Journal of Headache and Pain最新文献

{"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}

{"title":"Safety, efficacy, and compliance of moderate-to-high dose eptinezumab and erenumab in chronic migraine patients with medication-overuse headache: an updated systematic review and meta-analysis.","authors":"Nhan Nguyen, Vinh Ho Quang Tri, Vy Nguyen Ngoc Dan, Nghi Bao Tran, Laszlo Olah, Mate Heja","doi":"10.1186/s10194-025-02047-7","DOIUrl":"10.1186/s10194-025-02047-7","url":null,"abstract":"<p><strong>Background: </strong>The use of monoclonal antibodies targeting Calcitonin Gene-Related Peptide (CGRP) is an established treatment for chronic migraine (CM). However, its efficacy in CM patients with medication overuse headache (MOH) remains underexplored, and data on the safety and patient compliance of standard-to-high doses, especially Eptinezumab and Erenumab, over at least three months are limited.</p><p><strong>Objective: </strong>This study aims to evaluate the efficacy and safety of anti-CGRP therapy (Eptinezumab and Erenumab) in CM and MOH patients. Specifically, it assesses changes in monthly migraine days (MMDs) after 12 weeks, risk of treatment-emergent adverse events (TEAEs) leading to discontinuation, serious TEAEs, common adverse effects, and MOH remission at 6 months.</p><p><strong>Methods: </strong>A systematic search of PubMed, Cochrane, and Scopus databases identified randomized controlled trials (RCTs) evaluating standard or high dose anti-CGRP therapy in CM patients strictly with MOH. Studies included were required to report a ≥ 50% reduction in MMDs after ≥ 12 weeks, serious TEAEs, TEAEs leading to discontinuation, common adverse events, and MOH remission at 6 months. Heterogeneity was assessed using I² statistics and a random-effects model.</p><p><strong>Results: </strong>Three RCTs with 769 patients receiving standard-to-high dose anti-CGRP monoclonal antibodies (Eptinezumab and Erenumab) for ≥ 12 weeks were included. Anti-CGRP therapy significantly increased the likelihood of a ≥ 50% reduction in MMDs compared to placebo (OR: 2.43; 95% CI: 1.68-3.51; p < 0.00001). No substantial differences were found in TEAEs leading to discontinuation, nasopharyngitis, upper respiratory tract infections, or serious TEAEs between the anti-CGRP and placebo groups. The likelihood of MOH remission was approximately double in the anti-CGRP group (OR: 1.97; 95% CI: 1.40-2.78; p = 0.0001).</p><p><strong>Conclusion: </strong>Standard-to-high dose anti-CGRP therapies (eptinezumab, erenumab) effectively reduce monthly migraine days and improve MOH remission rates with minimal adverse effects, showing good tolerability in CM patients with MOH.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"99"},"PeriodicalIF":7.3,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12054139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014136","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 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/s10194-025-02021-3","DOIUrl":"https://doi.org/10.1186/s10194-025-02021-3","url":null,"abstract":"<p><p>In the sustainable development goals (SDG) context of seeking universal health coverage, the expanding gap between the supply of specialized and primary health-care providers of headache-related health care and the care needs of the very large number of people affected by headache is a formidable but not insoluble public-health challenge. Structured headache services provide a cost-effective framework wherein controlled patient flows enable the care needs of people with headache to be met at appropriate levels, but these services may still be overwhelmed by inappropriate demand.Community pharmacists are an underutilized resource, potentially well able to provide the solution. To do so, they must, as a profession, be integrated into structured headache services.What remains to be determined is how to achieve this integration in an encouraging climate for change, which recognises the potential for relieving strained health-care systems and meeting a range of health-care needs by expanding pharmacists' scope of practice.This position statement on behalf of the European Headache Federation (EHF) and Lifting The Burden (LTB) is formally endorsed by the International Pharmaceutical Federation (FIP).