Journal of Headache and Pain最新文献

{"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}

{"title":"Altered aminoacid and lipid metabolism in a rat orofacial inflammation model determined by omics approach: potential role in trigeminal sensitisation.","authors":"Krisztina Takács-Lovász, Timea Aczél, Violetta Mohos, Máté Harmath, Jennet Pirkuliyeva, Gellért Karvaly, Róbert Farkas, Michal Ciborowski, Joanna Godzien, Kata Bölcskei, József Kun, Zsuzsanna Helyes","doi":"10.1186/s10194-025-02024-0","DOIUrl":"https://doi.org/10.1186/s10194-025-02024-0","url":null,"abstract":"<p><strong>Background: </strong>Trigeminal activation and sensitisation involved in chronic inflammatory orofacial pain share several similarities with headaches, including migraine. Therefore, understanding the pathophysiological mechanisms is important to determine novel therapies, in which animal models are crucial. Here we aimed to identify key mediators, mechanisms and networks using unbiased multi-omic approaches in a rat orofacial inflammatory pain model.</p><p><strong>Methods: </strong>Complete Freund's Adjuvant (CFA, 50 µl, 1 mg/mL) was injected into the right whisker pad of male Wistar rats (n = 5-11/group), mechanonociceptive threshold was measured by von Frey filaments. Plasma concentrations of metabolites were measured both by targeted (MxP Quant 500 kit) and untargeted mass spectrometry methods on day 3 when maximal facial allodynia developed. Next-generation sequencing of the trigeminal ganglia (TG) was performed, furthermore, transcriptomic and plasma metabolomic data were analysed together.</p><p><strong>Results: </strong>Plasma carnosine, serotonin and fatty acid levels significantly increased, while tryptophan, kynurenine, tyrosine, phenylalanine, asparagine, glycerolipids, and sphingolipids decreased in response to orofacial inflammation. CFA upregulated the Cxcr3 chemokine receptor and downregulated GNRHR in the TG. Bioinformatic analysis revealed altered amino acid metabolism and fatty acid beta-oxidation involved in mitochondrial energy production, neuroinflammation and immune responses.</p><p><strong>Conclusions: </strong>Integrated joint pathway analysis of metabolomic and transcriptomic data provides a useful approach to determine pathophysiological mechanisms of trigeminal sensitization and identify novel drug targets for orofacial pain and headaches.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"108"},"PeriodicalIF":7.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12063288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144021033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Headache-attributed burden and a health-care needs assessment in Delhi and National Capital Region of India: estimates from a cross-sectional population-based study.","authors":"Anand Krishnan, Debashish Chowdhury, Ashish Duggal, Ritvik Amarchand, Andreas Husøy, Timothy J Steiner","doi":"10.1186/s10194-025-02036-w","DOIUrl":"https://doi.org/10.1186/s10194-025-02036-w","url":null,"abstract":"<p><strong>Background: </strong>We have previously shown headache to be highly prevalent in Delhi and National Capital Region of northern India, as we did earlier in Karnataka State in the south. Here we present a complementary study performed contemporaneously of headache-attributed burden, along with a population health-care needs assessment.</p><p><strong>Methods: </strong>In a cross-sectional study using the standardised methodology of the Global Campaign against Headache, we randomly selected households, and one member aged 18-65 years from each, making unannounced visits. Trained interviewers used the HARDSHIP questionnaire incorporating enquiry into various aspects of headache-attributed burden: symptom burden, lost health, impaired participation in daily activities, quality of life (QoL) and willingness to pay (WTP) for treatment. Enquiry included questions about headache yesterday (HY).</p><p><strong>Results: </strong>Of N = 2,066, participants reporting headache in the past year spent 9.5% of their time with headache of moderate intensity (1.8 on the scale of 1-3). Population-level estimates of all time spent with headache were in the range 5.5-6.6%. On this measure, migraine (8.2%) was, at individual level, much more burdensome than tension-type headache (TTH) (1.7%), and females with migraine or TTH were more burdened (8.7% and 2.0% respectively) than males (6.0% and 1.0%). Migraine accounted for substantial health loss (3.6%) at individual level (disability weights from the Global Burden of Disease study factored in), but both measures of overall burden (QoL and WTP) found it greatest among those with probable medication-overuse headache (pMOH) or other causes of headache on ≥ 15 days/month (H15+), with TTH least. For all headache types, participation was more impaired in household than in paid work, the latter being little affected (overall, males 0.3 lost days/month, females 0.1). Impaired participation in social or leisure activities was close to unmeasurably low. Impaired participation from HY was 1.8% across all domains of activity. One quarter (26%) of the population aged 18-65 years would be expected to benefit from health care, meeting our criteria for need: 16.1% with migraine, 6.4% with H15+.