Journal of Headache and Pain最新文献

{"title":"Prediction of new-onset migraine using clinical-genotypic data from the HUNT Study: a machine learning analysis.","authors":"Fahim Faisal, Antonios Danelakis, Marte-Helene Bjørk, Bendik Winsvold, Manjit Matharu, Parashkev Nachev, Knut Hagen, Erling Tronvik, Anker Stubberud","doi":"10.1186/s10194-025-02014-2","DOIUrl":"10.1186/s10194-025-02014-2","url":null,"abstract":"<p><strong>Background: </strong>Migraine is associated with a range of symptoms and comorbid disorders and has a strong genetic basis, but the currently identified risk loci only explain a small portion of the heritability, often termed the \"missing heritability\". We aimed to investigate if machine learning could exploit the combination of genetic data and general clinical features to identify individuals at risk for new-onset migraine.</p><p><strong>Method: </strong>This study was a population-based cohort study of adults from the second and third Trøndelag Health Study (HUNT2 and HUNT3). Migraine was captured in a validated questionnaire and based on modified criteria of the International Classification of Headache Disorders (ICHD) and participants underwent genome-wide genotyping. The primary outcome was new-onset migraine defined as a change in disease status from headache-free in HUNT2 to migraine in HUNT3. The migraine risk variants identified in the largest GWAS meta-analysis of migraine were used to identify genetic input features for the models. The general clinical features included demographics, selected comorbidities, medication and stimulant use and non-headache symptoms as predictive factors. Several standard machine learning architectures were constructed, trained, optimized and scored with area under the receiver operating characteristics curve (AUC). The best model during training and validation was used on unseen test sets. Different methods for model explainability were employed.</p><p><strong>Results: </strong>A total of 12,995 individuals were included in the predictive modelling (491 new-onset cases). A total of 108 genetic variants and 67 general clinical variables were included in the models. The top performing decision-tree classifier achieved a test set AUC of 0.56 when using only genotypic data, 0.68 when using only clinical data and 0.72 when using both genetic and clinical data. Combining the genotype only and clinical data only models resulted in a lower predictivity with an AUC of 0.67. The most important clinical features were age, marital status and work situation as well as several genetic variants.</p><p><strong>Conclusion: </strong>The combination of genotype and routine demographic and non-headache clinical data correctly predict the new onset of migraine in approximately 2 out of 3 cases, supporting that there are important genotypic-phenotypic interactions partaking in the new-onset of migraine.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"70"},"PeriodicalIF":7.3,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Limbic system abnormalities in episodic cluster headache: a 7T MRI multimodal study.","authors":"Xinyu Wang, Luhua Zhang, Yongqin Xiong, Mengmeng Hou, Shuhua Zhang, Caohui Duan, Song Wang, Xiaoyu Wang, Haoxuan Lu, Jiayu Huang, Yan Li, Zhixuan Li, Zhao Dong, Xin Lou","doi":"10.1186/s10194-025-02009-z","DOIUrl":"10.1186/s10194-025-02009-z","url":null,"abstract":"<p><strong>Background: </strong>Although the limbic system has long been thought to be involved in the pathophysiology of cluster headache, inconsistencies in imaging studies of episodic cluster headache (eCH) patients and limited understanding of the specific regions within the limbic system have prevented a full explanation of its involvement in the disease. Therefore, we performed multimodal imaging analysis using 7 T MRI with the aim of exploring structural-functional abnormalities in subregions of the limbic system and their relationship with clinical features.</p><p><strong>Methods: </strong>In this cross-sectional study, we employed 7T MRI to investigate structural (volumetric) and functional (fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo)) alterations in limbic subregions (hypothalamus, thalamus, amygdala, hippocampus) among 69 in-bout but outside the attacks eCH patients and 63 healthy controls (HCs). Automated volumetry and resting-state functional MRI analyses were performed after adjusting for age, Generalized Anxiety Disorder scale, sex (and intracranial volume when evaluating volumetric measures). Then functional-structural coupling indices were computed to assess network-level relationships.