</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"100"},"PeriodicalIF":7.3,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12054158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999584","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":"Efficacy of monoclonal antibodies against CGRP in migraine patients with fibromyalgia comorbidity: a retrospective monocentric observational study.","authors":"Marina de Tommaso, Stefania Scannicchio, Giulia Paparella, Livio Clemente, Giuseppe Libro","doi":"10.1186/s10194-025-02034-y","DOIUrl":"https://doi.org/10.1186/s10194-025-02034-y","url":null,"abstract":"<p><strong>Background: </strong>Migraine is a common comorbidity with fibromyalgia (FM). CGRP is a potent inflammatory neuropeptide that may play a role in somatic and visceral pain either inflammatory or neuropathic. Previous studies have reported a significant number of migraine patients with FM responding to anti-CGRP therapies. The potential impact on diffuse pain and global disability associated with fibromyalgia is still unclear. In this retrospective, observational, cross-sectional study, we aimed to analyze the effects of a monoclonal antibody therapy in a subpopulation of migraineurs with FM compared to patients without this comorbidity by assessing the headache frequency and disability as well as the severity of FM (assessed by the Fibromyalgia Impact Questionnaire (FIQ).</p><p><strong>Methods: </strong>Among 1088 patients came for the first visit to our headache Center between January 1, 2021, and December 31, 2022, we examined six-month outcomes of 148 migraine patients prescribed various monoclonal antibodies to CGRP, erenumab, galcanezumab, and fremanezumab. One hundred and twenty-two patients were selected, 26 of whom suffered from FM. We retrospectively evaluated the following characteristics at baseline (T0) and after 6 months (T1),headache frequency and severity, number of days with symptomatic medication, and MIDAS score. In the FM patients, we evaluated the FIQ and the intensity of somatic pain using a numerical rating scale from 0 to 10.</p><p><strong>Results: </strong>Headache characteristics improved similarly in patients with and without FM comorbidity. The number of patients in whom headache frequency decreased by at least 50% was similar in the two migraine groups. In patients with FM, both fibromyalgia-related disability and somatic pain improved. The improvement in fibromyalgia disability was significantly correlated with the improvement in migraine-related disability.</p><p><strong>Conclusions: </strong>We found that in migraine suffereres with FM, anti-CGRP monoclonal antibodies had a similar beneficial effect on migraine as in non-fibromyalgia patients, in addition to reducing somatic pain and global disability from the disease. The anti-CGRP agents, represent a good option for the treatment of migraineurs with fibromyalgia, for which no resolutive therapy is yet available.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"102"},"PeriodicalIF":7.3,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022444","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":"Lateral habenula-rostromedial tegmental nucleus circuit mediates inflammatory pain in mice.","authors":"Yanfei Sun, Jing Cao, Chunpeng Xu, Jiangtao Sun, Xiaofeng Liu, Zhenguang Shi, SiMeng An, Danyang Zhao, Dongjie Sun, Xuxin Wang, Guoyan Zhao, Chi Zhang, Guangjian Li, Jinyu Xiao, Jing Yang, Hua Zhao","doi":"10.1186/s10194-025-02052-w","DOIUrl":"https://doi.org/10.1186/s10194-025-02052-w","url":null,"abstract":"<p><strong>Background: </strong>The monoamine system, particularly the serotonergic neurons in the dorsal raphe nucleus (DRN), associated with the synthesis and release of 5-hydroxytryptamine, is crucial for regulating pain. The lateral habenula (LHb) modulates DRN neurons by acting through GABAergic neurons located in the rostromedial tegmental nucleus (RMTg). However, the role of RMTg in mediating the LHb and regulating pain remains unclear. Thus, we aimed to assess the role of the LHb-RMTg pathway in inflammatory pain.</p><p><strong>Methods: </strong>Male C57BL/6 mice were used in the chemogenetic experiments, while male and female Vglut2-ires-cre mice were used in the optogenetic experiments; in both experiments, inflammatory pain model and control groups were established. We performed the Hargreaves and Von Frey tests to assess nociceptive behavior as well as immunohistochemistry staining after chemogenetic activation experiments. Statistical analyses were performed using a t-test, one-way analysis of variance (normally distributed data) or Kruskal-Wallis test (non-normally distributed data) and two-way analysis of variance.</p><p><strong>Results: </strong>Chemogenetic activation/inhibition of RMTg-projecting LHb excitatory neurons was sufficient to decrease or increase heat sensitivity thresholds. Additionally, inhibition of the LHb-RMTg circuit reversed the decreased heat sensitivity thresholds under inflammatory pain conditions using chemogenetic and optogenetic approaches. However, this circuit did not affect mechanical allodynia thresholds, and chemogenetic activation of the circuit decreased c-Fos immunoreactivity in the DRN.