Journal of Headache and Pain最新文献

{"title":"Cold receptor TRPM8 as a target for migraine-associated pain and affective comorbidities.","authors":"David Cabañero, Edward P Carter, Rafael González-Cano, Enrique J Cobos, Asia Fernández-Carvajal, Antonio Ferrer-Montiel","doi":"10.1186/s10194-025-02082-4","DOIUrl":"10.1186/s10194-025-02082-4","url":null,"abstract":"<p><strong>Background: </strong>Genetic variations in the Trpm8 gene that encodes the cold receptor TRPM8 have been linked to protection against polygenic migraine, a disabling condition primarily affecting women. Noteworthy, TRPM8 has been recently found in brain areas related to emotional processing, suggesting an unrecognized role in migraine comorbidities. Here, we use mouse behavioural models to investigate the role of Trpm8 in migraine-related phenotypes. Subsequently, we test the efficacy of rapamycin, a clinically relevant TRPM8 agonist, in these behavioural traits and in human induced pluripotent stem cell (iPSC)-derived sensory neurons.</p><p><strong>Findings: </strong>We report that Trpm8 null mice exhibited impulsive and depressive-like behaviours, while also showing frequent pain-like facial expressions detected by an artificial intelligence algorithm. In a nitroglycerin-induced migraine model, Trpm8 knockout mice of both sexes developed anxiety and mechanical hypersensitivity, whereas wild-type females also displayed depressive-like phenotype and hypernociception. Notably, rapamycin alleviated pain-related behaviour through both TRPM8-dependent and independent mechanisms but lacked antidepressant activity, consistent with a peripheral action. The macrolide ionotropically activated TRPM8 signalling in human sensory neurons, emerging as a new candidate for intervention.</p><p><strong>Significance: </strong>Together, our findings underscore the potential of TRPM8 for migraine relief and its involvement in affective comorbidities, emphasizing the importance of addressing emotional symptoms to improve clinical outcomes for migraine sufferers, especially in females.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"146"},"PeriodicalIF":7.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144368943","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":"Adverse events associated with gepants: a pharmacovigilance analysis based on the FDA adverse event reporting system.","authors":"Qi Song, Siyuan Gao, Yaqian Tan","doi":"10.1186/s10194-025-02091-3","DOIUrl":"10.1186/s10194-025-02091-3","url":null,"abstract":"<p><strong>Background: </strong>Gepants have demonstrated notable benefits in migraine therapy, yet their safety profiles are not thoroughly investigated. This study comprehensively analyzed the adverse event (AE) risk signals of the currently approved gepants using the U.S. Food and Drug Administration Adverse Event Reporting System database, aiming to gain better understanding of their post-marketing safety features and potential risks.</p><p><strong>Methods: </strong>All data of the gepants (rimegepant, atogepant, ubrogepant, and zavegepant) from January 1st 2020 to December 31st 2024 were retrieved from the database. Descriptive analysis was conducted to characterize the features of gepant-associated AEs. Disproportionality analysis and subsequent sensitivity analysis were employed to evaluate the risk signals of the gepants utilizing the algorithms of reporting odds ratio (ROR), proportional reporting ratio (PRR), and information component (IC).</p><p><strong>Results: </strong>A total of 7766 reports of rimegepant, 3672 reports of atogepant, 1958 reports of ubrogepant, and 463 reports of zavegepant were identified after data processing. Most AEs were occurred within 30 days after gepant administration. The integration of disproportionality analysis and sensitivity analysis indicated that \"feeling abnormal\" was the most reported AE of rimegepant (n = 185, 6.81%, ROR₀₂₅ = 6.46, IC₀₂₅ = 2.59, PRR = 7.24, χ² = 998.58), while \"constipation\" was the most common AE of atogepant (n = 288, 16.09%, ROR₀₂₅ = 19.99, IC₀₂₅ = 4.10, PRR = 20.72, χ² = 5418.12). The most prevalent AE of ubrogepant was \"fatigue\" (n = 60, 7.19%, ROR₀₂₅ = 1.88, IC₀₂₅ = 0.84, PRR = 2.38, χ² = 48.82), whereas \"dysgeusia\" was the most frequently observed AE of zavegepant (n = 150, 45.18%, ROR₀₂₅ = 212.07, IC₀₂₅ = 6.10, PRR = 181.96, χ² = 26,975.74). Comparative analysis of AEs revealed that two AEs were shared among all gepants and zavegepant had the largest collection of unique AEs (n = 15).</p><p><strong>Conclusions: </strong>The present pharmacovigilance study systematically revealed the significant risk signals of gepants. The common AEs and unique AEs of the four gepants were also identified and explored. Our results would provide valuable reference for the safe use of gepants, guiding personalized drug selection in clinical practice.