Journal of Headache and Pain最新文献

{"title":"A glutamatergic ventrolateral periaqueductal gray-lateral habenula pathway is associated with depression-like behavioral measures in young adult male mice with trigeminal neuropathic pain.","authors":"Lulu Zhang, Yizhen Yao, Chengmao Zhou, Minhui Wu, Fucheng Zhang, Jiwei Yao, He Zhu","doi":"10.1186/s10194-026-02415-x","DOIUrl":"10.1186/s10194-026-02415-x","url":null,"abstract":"<p><strong>Background: </strong>Depression is a clinically important comorbidity of trigeminal pain disorders, including trigeminal neuralgia, yet the neural circuits linking persistent trigeminal nerve injury to negative affect remain incompletely understood. The present study aimed to investigate the involvement of the ventrolateral periaqueductal gray (vlPAG)-lateral habenula (LHb) pathway in depression-like behavioral measures in a young adult male mouse model of trigeminal neuropathic pain.</p><p><strong>Methods: </strong>A mouse model of trigeminal neuropathic pain was established in young adult male mice using infraorbital nerve chronic constriction injury (IoN-CCI). Spontaneous facial pain-related behavior and depression-like behavioral measures were assessed using facial grooming analysis, the sucrose preference test, the open field test, and the tail suspension test. c-Fos mapping, cell-type analysis, viral tracing, and chemogenetic manipulation of vlPAG glutamatergic neurons and the vlPAG-LHb pathway were performed to examine neuronal recruitment, anatomical connectivity, and behavioral relevance.</p><p><strong>Results: </strong>In young adult male mice, IoN-CCI induced persistent facial grooming behavior as an index of spontaneous facial pain-related behavior and, by 4 weeks after surgery, was associated with depression-like behavioral changes without detectable alterations in body weight, general locomotor activity, or hindpaw mechanical and thermal sensitivity. c-Fos mapping and cell-type analyses showed a progressive increase in c-Fos expression in vlPAG neurons following IoN-CCI, with most labeled neurons identified as glutamatergic, suggesting recruitment of vlPAG glutamatergic neurons in this model. Chemogenetic inhibition of vlPAG glutamatergic neurons decreased depression-like behavioral measures, whereas chemogenetic activation increased these measures, without significantly altering facial grooming behavior used as an index of spontaneous facial pain-related behavior. Viral tracing provided anatomical evidence for a projection from the vlPAG to the LHb, and c-Fos expression in LHb neurons increased following IoN-CCI. Chemogenetic inhibition of the vlPAG-LHb pathway decreased depression-like behavioral measures, whereas chemogenetic activation increased these measures in IoN-CCI mice and was associated with similar behavioral changes in naive mice.</p><p><strong>Conclusion: </strong>These findings suggest that the vlPAG-LHb pathway is functionally associated with behavioral measures related to negative affect in a young adult male mouse model of trigeminal neuropathic pain, providing a circuit-level framework for understanding pain-associated affective disturbances.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13471550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148194822","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":"Central sensitization, work-related stress, and musculoskeletal pain symptoms in desk-based workers with and without migraine: a cross-sectional study.","authors":"Dilara Onan, Pelin Yenilmez Yeşildaş, Merve Ceren Akgör, Doğan Porsnok","doi":"10.1186/s10194-026-02411-1","DOIUrl":"10.1186/s10194-026-02411-1","url":null,"abstract":"<p><strong>Background: </strong>Migraine can impair productivity, work performance, and daily functioning in working-age adults. While higher Central Sensitization Inventory (CSI) scores have been observed in migraine chronicity, work-related stress, and musculoskeletal pain are also common among desk-based workers and may play a role in exacerbating migraine symptoms. However, these factors have rarely been studied together in this population. This cross-sectional study aimed to compare central sensitization, work-related stress, and musculoskeletal pain symptoms in desk-based workers with and without migraine, to examine the relationships among them, and to identify the determinants of central sensitization in individuals with migraine.