</p><p><strong>Results: </strong>In eCH patients, volumes in right anterior inferior and right posterior of hypothalamus, left molecular_layer_hippocampal-head, left lateral-nucleus and left Central-nucleus on the headache side, as well as left tuberal inferior and left tuberal superior of hypothalamus, and right parasubiculum on the contralateral side were significantly altered compared with HCs (P < 0.05). Additionally, the volume of the right anterior inferior was positively correlated with the duration of last headache episode. After false discovery rate correction, widespread alterations in fALFF and ReHo values were observed among hypothalamic, thalamic, hippocampal, and amygdalar subregions, some of which correlated with clinical measures. Furthermore, the structure-function coupling indices in the right anterior inferior and the left lateral geniculate nucleus on the headache side differed significantly between eCH patients and HCs.</p><p><strong>Conclusions: </strong>Our findings demonstrate that in-bout but outside the attacks eCH patients present anatomical and functional maladaptation of the limbic system. Moreover, the observed dissociation between localized abnormalities and largely preserved network coupling-except in the hypothalamus and thalamus-suggests that these two regions may be particularly susceptible to eCH-related dysfunction, while broader brain networks retain compensatory capacity in pathological states. These findings refine potential neuromodulation targets and highlight the value of ultrahigh-field imaging in eCH research.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"69"},"PeriodicalIF":7.3,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations between personality traits and pain experiences in trigeminal neuralgia.","authors":"Jeong-A Lee, Yoon Kyung Han, Won Je Jung, Byung H Lee, Seunghoon Lee","doi":"10.1186/s10194-025-02010-6","DOIUrl":"10.1186/s10194-025-02010-6","url":null,"abstract":"<p><strong>Background: </strong>Pain is influenced by many factors such as personality traits and nociceptive stimuli. This study identified personality traits in patients with trigeminal neuralgia (TN) and investigated the relationships between personality traits and pain perception, pain acceptance, anxiety, and depression.</p><p><strong>Methods: </strong>From March to June 2024, the personality traits of 50 patients with TN and 50 healthy controls (HC) were measured using the 50-item International Personality Item Pool representation of Goldberg markers for the Big-Five factor structure. Patients' pain perception, pain acceptance, anxiety, and depression were measured.</p><p><strong>Results: </strong>The mean neuroticism scores and median anxiety and depression scores of patients with TN were higher than those of HC (p = 0.006, p < 0.001, and p = 0.010). There were no significant differences in pain perception and pain acceptance according to the personality traits. The higher the neuroticism score, the higher the anxiety and depression scores (ρ = 0.437, p = 0.002 and ρ = 0.344, p = 0.014). The higher the anxiety score, the higher the pain catastrophizing score, and the lower the pain acceptance score (ρ = 0.488, p < 0.001 and ρ = -0.365, p = 0.009). Higher depression score was associated with a pain frequency of 11 or more times per 24 h (odds ratio = 1.243, p = 0.015). The higher the depression score, the lower was the pain acceptance score (ρ = -0.324, p = 0.022).</p><p><strong>Conclusions: </strong>In patients with TN, neuroticism was not associated with pain. However, higher levels of neuroticism were associated with higher levels of anxiety and depression, and higher levels of anxiety and depression were associated with higher pain catastrophizing or pain frequency, and lower pain acceptance. These results can be used to establish individualized treatments for patients with TN, that focus on their emotional states according to personality traits, such as adapting psychological therapies differently for individuals with high neuroticism.