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"147"},"PeriodicalIF":7.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475603","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":"Glymphatic dysfunction in classical trigeminal neuralgia: DTI-ALPS index stratification from healthy controls to post-MVD.","authors":"Xiaolin Hou, Bo Wu, Ruxiang Xu, Cheng Yin","doi":"10.1186/s10194-025-02064-6","DOIUrl":"10.1186/s10194-025-02064-6","url":null,"abstract":"<p><strong>Background: </strong>The diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index is a non-invasive marker of glymphatic function. Its relevance in classical trigeminal neuralgia (CTN), postoperative glymphatic changes after microvascular decompression (MVD), and associations with clinical and structural measures remain unclear. This study aimed to evaluate glymphatic dysfunction in CTN, examine postoperative DTI-ALPS alterations, explore correlations with clinical indicators, and assess relationships with hippocampal, amygdala, and ventricular volumes.</p><p><strong>Methods: </strong>Fifty-three unilateral CTN patients undergoing MVD and 47 age- and sex-matched healthy controls (HCs) underwent 3.0 T MRI including DTI and 3D T1-weighted imaging. The DTI-ALPS indices were computed preoperatively and at the 6-month follow-up, with volumes of the bilateral hippocampi, amygdalae, and lateral ventricles also being determined. Clinical variables included pain severity (VAS, BNI scales), neurovascular compression (NVC) grades, disease duration, carbamazepine dosage, psychological status (PHQ-9, GAD-7), and sleep quality (PSQI). Statistical methods included independent and paired t-tests, Pearson's and Spearman's correlation analyses, multivariate regression, and ROC curve analysis.</p><p><strong>Results: </strong>Preoperatively, CTN patients showed significantly lower DTI-ALPS indices compared to healthy controls (HCs) on the left, right, and whole-brain (all p < 0.05). Six months post-MVD, only right-side indices remained reduced (p = 0.044). CTN patients also had smaller hippocampal and amygdala volumes and enlarged lateral ventricles versus HCs (all p < 0.05), with no postoperative recovery (all p > 0.05). Preoperative whole-brain DTI-ALPS indices positively correlated with hippocampal volumes and negatively with lateral ventricular volumes. Multivariate regression identified older age and female sex as predictors of lower DTI-ALPS index. ROC analysis indicated preliminary diagnostic potential for distinguishing CTN from HCs (AUC = 0.609, sensitivity/specificity = 83%).</p><p><strong>Conclusions: </strong>CTN is characterized by persistent glymphatic impairment and structural atrophy-hippocampal and amygdala volume loss with ventricular enlargement-that do not normalize at 6 months post-MVD. Older age and female sex are key modulators of glymphatic dysfunction, while classic clinical indicators show no correlation. Combined DTI-ALPS and volumetric MRI metrics may serve as biomarkers for central nervous system involvement and long-term monitoring in CTN.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"148"},"PeriodicalIF":7.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475604","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":"Abstracts from the 18 th European Headache Congress (EHC) : Rotterdam, The Netherlands. 4-7 December 2024.","authors":"","doi":"10.1186/s10194-025-02062-8","DOIUrl":"10.1186/s10194-025-02062-8","url":null,"abstract":"","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 Suppl 2","pages":"138"},"PeriodicalIF":7.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144368944","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":"Migraine through puberty and menopausal transition-data from the population-based Norwegian Women and Health study (NOWAC).","authors":"Nora Stensland Bugge, Kjersti Grøtta Vetvik, Karl Bjørnar Alstadhaug, Tonje Braaten","doi":"10.1186/s10194-025-02083-3","DOIUrl":"10.1186/s10194-025-02083-3","url":null,"abstract":"<p><strong>Background and purpose: </strong>Migraine considerably affects women during their reproductive years. This cross-sectional study uses data from the Norwegian Women and Health study (NOWAC) and investigates the typical age at migraine onset and cessation in women and assesses how reproductive milestones affect migraine patterns.</p><p><strong>Methods: </strong>4825 women with a history of migraine were included in the study. Participants completed a questionnaire that procured detailed information on their migraine characteristics and reproductive histories.