</p><p><strong>Methods: </strong>This cross-sectional study included 228 desk-based workers: a control group (CG) without migraine (n = 84), episodic migraine (EM) (n = 74), and chronic migraine (CM) (n = 70). Participants completed the CSI, General Work Stress Scale (GWSS), Nordic Musculoskeletal Questionnaire (NMQ), Migraine Disability Assessment (MIDAS), and Headache Impact Test-6 (HIT-6). Group comparisons were performed using ANOVA or Kruskal-Wallis tests. Spearman coefficients were used in correlation analyses. Multiple linear regression was applied to identify factors associated with CSI.</p><p><strong>Results: </strong>Both migraine groups scored higher on the CSI compared to the CG (p < 0.001), with CM showing the highest CSI scores. This difference remained significant after adjusting for confounders. GWSS scores were also higher in both migraine groups than the CG (p < 0.001) and remained significant after adjustment. NMQ;3-items were significantly higher in the migraine groups compared to the CG (p ≤ 0.005), independent of confounders. In the migraine groups, higher CSI scores showed a positive correlation with GWSS, MIDAS, HIT-6, and NMQ. In multiple linear regression analysis, GWSS (β = 0.380), number of painful body regions during the past 12 months (β = 0.382), MIDAS (β = 0.230), and the number of headache days per month (β = 0.170) were identified as variables independently associated with CSI scores (all p < 0.05).</p><p><strong>Conclusions: </strong>Desk-based workers with migraine had higher central sensitization, greater work-related stress, and more widespread musculoskeletal pain symptoms compared to those without migraine. In desk-based workers with migraine, central sensitization was more pronounced in CM than EM, suggesting a potential role in migraine chronicity. These findings support multifaceted management strategies for desk-based workers with migraine, including headache-stress management, musculoskeletal rehabilitation, and Sustainable Development Goal-3, \"to ensure healthy lives and promote well-being for all ages.\"</p><p><strong>Trial registration: </strong>NCT07554664 (registration date: 21.04.2026).</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13422304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148194751","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 effectiveness and safety of CGRP monoclonal antibodies in elderly migraine patients: a Korean multicenter study.","authors":"Soohyun Cho, Mi-Kyoung Kang, Heui-Soo Moon, Mi Ji Lee, Soo-Kyoung Kim, Hong-Kyun Park, Woo-Seok Ha, Min Kyung Chu, Young-Eun Gil, Byung-Su Kim, Soo-Jin Cho","doi":"10.1186/s10194-026-02410-2","DOIUrl":"10.1186/s10194-026-02410-2","url":null,"abstract":"<p><strong>Background: </strong>While calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) have demonstrated significant efficacy in general migraine populations, real-world data specifically focusing on elderly patients remain limited. This multicenter study aimed to evaluate the long-term effectiveness and safety of CGRP mAbs in Korean migraine patients aged 65 and older.</p><p><strong>Methods: </strong>This multicenter, retrospective real-world study analyzed 107 patients aged ≥ 65 years initiated on CGRP mAbs (galcanezumab or fremanezumab) at nine Korean university hospitals between January 2022 and April 2025. Effectiveness was measured by the proportion of patients achieving a ≥ 30%, ≥ 50%, or ≥ 75% reduction in monthly headache days (MHD) at 3, 6, and 12 months. Response rates were reported using an intention-to-treat (ITT) framework in which non-attendees were conservatively classified as non-responders, with the observed-case analysis presented as a sensitivity analysis. Safety was ascertained at each follow-up visit through open-ended clinical interview and patient self-report; adverse events were adjudicated for drug relationship by the treating clinician. Multivariable logistic regression identified independent predictors of ≥ 50% response at 3 months.</p><p><strong>Results: </strong>Of 107 enrolled patients, 103 reached the 3-month time point, 93 reached 6 months, and 61 reached 12 months by the data lock. On an ITT basis, the ≥ 50% response rate was 38.8% (40/103) at 3 months, 40.9% (38/93) at 6 months, and 31.1% (19/61) at 12 months. The corresponding observed-case rates were 48.2%, 67.9%, and 70.4%, respectively. A linear mixed-effects model confirmed a significant reduction in MHD over time (F = 48.912, p < 0.001). Female sex was a significant positive predictor of ≥ 50% response at 3 months (adjusted OR 3.21, 95% CI 1.04-9.93, p = 0.043), while prior failure of OnabotulinumtoxinA was a negative predictor (adjusted OR 0.18, 95% CI 0.03-0.95, p = 0.043). One all-cause death (ruptured dissecting aneurysm) occurred during follow-up and was adjudicated as unrelated to study drug; no other serious adverse events were reported. Documented adverse events were mild and included constipation and injection site reactions.