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"68"},"PeriodicalIF":7.3,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial neural networks applied to somatosensory evoked potentials for migraine classification.","authors":"Gabriele Sebastianelli, Daniele Secci, Francesco Casillo, Chiara Abagnale, Cherubino Di Lorenzo, Mariano Serrao, Shuu-Jiun Wang, Fu-Jung Hsiao, Gianluca Coppola","doi":"10.1186/s10194-025-01989-2","DOIUrl":"10.1186/s10194-025-01989-2","url":null,"abstract":"<p><strong>Background: </strong>Finding a biomarker to diagnose migraine remains a significant challenge in the headache field. Migraine patients exhibit dynamic and recurrent alterations in the brainstem-thalamo-cortical loop, including reduced thalamocortical activity and abnormal habituation during the interictal phase. Although these insights into migraine pathophysiology have been valuable, they are not currently used in clinical practice. This study aims to evaluate the potential of Artificial Neural Networks (ANNs) in distinguishing migraine patients from healthy individuals using neurophysiological recordings.</p><p><strong>Methods: </strong>We recorded Somatosensory Evoked Potentials (SSEPs) to gather electrophysiological data from low- and high-frequency signal bands in 177 participants, comprising 91 migraine patients (MO) during their interictal period and 86 healthy volunteers (HV). Eleven neurophysiological variables were analyzed, and Principal Component Analysis (PCA) and Forward Feature Selection (FFS) techniques were independently employed to identify relevant variables, refine the feature space, and enhance model interpretability. The ANNs were then trained independently with the features derived from the PCA and FFS to delineate the relationship between electrophysiological inputs and the diagnostic outcome.</p><p><strong>Results: </strong>Both models demonstrated robust performance, achieving over 68% in all the performance metrics (accuracy, sensitivity, specificity, and F1 scores). The classification model trained with FFS-derived features performed better than the model trained with PCA results in distinguishing patients with MO from HV. The model trained with FFS-derived features achieved a median accuracy of 72.8% and an area under the curve (AUC) of 0.79, while the model trained with PCA results showed a median accuracy of 68.9% and an AUC of 0.75.</p><p><strong>Conclusion: </strong>Our findings suggest that ANNs trained with SSEP-derived variables hold promise as a noninvasive tool for migraine classification, offering potential for clinical application and deeper insights into migraine diagnostics.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"67"},"PeriodicalIF":7.3,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788515","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: Combining treatments for migraine prophylaxis: the state‑of‑the‑art.","authors":"Lanfranco Pellesi, David Garcia-Azorin, Eloisa Rubio-Beltrán, Wook-Seok Ha, Roberta Messina, Raffaele Ornello, Igor Petrusic, Bianca Raffaelli, Alejandro Labastida-Ramirez, Ruth Ruscheweyh, Claudio Tana, Doga Vuralli, Marta Waliszewska-Prosół, Wei Wang, William Wells-Gatnik","doi":"10.1186/s10194-025-02007-1","DOIUrl":"10.1186/s10194-025-02007-1","url":null,"abstract":"","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"66"},"PeriodicalIF":7.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780261","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":"Is migraine a common manifestation of CADASIL? Arguments Pros.","authors":"Hugues Chabriat","doi":"10.1186/s10194-025-01980-x","DOIUrl":"10.1186/s10194-025-01980-x","url":null,"abstract":"<p><strong>Background: </strong>Migraine with aura (MA) is a hallmark feature of CADASIL, a hereditary small-vessel disease caused by NOTCH3 mutations. While MA is prevalent in CADASIL, its underlying mechanisms remain unclear, and the links observed can be questioned or debated. This study examined the prevalence, clinical characteristics, and pathophysiology of MA in patients with CADASIL.</p><p><strong>Methods: </strong>Clinical and experimental data were reviewed to assess MA prevalence, aura characteristics, sex differences, and pathophysiological insights from CADASIL models to confirm the indisputable pathophysiological links between migraine and aura and this unique genetic model of cerebral small vessel disease.</p><p><strong>Results: </strong>MA was 10-20 times more prevalent in patients with CADASIL than in the general population, with frequent atypical and prolonged auras. The altered sex distribution and delayed onset suggest disease-specific mechanisms. Experimental data also revealed heightened susceptibility to cortical spreading depression (CSD) in preclinical CADASIL models, linked to greater fragility in maintaining cortical ionic homeostasis.