and probucol.</p><p><strong>Conclusion: </strong>The replicable transcriptomic map of MO and functional analyses: 1) identified pathomechanisms related to metabolic, cardiovascular and immune system related processes on a molecular level, 2) reported gene level hits, 3) proposed novel potential etiology, like LRP1-induced decreased retinoic acid signaling, and 4) delivered novel drug candidates for the disorder.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"109"},"PeriodicalIF":7.3,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12067696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995500","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 role and interaction of hypothalamic-related neurotransmitters in migraine.","authors":"Ana Belen Salinas-Abarca, Mohammed Gamal-Eltrabily, Marcela Romero-Reyes, Simon Akerman","doi":"10.1186/s10194-025-02044-w","DOIUrl":"https://doi.org/10.1186/s10194-025-02044-w","url":null,"abstract":"<p><p>Migraine is a complex neurological disorder frequently associated with hypothalamic dysfunction. This brain region is essential for maintaining homeostasis due to its regulation of autonomic, endocrine, and circadian systems. While the pathophysiology of migraine remains incompletely understood, clinical features such as the cyclic nature of attacks and symptoms, including nausea, vomiting, yawning, irritability, and sensitivity to light, indicate a significant role for the hypothalamus. Further, potential triggers of migraine, such as stress and disruption to feeding habits, also impact hypothalamic mechanisms. The higher prevalence of migraine in women compared to men suggests a link to hormonal fluctuations involving estrogen, progesterone, and prolactin. These hormones interact with the hypothalamus, potentially influencing the onset and severity of migraine episodes. Additionally, the hypothalamus synthesizes neuropeptides such as orexins, neuropeptide Y, PACAP, oxytocin, and vasopressin, which are all implicated in migraine mechanisms. Understanding the interplay between the hypothalamus, sex hormones, and neuropeptides offers valuable opportunities for endogenous targeted migraine therapies. In this review we discuss hypothalamic contributions to migraine pathophysiology, highlighting the mechanisms affected by hypothalamic connections, neuropeptides, and hormones, and their role as migraine triggers, particularly focusing on factors like stress, fasting, and changes in sleep patterns.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"110"},"PeriodicalIF":7.3,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12067729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983708","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":"Correction: Inhibition of endocannabinoid hydrolases MAGL, FAAH and ABHD6 by AKU‑005 reduces ex vivo cortical spreading depression.","authors":"Flavia Brugia, Konstantin Ivanov, Auni Aroviita, Raisa Giniatullina, Marko Lehtonen, Tarja Malm, Juha Savinainen, Rashid Giniatullin, Adriana Della Pietra","doi":"10.1186/s10194-025-02053-9","DOIUrl":"https://doi.org/10.1186/s10194-025-02053-9","url":null,"abstract":"","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"111"},"PeriodicalIF":7.3,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12067955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997434","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}