</p><p><strong>Conclusion: </strong>Although long-term follow-up data were available for only a limited number of patients, a substantial proportion of those who continued treatment demonstrated a response of at least 50%. These results imply that CGRP-targeted therapy could be an effective and well-tolerated preventive treatment option for older migraine patients.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13321677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148176132","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 impairs the auditory protective mechanism: a potential biomarker.","authors":"Muchen Huang, Guanxia Xiong, Xianren Wang","doi":"10.1186/s10194-026-02414-y","DOIUrl":"10.1186/s10194-026-02414-y","url":null,"abstract":"<p><strong>Background: </strong>Migraine is a prevalent neurological disorder frequently accompanied by auditory symptoms such as tinnitus and hyperacusis. While their associations suggest shared neural mechanisms, objective evidence regarding the specific involvement of brainstem-mediated auditory efferent pathways in migraine remains limited. The medial olivocochlear reflex (MOCR) and the middle ear muscle reflex (MEMR) are two key auditory protective mechanisms, yet their integrity in migraine patients remains to be investigated. This study aimed to evaluate the functional integrity of the MOCR and MEMR pathways in migraine patients with and without comorbid tinnitus.</p><p><strong>Methods: </strong>In this cross-sectional study, 143 participants were classified into four groups based on strict diagnostic criteria: healthy controls (HC, n = 44), tinnitus-only (T, n = 49), migraine-only (M, n = 25), and migraine with tinnitus (TM, n = 25). Groups were matched for age, sex, and hearing thresholds. All participants underwent comprehensive audiological assessments, including pure-tone audiometry, ipsilateral and contralateral acoustic reflex threshold (ART) testing to assess MEMR function, and distortion-product otoacoustic emissions (DPOAE) with contralateral suppression evaluation to assess MOCR function.</p><p><strong>Results: </strong>The migraine group (M) demonstrated significantly elevated contralateral ART (indicating MEMR impairment) at 500 Hz and 1000 Hz (p < 0.001) and globally reduced DPOAE suppression (reflecting MOCR dysfunction) (p < 0.001) compared to healthy controls. The TM group exhibited a similar pattern of MOCR and MEMR dysfunction to the M group, with no significant additive effect from tinnitus comorbidity. A clear gradient of contralateral ART impairment was observed across groups: HC < T < (M ≈ TM). Ipsilateral ART results showed less consistent abnormalities.</p><p><strong>Conclusion: </strong>Migraine may be associated with specific dysfunction of brainstem auditory efferent pathways, particularly affecting both MOCR and MEMR systems, independent of peripheral hearing status. The convergent abnormalities in migraine patients with and without tinnitus indicate that auditory efferent disruption may be an intrinsic component of migraine pathophysiology. These findings support the potential of contralateral ART as an objective biomarker of migraine-related auditory pathway involvement, highlighting the clinical value of auditory assessment in migraine management and providing insights for the development of targeted therapeutic strategies.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13471409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148176178","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 and menopause as converging factors in brain vulnerability: a hypothesis-driven perspective.","authors":"Parisa Gazerani","doi":"10.1186/s10194-026-02404-0","DOIUrl":"10.1186/s10194-026-02404-0","url":null,"abstract":"<p><p>Migraine is a highly prevalent neurological disorder with a pronounced female predominance, yet its relationship with brain aging remains incompletely understood. Across the female lifespan, migraine interacts with neuroendocrine transitions, particularly menopause, a period characterized by substantial hormonal, metabolic, and neuroimmune changes. This hypothesis-driven narrative perspective synthesizes evidence across clinical, neuroimaging, and mechanistic domains to explore whether migraine, particularly in chronic or