</p><p><strong>Conclusion: </strong>The high prevalence and distinct MA features, as well as the data obtained at the preclinical level, strongly support a causal relationship mediated by neurovascular dysfunction in CADASIL. Accumulating data in this condition sheds new light on the much-debated relationship between migraine and cerebrovascular diseases.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"64"},"PeriodicalIF":7.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11963349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763840","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":"Is migraine a common manifestation of CADASIL-Cons.","authors":"Yen-Feng Wang","doi":"10.1186/s10194-025-01981-w","DOIUrl":"10.1186/s10194-025-01981-w","url":null,"abstract":"<p><p>Headaches and transient neurological symptoms that bear resemblances to clinical manifestations of migraine, especially migraine with aura, are common among patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) or cysteine-altering NOTCH3 genetic variants. However, according to the International Classification of Headache Disorders, Third Edition (ICHD-3), these patients should be diagnosed as headache attributed to cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) rather than migraine with or without aura. Although transient focal neurological symptoms are often labeled as migraine aura, these symptoms are often atypical and complicated, and could not easily conform to the criteria for migraine with aura. Besides, the association between migraine and CADASIL could not be supported by population-based genetic studies, and cysteine-altering NOTCH3 genetic variants are not more common among patients with migraine with or without aura compared with non-migraine controls. In addition, the underlying pathophysiology may be different between migraine and CADASIL. Although increased cortical spreading depression (CSD) susceptibility in mice harboring a human pathogenic Notch3 variant is often regarded as supportive evidence for the association, CSD could been seen in conditions other than migraine, such as cerebral ischemia. The role of calcitonin gene-related peptide (CGRP), one of the most important molecules in migraine pathophysiology, in CADASIL patients with migraine-like manifestations is yet to be determined. To sum up, there remain uncertainties whether headache and migraine aura-like manifestations in CADASIL correspond to \"ordinary\" migraine with or without aura seen in routine clinical practice. Therefore, we are still a number of steps from a firm conclusion about the association between CADASIL and migraine.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"65"},"PeriodicalIF":7.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11963438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764003","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":"Association between proton pump inhibitor use and migraine: a systematic review and meta-analysis.","authors":"Prakasini Satapathy, Mahalaqua Nazli Khatib, Nasir Vadia, Soumya V Menon, Kattela Chennakesavulu, Rajashree Panigrahi, Muhammed Shabil, Mahendra Singh, Sanjit Sah, Doddolla Lingamaiah, Khang Wen Goh, Edward Mawejje, Ganesh Bushi","doi":"10.1186/s10194-025-02000-8","DOIUrl":"https://doi.org/10.1186/s10194-025-02000-8","url":null,"abstract":"<p><strong>Background: </strong>Migraine is a common neurological disorder with potential pharmacological triggers. Proton pump inhibitors (PPIs), commonly prescribed for managing gastroesophageal reflux disease and other acid-related gastrointestinal disorders, have been linked to headaches. However, their association with migraine remains unclear. This systematic review and meta-analysis assessed the association between PPI use and the incidence of migraine.</p><p><strong>Method: </strong>A systematic search of PubMed, Embase, and Web of Science was conducted in accordance with the PRISMA framework and registered with PROSPERO (ID: CRD42025644604) to enhance transparency. The search, conducted up to January 2024, included studies focusing on the association between migraine and PPI use. Data screening and extraction were performed using Nested Knowledge software. Meta-analyses were conducted in R software, with heterogeneity assessed through the I² statistic. Pooled adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Sensitivity analyses were also performed to assess the robustness of the results. Gender and migraine subtype were considered in subgroup analyses. Additionally, the GRADE approach was applied to assess the certainty of the evidence across the pooled outcomes.