</p><p><strong>Conclusions: </strong>Our results indicate that activating glutamatergic neurons within the LHb heightens pain sensitivity by triggering GABAergic neurons in the RMTg, which in turn influences neuronal activity in the DRN. This research offers fresh perspectives on the pain mechanism, potentially revealing new therapeutic avenues for managing inflammatory pain.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"105"},"PeriodicalIF":7.3,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975295","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 burden of migraine and predictions in the Asia-Pacific region, 1990-2021: a comparative analysis of China, South Korea, Japan, and Australia.","authors":"Yun-Xia Wang, Guang-Shuang Lu, Jin-Jing Zhao, Wei Dai, Na Zheng, Guo-En Yao, Ruo-Zhuo Liu","doi":"10.1186/s10194-025-02048-6","DOIUrl":"https://doi.org/10.1186/s10194-025-02048-6","url":null,"abstract":"<p><strong>Background: </strong>Migraine is a leading cause of disability worldwide, significantly impacting quality of life and healthcare systems. Despite its high prevalence and burden, migraine remains underprioritized in global health policies. This study examines the epidemiological trends of migraine in Australia, China, Japan, and South Korea from 1990 to 2021, highlighting regional disparities and forecasting future burdens.</p><p><strong>Methods: </strong>This study utilized data from the Global Burden of Disease (GBD) 2021 to analyze incidence, prevalence, and years lived with disability (YLDs) of migraine. Age-standardized rates (ASRs) were calculated to enable fair cross-country comparisons. Joinpoint regression analysis was applied to assess temporal trends, while Bayesian age-period-cohort (BAPC) modeling was used to project future trends until 2050. Additionally, decomposition analysis was conducted to differentiate the effects of population aging, growth, and epidemiological changes.</p><p><strong>Results: </strong>In 2021, China had the highest migraine burden, with 13.05 million new cases and 184.75 million prevalent cases, followed by Australia, Japan, and South Korea. Incidence rates peaked in adolescence (10-14 years), while prevalence and disability were highest in middle-aged women (40-44 years). From 1990 to 2021, Australia exhibited stable trends, China experienced increasing burden, Japan saw a decline due to aging, and Korea exhibited mixed patterns influenced by opposing demographic and epidemiological forces. Future projections suggest a stable trend in Australia, declining incidence in China and Japan, and continued burden in Korea.</p><p><strong>Conclusion: </strong>Migraine remains a significant public health challenge across all four countries, with age, gender, and demographic changes playing key roles in burden variations. The study highlights the need for region-specific healthcare strategies and age- and gender-sensitive interventions. Future research should explore socioeconomic, behavioral, and healthcare access factors to refine migraine management strategies.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"104"},"PeriodicalIF":7.3,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020929","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":"Who is the patient with resistant myofascial temporomandibular disorders pain? A somatosensory, psychosocial, and genetic characterization.","authors":"Giancarlo De la Torre Canales, Rodrigo Lorenzi Poluha, Flávia Fonseca Carvalho Soares, Dyna Mara Araújo Oliveira Ferreira, Alfonso Sánchez-Ayala, Leonardo Rigoldi Bonjardim, Malin Ernberg, Paulo César Rodrigues Conti","doi":"10.1186/s10194-025-02055-7","DOIUrl":"https://doi.org/10.1186/s10194-025-02055-7","url":null,"abstract":"<p><strong>Background: </strong>Resistance to treatments have been assessed in chronic conditions such as migraine, but not in temporomandibular disorders (TMD). This study aimed to identify factors that influence treatment outcome in patients with myofascial TMD pain.</p><p><strong>Methods: </strong>Seventy-two females were divided into three groups: TMD successfully treated (TMD-S, n = 24), TMD resistant to treatment (TMD-R, n = 24) and Controls without TMD (n = 24). Criteria for resistance included: less than 30% pain reduction after three months of conservative treatment and an average pain intensity > 50 mm (VAS) during the last month. Quantitative sensory testing (QST), psychosocial status and genetic polymorphisms were examined. ANOVA on ranks (psychosocial variables) with Dunn's test as post-hoc or ANOVA (age and somatosensory variables) with Tukey test as post-hoc test, and Dwass-Steel-Critchlow-Fligner test (genetic variables) were used for univariate groups comparisons. Multivariate statistics were used to identify outcomes that separated the groups.