hormonally sensitive forms, may reflect altered neural vulnerability in a subset of women across midlife. A conceptual neuroendocrine framework is proposed in which recurrent migraine-related processes, including network stress, neuroinflammatory signaling, and bioenergetic demand, and altered sensory processing, may interact with estrogen-dependent regulatory mechanisms across adulthood. The menopausal transition, characterized by hormonal instability followed by sustained estrogen decline, may represent a period during which previously compensated neural differences become more clinically apparent. Evidence from neuroimaging and biomarker studies suggests partial overlap between migraine-related alterations and biological processes implicated in brain aging; however, findings remain heterogeneous and are not consistently linked to long-term cognitive outcomes. Within this framework, migraine is not interpreted as a deterministic or causal factor in neurodegeneration, but rather as a potential clinical indicator of context-dependent alterations in neural vulnerability influenced by comorbidities, hormonal factors, and individual resilience. The proposed model is exploratory and highlights the need for longitudinal and mechanistic studies to clarify whether migraine-related features have relevance for long-term brain health. By integrating perspectives from neuroscience, endocrinology, and pain research, this work aims to generate testable hypotheses and to support further development of sex-informed approaches to studying brain aging in women.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"27 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13235177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148163342","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 microstructural alterations in episodic cluster headache outside attacks: a tract-based spatial statistics study.","authors":"Francesca Caramia, Antonio Di Renzo, Giada Giuliani, Davide Chiffi, Cherubino Di Lorenzo, Alessio Colangelo, Alessandro De Maio, Luigi Della Volpe, Marco Fiorelli, Giulia Di Stefano, Marta Altieri, Gianluca Coppola","doi":"10.1186/s10194-026-02396-x","DOIUrl":"10.1186/s10194-026-02396-x","url":null,"abstract":"<p><strong>Background: </strong>Cluster headache (CH) is a highly disabling primary headache disorder increasingly conceptualized as a disorder of distributed brain networks rather than an isolated trigeminovascular dysfunction. While structural and functional MRI studies have demonstrated persistent brain alterations outside the ictal phase, the role of white matter microstructural changes supporting network-level dysfunction remains incompletely understood.</p><p><strong>Methods: </strong>We investigated cerebral white matter microstructure in 27 patients with episodic CH examined during the bout outside active attacks using diffusion tensor imaging and tract-based spatial statistics (TBSS). Fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) were compared between patients and healthy controls (N = 20) on a whole-brain white matter skeleton. Associations between diffusion metrics and clinical variables were explored using an ANCOVA-based TBSS framework.</p><p><strong>Results: </strong>Compared with controls, patients with episodic CH showed widespread white matter microstructural alterations, characterized by reduced FA and AD and increased MD in multiple clusters involving long-range associative and projection pathways connecting frontal, parietal, temporal, subcortical, and cerebellar regions. No significant associations were observed between diffusion metrics and clinical variables, including disease duration, attack frequency, and pain intensity.</p><p><strong>Discussion: </strong>White matter alterations predominantly affected pathways supporting large-scale pain-related and cognitive-affective networks, including fronto-parietal, thalamo-cortical, and cerebello-thalamo-cortical connections. These findings are consistent with a network-based model of CH and integrate coherently with recent multimodal MRI evidence of cortical thickness and functional connectivity alterations observed outside attacks in a largely overlapping cohort.</p><p><strong>Conclusions: </strong>Our results provide evidence of persistent white matter microstructural abnormalities in episodic CH outside the ictal phase, supporting the concept of CH as a disorder of distributed brain networks. White matter alterations may represent a structural substrate underlying enduring network dysfunction predisposing patients to recurrent attacks.