</p><p><strong>Results: </strong>Five studies involving over 1.5 million participants met the inclusion criteria. The overall pooled adjusted odds ratio (aOR) was 2.508 (95% CI, 0.790-7.969; I² = 91.2%). However, there was a significant association in males (aOR, 3.875; 95% CI, 2.413-6.222; I² = 0%) but not in females (aOR, 2.475; 95% CI, 0.563-10.890; I² = 91.1%). No significant differences were found between migraine types: with aura (aOR, 2.079; 95% CI, 0.945-4.576; I² = 25.4%) and without aura (aOR, 2.524; 95% CI, 0.807-7.896; I² = 96.5%). The GRADE assessment indicated a very low certainty of the evidence.</p><p><strong>Conclusion: </strong>This review found no significant overall association between PPI use and migraine. However, a significant association was observed in males but not in females. Further research is needed to clarify this association and explore the underlying causality mechanisms, and migraine subtypes, particularly why the association appears more pronounced in males.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"63"},"PeriodicalIF":7.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743173","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 Global Campaign against Headache, aged 21: a critical self-appraisal, and plans for phase 2.","authors":"Timothy J Steiner, Raquel Gil-Gouveia, Andreas K Husøy, Rigmor Jensen, Zaza Katsarava, Paolo Martelletti, Lars Jacob Stovner, Derya Uluduz","doi":"10.1186/s10194-025-02003-5","DOIUrl":"https://doi.org/10.1186/s10194-025-02003-5","url":null,"abstract":"","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"59"},"PeriodicalIF":7.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743227","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":"Transcutaneous occipital nerve stimulation alleviated migraine related pain by regulating synaptic plasticity and CGRP expression in the periaqueductal gray of male rats.","authors":"Yinglu Liu, Shengli Guo, Yang Li, Jingrui Mao, Xiaoxue Lin, Ruozhuo Liu, Dengfa Zhao, Zhao Dong, Shengyuan Yu, Xun Han","doi":"10.1186/s10194-025-02006-2","DOIUrl":"https://doi.org/10.1186/s10194-025-02006-2","url":null,"abstract":"<p><strong>Background: </strong>Clinical observations have shown that transcutaneous occipital nerve stimulation (tONS) is effective in treating migraine. However, the underlying mechanisms are poorly understood. This study employs a rodent model to investigate the therapeutic effects of tONS on migraine-related pain and to explore potential mechanisms.</p><p><strong>Methods: </strong>The SD rats were used to establish the migraine model by repeated epidural infusions of inflammatory soup (IS). Modified bilateral electrodes were attached noninvasively for tONS treatments. Periorbital mechanical thresholds were assessed using von-Frey filaments, and other pain-related nociceptive behaviors were analyzed through video recordings. The expressions of c-Fos, synaptophysin (Syp) and calcitonin gene-related peptide (CGRP) in the trigeminal nucleus caudalis (TNC) and/or periaqueductal gray (PAG) area were measured by immunofluorescence and western blotting analyses. The excitatory synaptic transmission in the PAG was detected by whole-cell patch-clamp recording among migraine rats.</p><p><strong>Results: </strong>The reduction in periorbital mechanical thresholds induced by repeated IS infusions was partially reversed by tONS treatments in migraine rats. Other pain-related behaviors, including exploration, rest, and unilateral grooming, consistently improved following tONS treatment. The TNC and PAG area were activated after IS modeling, and the CGRP expressions in the PAG significantly decreased after tONS treatments. tONS could inhibit the enhanced excitatory synaptic transmission in the PAG of migraine rats.</p><p><strong>Conclusions: </strong>Our findings suggest that tONS has therapeutic potential in treating migraine, with the PAG excitability and CGRP expression playing a role in its mechanisms of action. tONS may represent a promising non-invasive neuromodulation approach for the management of migraine in the future.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"61"},"PeriodicalIF":7.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743228","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}