</p><p><strong>Results: </strong>Average ages at migraine onset and cessation were 27.8 and 49.7 years, respectively. Migraine onset after age 50 was reported in 9.2% of the participants. Although 80.7% reported cessation before age 60, 46.3% continued to experience migraines postmenopause. Women with migraine with aura were more likely to report migraine onset before menarche than those with migraine without aura.</p><p><strong>Conclusion: </strong>Migraines usually resolve during the fifth decade of a woman's life and menstruation cessation does not necessarily equate to migraine cessation, as almost half of the women continued to experience migraines postmenopause, and one in five after 60 years. Migraine symptom persistence in a significant proportion of postmenopausal women underscores the need for continued management and research on the factors influencing migraine prevalence in later life stages.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"145"},"PeriodicalIF":7.3,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12180204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336614","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":"Inverse association of obesity with bout periodicity in episodic cluster headache: a multicenter cross-sectional study.","authors":"Byung-Su Kim, Mi Ji Lee, Byung-Kun Kim, Jong-Hee Sohn, Tae-Jin Song, Min Kyung Chu, Soo-Kyoung Kim, Jeong Wook Park, Heui-Soo Moon, Pil-Wook Chung, Soo-Jin Cho","doi":"10.1186/s10194-025-02061-9","DOIUrl":"10.1186/s10194-025-02061-9","url":null,"abstract":"<p><strong>Background: </strong>Cluster headache (CH) is the most painful headache disorder. Despite a large body of evidence on obesity's negative influence on migraine, its impact on cluster headache disease activity remains unexplored. We aimed to determine whether body mass index (BMI) and obesity are associated with lifetime bout occurrence and annual bout frequency in patients with episodic cluster headache (ECH).</p><p><strong>Methods: </strong>The Korean Cluster Headache Registry (KCHR) is a prospective, multicenter registry of consecutive patients with CH over 4 years. This cross-sectional study included 316 eligible patients with ECH, with ≥ 2 years of duration of CH disease and ≥ 2 times of lifetime bout occurrence. Obesity was determined using the Asia-Pacific classification (obese: BMI ≥ 25.0 kg/m²). Bout frequency was defined as an average annual number of bout occurrence: number of lifetime bout occurrence divided by total duration of CH disease. The main outcomes included odds ratios (ORs) of BMI and obesity for quartiles of lifetime bout occurrence and annual bout frequency by performing ordinal logistic regression analysis.</p><p><strong>Results: </strong>The mean (SD) age of the patients was 37 (9.7); 50 (15.8%) were female. The mean (SD) BMI was 23.9 (3.2) kg/m²; 105 (33.2%) were obese. The median (interquartile range) duration of CH disease was 10 (6-16) years; lifetime bout occurrence was 7 (4-12); and annual bout frequency was 0.88 (0.5-1.10). In multivariable adjusted models, OR of BMI (per 1 kg/m²) and the obese group for lifetime bout occurrence were 0.89; 95% CI, 0.84-0.95 and 0.40; 95% CI, 0.23-0.68. Age, BMI, and seasonal propensity were associated factors for annual bout frequency. After multivariable adjustment, BMI and obesity were inversely associated with annual bout frequency (BMI per 1 kg/m² OR: 0.92; 95% CI: 0.86-0.98 and obese OR: 0.52; 95% CI: 0.32-0.86).</p><p><strong>Conclusions: </strong>BMI and obesity were inversely associated with lifetime bout occurrence and annual bout frequency in ECH, suggesting that neurobiological aspects of obesity may suppress cluster bout periodicity.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"144"},"PeriodicalIF":7.3,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12180171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336613","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":"Emerging treatments for chronic neuropathic pain from a cross-disease perspective: developments and applications of nanomaterials.","authors":"Rui Sun, Xiaoqin Zhang, Tao Dou, Zhiyi Xiao, Xiaoran Deng","doi":"10.1186/s10194-025-02081-5","DOIUrl":"10.1186/s10194-025-02081-5","url":null,"abstract":"<p><p>Chronic neuropathic pain (CNP) results from disease or damage within the somatosensory nervous system. It represents a prevalent and challenging form of chronic pain that exerts a severe impact on patients' quality of life. This review aims to synthesize and highlight the current understanding of the mechanisms underlying CNP, as well as the evolving therapeutic landscape. With advancements in research, an increasing number of analgesic targets specific to various disease types are being developed, alongside the emergence of novel nanomaterials for treating chronic pain. In this review, we systematically summarize the applications and potential mechanisms of nanomaterials in treating CNP induced by various diseases, providing new insights for both fundamental research and clinical management of CNP.