</p><p><strong>Conclusion: </strong>Headache disorders in northern India are not only prevalent but also associated with high burden. One quarter of the adult population would benefit from professional headache care.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"106"},"PeriodicalIF":7.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986098","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":"Real-world use of over-the-counter medications by patients with migraine in Japan: results from the OVERCOME (Japan) 2nd study.","authors":"Ryotaro Ishii, Tsubasa Takizawa, Shiho Suzuki, Daisuke Danno, Moemi Miura, Yoshinori Tanizawa, Satoshi Osaga, Chie Hashimoto, Mika Komori","doi":"10.1186/s10194-025-02046-8","DOIUrl":"10.1186/s10194-025-02046-8","url":null,"abstract":"<p><strong>Background: </strong>People with migraine may prefer over-the-counter (OTC) drugs because of multiple reasons, but their overuse can cause medication overuse headaches. This analysis of the ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE (OVERCOME [Japan]) 2nd study describes the real-world use of OTC headache drugs and the challenges that potentially prevent people with migraine from accessing appropriate medical management in Japan.</p><p><strong>Methods: </strong>This analysis of the cross-sectional, population-based, nationwide online survey included adults with migraine. Respondents reported their experiences with prescription and OTC drugs for migraine, migraine-specific drug awareness, and attitude towards migraine. Subgroup analyses were performed based on the number of monthly headache days (MHD) and the frequency of OTC drug use/month.</p><p><strong>Results: </strong>The 19,590 respondents with migraine (68.8% female; mean [SD] age 40.5 [13.1] years) had mean (SD) 3.5 (5.2) MHDs; 29.0% consulted doctors in the past year for migraine. OTC drug use in the past year was common (≥ 62.1%) regardless of doctor consultation or number of MHDs. Among respondents who answered that they would usually use prescribed drugs when they have a migraine attack, 35.2% reported that they would typically use OTC drugs too. The frequency of OTC drug use was the same or higher than that of prescribed drugs in 51.3% of the respondents who consulted doctors in the past year. Only 14.6% of respondents discussed OTC drugs with doctors during consultations in the past year. Migraine-specific drug access and awareness were limited even among frequent OTC drug users (≥ 10 days/month); 18.2% used triptans, but 65.5% never heard of it. Among 37.1% of respondents who had hesitated to visit a doctor, 'I could handle it myself with OTC medicine' was the most common reason for hesitation (34.9%).</p><p><strong>Conclusion: </strong>OTC drug use is common among people with migraine; however, it is not frequently discussed with doctors. Many respondents, even those with frequent OTC drug use, did not have access or awareness of migraine-specific drugs. To prevent medication overuse for migraine, the use of OTC drugs should also be discussed and managed.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"107"},"PeriodicalIF":7.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12056991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029363","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":"Unmasking the relationship between CGRP and glutamate: from peripheral excitation to central sensitization in migraine.","authors":"Fahimeh Martami, Kathleen F Holton","doi":"10.1186/s10194-025-02043-x","DOIUrl":"https://doi.org/10.1186/s10194-025-02043-x","url":null,"abstract":"<p><p>The exact mechanisms that trigger the activation of the trigeminovascular system in migraine remain unclear. The involvement of calcitonin gene-related peptide (CGRP) in migraine is well-documented, and treatments aimed at blocking CGRP activity have proven successful in reducing migraine attacks for some patients. However, around one third of individuals do not respond to these therapies, which are also limited by factors like cost, side effects, and contraindications. There is growing evidence suggesting that glutamate, an excitatory neurotransmitter, plays a crucial role in the onset and maintenance of migraine pain, partially by enhancing CGRP release. Increased glutamate levels have been linked to both peripheral and central sensitization, potentially contributing to the development and persistence of chronic migraine. The relationship between CGRP and glutamate is complex, with glutamate possibly acting as an upstream trigger for CGRP release. This review examines the interplay between CGRP and glutamate, and their involvement in both peripheral and central sensitization. It also explores the therapeutic potential of targeting either glutamate or CGRP, aiming to address both peripheral and central migraine mechanisms. Finally, the role of triggers in migraine initiation at the peripheral level is discussed, offering insights into potential preventive strategies.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"101"},"PeriodicalIF":7.3,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004733","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}