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13248305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148163358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CGRP-targeted migraine treatment and early pathophysiology in experimental subarachnoid hemorrhage.","authors":"Emelie P Fungbrant, Jesper P Bömers, Philip V Reducha, Spyridoula Kazantzi, Tiit Mathiesen, Lars Edvinsson, Kristian A Haanes","doi":"10.1186/s10194-026-02403-1","DOIUrl":"10.1186/s10194-026-02403-1","url":null,"abstract":"<p><strong>Background: </strong>Calcitonin gene-related peptide (CGRP) is a central mediator in migraine and an endogenous vasodilator in the trigeminovascular system. Its role in subarachnoid hemorrhage (SAH), remains uncertain, particularly in patients receiving CGRP-targeted migraine therapy at the time of hemorrhage. This study examined whether CGRP blockade administered shortly before experimental SAH affects outcome and whether early SAH is associated with altered trigeminovascular CGRP signaling.</p><p><strong>Methods: </strong>CGRP-mediated vasodilation was first assessed ex vivo in rat and mouse cerebral arteries using wire myography to identify the most suitable species for SAH experiments. Experimental pre-chiasmatic SAH was then induced in rats. At 24 h, body weight, rotating pole performance, mechanical sensitivity, and capsaicin evoked CGRP release from dura mater and trigeminal ganglion were evaluated in SAH and sham animals. In a separate intervention arm, rats received vehicle or the anti-CGRP monoclonal antibody fremanezumab, 30 mg/kg intravenously, 15 min before SAH. Functional outcome, neurological scoring, body weight, and survival were followed for 14 days.</p><p><strong>Results: </strong>Rat basilar arteries showed markedly greater CGRP-induced dilation than mouse basilar arteries, supporting rat as the relevant model. At 24 h after SAH, body weight was reduced whereas periorbital and plantar von Frey thresholds were unchanged. Capsaicin-evoked CGRP release from dura mater was significantly reduced after SAH, while trigeminal ganglion release was unaffected, consistent with early peripheral trigeminovascular peptide release. Fremanezumab treated animals showed higher cerebral blood flow 5 min after SAH and improved rotating pole performance at 48 h compared with vehicle treated animals. No significant differences were observed in composite survival, defined as freedom from spontaneous death or euthanasia at humane endpoint, body weight trajectory, well-being score, or composite neurological score at the 14 day follow up.</p><p><strong>Conclusions: </strong>Experimental SAH is associated with early impairment of releasable CGRP in dura mater, supporting acute trigeminovascular involvement after hemorrhage. Pre-existing CGRP blockade did not worsen overall 14-day outcome in this model of SAH, but seemingly improved early functional recovery and the temporal pattern of disease progression. These findings suggest stage-dependent effects of CGRP signaling in SAH and support further study of CGRP-targeted therapies in cerebrovascular disease.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13312570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148055013","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: What's a migraine day? Towards a consensus definition for clinical care and research - a Delphi panel-based study.","authors":"Luna De Loose, Koen Paemeleire, Christina I Deligianni, Christian Lampl, Derya Uluduz, Erling Tronvik, Gianluca Coppola, Henrik Schytz, Jean Schoenen, Margarita Sanchez Del Rio, Paolo Martelletti, Patricia Pozo-Rosich, Raquel Gil-Gouveia, Kristina Ryliskiene, Simona Sacco, Esme Ekizoglu, Igor Petrušić, Rolf Fronczek, Phil Holland, Uwe Reuter, Peter J Goadsby, Antoinette MaassenVanDenBrink, Jan Versijpt","doi":"10.1186/s10194-026-02407-x","DOIUrl":"10.1186/s10194-026-02407-x","url":null,"abstract":"","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"27 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13217784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054929","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":"Trigeminal neuralgia: from clinical challenges to molecular insights.","authors":"Yijia Xu, Yujie Fan, Ruiding Li, Binbin Tan, Bo Li, Jianfang Sun, Shuai Han, Jianqi Wu, Anhua Wu","doi":"10.1186/s10194-026-02408-w","DOIUrl":"10.1186/s10194-026-02408-w","url":null,"abstract":"<p><p>Trigeminal neuralgia (TN) is a paroxysmal, recurrent, electric shock‑ or knife‑like severe pain localized to