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"143"},"PeriodicalIF":7.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317103","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":"RAMP1-dependent hormonal regulation of CGRP and its receptor in the trigeminal ganglion.","authors":"Anja Holm, Jacob C A Edvinsson, Diana N Krause, Lars Edvinsson","doi":"10.1186/s10194-025-02071-7","DOIUrl":"10.1186/s10194-025-02071-7","url":null,"abstract":"","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"142"},"PeriodicalIF":7.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317104","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":"Ex vivo stimulation of the trigeminal nucleus caudalis induces peripheral CGRP release in the trigeminal ganglion and reveals a distinct dopamine-endocannabinoid mechanism relevant to migraine.","authors":"Isabella Mai Christiansen, Philip Victor Reducha, Lars Edvinsson, Anja Holm, Kristian Agmund Haanes","doi":"10.1186/s10194-025-02072-6","DOIUrl":"10.1186/s10194-025-02072-6","url":null,"abstract":"<p><strong>Background: </strong>Calcitonin gene-related peptide (CGRP) release from trigeminal structures is central to migraine pathophysiology. This study employed an ex vivo model preserving anatomical continuity between the trigeminal nucleus caudalis (TNC) and trigeminal ganglion (TG) to investigate (1) whether TNC stimulation induces peripheral CGRP release from the TG and (2) the potential involvement of a distinct dopamine-endocannabinoid mechanism.</p><p><strong>Methods: </strong>Tissues were dissected as a single unit and placed in custom 3D-printed chambers, allowing targeted stimulation of either the TNC or the TG while measuring CGRP in both compartments. Pharmacological tools, including capsaicin (TRPV1 agonist), KCl (depolarizing agent), dopamine, and selective enzyme inhibitors or receptor antagonists, were used to elucidate underlying signalling pathways. CGRP levels were quantified via enzyme-linked immunosorbent assay.</p><p><strong>Results: </strong>Stimulation of the TNC elicited a significant rise in CGRP release locally and in the TG compartment, whereas directly stimulating the TG did not trigger CGRP release in the TNC. Subsequent experiments showed that applying dopamine to the TNC further enhanced CGRP release. TRPV1 blockade or pharmacological inhibition of N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD), an enzyme important for anandamide biosynthesis, markedly attenuated dopamine-induced CGRP release, indicating that an endocannabinoid-driven mechanism is involved.</p><p><strong>Conclusion: </strong>Activating the TNC alone was sufficient to evoke CGRP release in the peripheral trigeminal compartment, underscoring a potential central-to-peripheral mechanism that may be relevant to migraine. Moreover, a dopamine-endocannabinoid-TRPV1 axis appears to modulate CGRP signalling in this system, indicating additional complexity and providing potential new strategies for migraine therapy.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"141"},"PeriodicalIF":7.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309997","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: The role of community pharmacists in managing common headache disorders, and their integration within structured headache services: position statement on behalf of the European Headache Federation (EHF) and Lifting The Burden (LTB: the Global Campaign against Headache), with the formal endorsement of the International Pharmaceutical federation.","authors":"Heba BaniHani, Christian Lampl, Antoinette MaassenvandenBrink, Faisal Mohammad Amin, Louise Ninett Carlsen, Gianluca Coppola, Christina Deligianni, Raquel Gil-Gouveia, Philip R Holland, Andreas K Husøy, Rigmor Jensen, Madalena Plácido, Uwe Reuter, Kristina Ryliškienė, Margarita Sanchez Del Río, Henrik Winther Schytz, Erling Tronvik, Jan Versijpt, Timothy J Steiner","doi":"10.1186/s10194-025-02073-5","DOIUrl":"10.1186/s10194-025-02073-5","url":null,"abstract":"","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"139"},"PeriodicalIF":7.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12168334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309996","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}