</p><p><strong>Results: </strong>QST assessment revealed lower baseline pressure pain threshold and higher wind-up ratio in the trigeminally and spinally innervated areas in the TMD-R group compared with the other groups (p = 0.01). Also, the TMD-R group presented higher values in all assessed psychosocial variables (p < 0.01) and higher prevalence of the HTR1A polymorphism rs6295 (p = 0.02) compared with the other groups at baseline. Multivariate analysis showed that the three variables that distinguished the best between TMD-R and TMD-S were sleeping quality, central sensitization, and depressive symptoms.</p><p><strong>Conclusion: </strong>Psychosocial, somatosensory, and genetic alterations are related to unsuccessful treatment response in myofascial TMD patients.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"98"},"PeriodicalIF":7.3,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12054165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983709","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":"Unveiling new insights into migraine risk stratification using machine learning models of adjustable risk factors.","authors":"Yu-Chen Liu, Ye-Hai Liu, Hai-Feng Pan, Wei Wang","doi":"10.1186/s10194-025-02049-5","DOIUrl":"https://doi.org/10.1186/s10194-025-02049-5","url":null,"abstract":"<p><strong>Background: </strong>Migraine ranks as the second-leading cause of global neurological disability, affecting approximately 1.1 billion individuals worldwide with severe quality-of-life impairments. Although adjustable risk factors-including environmental exposures, sleep disturbances, and dietary patterns-are increasingly implicated in pathogenesis of migraine, their causal roles remain insufficiently characterized, and the integration of multimodal evidence lags behind epidemiological needs.</p><p><strong>Methods: </strong>We developed a three-step analytical framework combining causal inference, predictive modeling, and burden projection to systematically evaluate modifiable factors associated with migraine. First, two-sample mendelian randomization (MR) assessed causality between five domains (metabolic profiles, body composition, cardiovascular markers, behavioral traits, and psychological states) and the risk of migraine. Second, we trained ensemble machine learning (ML) algorithms that incorporated these factors, with Shapley Additive exPlanations (SHAP) value analysis quantifying predictor importance. Finally, spatiotemporal burden mapping synthesized global incidence, prevalence, and disability-adjusted life years (DALYs) data to project region-specific risk and burden trajectories through 2050.</p><p><strong>Results: </strong>MR analyses identified significant causal associations between multiple adjustable factors (including overweight, obesity class 2, type 2 diabetes [T2DM], hip circumference [HC], body mass index [BMI], myocardial infarction, and feeling miserable) and the risk of migraine (P < 0.05, FDR-q < 0.05). The Random Forest (RF)-based model achieved excellent discrimination (Area under receiver operating characteristic curve [AUROC] = 0.927), identifying gender, age, HC, waist circumference [WC], BMI, and systolic blood pressure [SBP] as the predictors. Burden mapping projected a global decline in migraine incidence by 2050, yet persistently high prevalence and DALYs burdens underscored the urgency of timely interventions to maximize health gains.</p><p><strong>Conclusions: </strong>Integrating causal inference, predictive modeling, and burden projection, this study establishes hierarchical evidence for adjustable migraine determinants and translates findings into scalable prevention frameworks. These findings bridge the gap between biological mechanisms, clinical practice, and public health policy, providing a tripartite framework that harmonizes causal inference, individualized risk prediction, and global burden mapping for migraine prevention.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"103"},"PeriodicalIF":7.3,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975301","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":"Inhibition of S100A4 decreases neurotoxic astrocyte reactivity and attenuates neuropathic pain via the TLR4/NF-κB pathway in a rat model of spinal nerve ligation.","authors":"Tao Xue, Yu Song, Jie Zhao, Guiyong Fan, Zhiyuan Liu","doi":"10.1186/s10194-025-02045-9","DOIUrl":"https://doi.org/10.1186/s10194-025-02045-9","url":null,"abstract":"<p><p>S100A4 participates in inflammation and immune reactions in the central nervous system and is involved in the pathogenesis of multiple neurological disorders. It can affect the functions of