the sensory distribution of the trigeminal nerve branches in the face. Often referred to as \"the most painful affliction known to humankind\". First-line drugs carbamazepine and oxcarbazepine are associated with long-term side effects and diminishing efficacy, highlighting an urgent need for new therapeutic strategies. This review systematically summarizes the current progress in TN animal models (ranging from chronic constriction and inflammatory models to genetically engineered models), the multi-brain-region interactive pain transmission circuitry, molecular targets (voltage-gated sodium/calcium/potassium channels, TRP channels, chemokines, and epigenetic regulators), and drug development. Current treatments primarily rely on ion channel modulators, while emerging strategies involve Nav1.7/Cav3.2 inhibitors, CGRP antibodies, NRF2 activators, and botulinum toxin. Future efforts should focus on establishing more clinically translational precision models, dissecting the spatiotemporal dynamics of neural circuits, promoting multi-target combination therapies based on molecular subtyping, and accelerating the transition from symptomatic control to curative treatment.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13440117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148055007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and social burden of migraine in Japanese males: a cross-sectional comparison with females without menstrual migraine.","authors":"Tsubasa Takizawa, Keiko Ihara, Reiko Yoshikawa, Kanae Togo, Takahiro Kitano, Masahiro Iijima","doi":"10.1186/s10194-026-02405-z","DOIUrl":"10.1186/s10194-026-02405-z","url":null,"abstract":"<p><strong>Background: </strong>Migraine is globally more prevalent in females; however, the clinical and social burden among males remains insufficiently characterized. This study aimed to describe the clinical features and social burden of migraine in Japanese males to identify sex-specific migraine profiles.</p><p><strong>Methods: </strong>A cross-sectional, population-based web survey was conducted among Japanese adults aged ≥ 18 years diagnosed with migraine according to modified criteria from the International Classification of Headache Disorders, Third Edition (ICHD-3). Participants were grouped by sex; females diagnosed with menstrual migraine (MM) were excluded to minimize hormonal confounding. Key outcomes included pain intensity (Visual Analog Scale [VAS]), pain duration, and social burden assessed using validated instruments: Migraine Interictal Burden Scale (MIBS-4), Migraine Disability Assessment (MIDAS), Migraine-Specific Quality of Life Questionnaire (MSQ), and Work Productivity and Activity Impairment for Migraine (WPAI-M) scores.</p><p><strong>Results: </strong>Of 266,392 individuals screened, 18,750 completed the survey; 4,161 males and 9,997 females (excluding those with MM) were included in the analysis. Males were older (mean± standard deviation age: 43.9 ± 12.4 vs. 40.9 ± 12.2 years) and reported more lifestyle-related triggers (e.g., alcohol, irregular eating, and overexercise). Males, compared to females, experienced greater pain intensity (VAS: 57.1 ± 16.7 vs. 54.9 ± 19.6; p < 0.001) but shorter pain duration (6.3 ± 9.4 vs. 7.9 ± 12.4 h; p < 0.001). MIDAS scores were comparable (6.3 ± 10.8 vs. 6.0 ± 9.6; p = 0.283), while MIBS-4 scores were higher in males (4.0 ± 3.5 vs. 3.3 ± 3.3; p < 0.001). MSQ scores were lower in males for domains of interference (83.5 ± 20.0 vs. 85.4 ± 18.3; p = 0.001) and emotional function (80.2 ± 20.9 vs. 81.8 ± 20.3; p = 0.007). Work-related impairment was more pronounced in males than in females, with higher absenteeism (4.7 ± 14.1 vs. 3.4 ± 12.7; p = 0.001), presenteeism (31.5 ± 22.9 vs. 29.5 ± 23.1; p = 0.007), and overall work impairment (33.6 ± 24.6 vs. 30.9 ± 24.3; p = 0.001). Preventive medication use was higher in males (oral: 40.8% vs. 34.3%; injectables: 3.3% vs. 1.7%).</p><p><strong>Conclusion: </strong>Males with migraine exhibited a greater burden in terms of pain intensity and functional impairment relative to females without MM. These findings support the development of sex-specific and individualized management strategies that incorporate both pharmacological and lifestyle interventions to reduce disease burden and enhance patient-centered care.</p><p><strong>Trial registration: </strong>Not applicable.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13403815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054956","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}