astrocytes, microglia, infiltrating cells and neurons and further modulates neuronal plasticity and survival in the central nervous system. However, its impact on astrocyte phenotypes and neuropathic pain and the intrinsic mechanisms involved remain poorly understood. Here, we showed that S100A4 was markedly upregulated after spinal nerve ligation and was mainly expressed in neurons in the spinal dorsal horn. Transcriptional inhibition of S100A4 with niclosamide attenuated neuropathic pain after surgery. We found that astrocytes differentiated into C3-positive reactive populations, so-called neurotoxic (A1) astrocytes and identified differentially expressed genes and specific molecular expression signatures after ligation. Neurotoxic astrocyte reactivity is regulated by exogenous S100A4 in vitro, and targeted inhibition of S100A4 suppresses neurotoxic astrocyte proliferation in rats. Finally, we reported that TLR4/NF-κB signaling pathway is a downstream of S100A4 activation, and that specific depletion this pathway suppresses deleterious A1 astrocyte activation and further attenuates the development and maintenance of neuropathic pain after spinal nerve ligation. Thus, S100A4 in neurons plays a key role in neurotoxic astrocyte reactivity and can be targeted for treatment to prevent and alleviate neuropathic pain.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"97"},"PeriodicalIF":7.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12044810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014131","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":"Tolerability of repetitive dihydroergotamine infusions paired with an adjustment in preventive treatment strategy in chronic headache disorders in children and youth.","authors":"Sara Pavitt, Cynthia Morris, Lauren Shin, Andrew Jones, Beata Vayngortin, Natalia Zorrilla, Chengshi Jin, Isabel Allen, Amy A Gelfand","doi":"10.1186/s10194-025-02035-x","DOIUrl":"https://doi.org/10.1186/s10194-025-02035-x","url":null,"abstract":"<p><strong>Background: </strong>In adults, intravenous (IV) dihydroergotamine (DHE) has been shown to be effective at improving medium term outcomes in patients with chronic headache disorders. The IV formulation is utilized given its superior bioavailability. We aim to assess the safety and effectiveness of repetitive IV DHE infusions paired with an adjustment of a preventive treatment strategy within children and youth with chronic headache disorders.</p><p><strong>Methods: </strong>A retrospective chart review was conducted of children and youth diagnosed with a chronic headache disorder who were admitted for DHE from January 2014 - October 2020. Patients completed a 5-day, standardized protocol. A new preventive was started one week after discharge. Data were collected from pre- and post-admission clinic notes. Safety and tolerability were assessed. Results were evaluated using descriptive statistics and compared with paired t-tests.</p><p><strong>Results: </strong>One hundred and eighty-seven patients were included for review. Sixty-eight percent (127) had chronic migraine (CM), 20% (37) new daily persistent headache (NDPH) and 12% (23) persistent headache attributed to head trauma (PHHT). The median (range) age was 16 years (7-21), and median (range) number of previous preventive trials was 4 (0-21). At follow-up, patients with CM had a significant decrease in headache days per month from 28.6 to 26.3 days (95% CI -4.1 to -1.3) p < 0.001, baseline headache intensity decreased from 5.9/10 to 5.3/10 (95% CI -1.3 to -0.1) p = 0.006, number of severe headache days per month decreased from 11.5 to 7.9 days (95% CI -6.5 to -2.3), p < 0.001, and monthly days of acute medication use from 12.1 to 9.8 days (95% CI -4.5 to -0.7) p = 0.002. In patients with NDPH there were significant decreases in baseline headache intensity from 6.4/10 to 5.3/10 (95% CI -1.7 to -0.3) p = 0.005 and monthly days of acute medication usage from 9.2 days to 5.9 days (95% CI -7.8 to -0.1) p = 0.043. Patients with PHHT had a significant decrease in headache days per month from 29 to 24 days (95% CI -9.4 to -0.7) p = 0.031. The most common side effects were nausea (85%) and mild leg cramping (60%).</p><p><strong>Conclusion: </strong>Repetitive DHE infusions followed by preventive treatment adjustment was well tolerated and significantly reduced headache frequency, baseline intensity, number of severe days and/or acute medication usage in children and youth with refractory headache disorders.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"93"},"PeriodicalIF":7.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12042534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143996244","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}