Journal of Headache and Pain最新文献

{"title":"Sex differences in expression of CGRP family of receptors and ligands in the rat trigeminal system.","authors":"Aida Maddahi, Jacob C A Edvinsson, Lars Edvinsson","doi":"10.1186/s10194-024-01893-1","DOIUrl":"10.1186/s10194-024-01893-1","url":null,"abstract":"<p><strong>Background: </strong>Calcitonin gene-related peptide (CGRP) is part of the calcitonin peptide family, which includes calcitonin (CT), amylin (AMY), and adrenomedullin (ADM). CGRP and its receptor are highly present in the trigeminovascular system (TVS). Recent research suggests that other members of the calcitonin family could be feasible therapeutic targets in the treatment of migraine. The present study aims to elucidate the distribution of ADM, AMY, CT, and their receptors in the rat TVS, and to explore potential sex differences in their expression.</p><p><strong>Methods: </strong>Trigeminal ganglia (TG) were dissected from male and female adult rats. Protein and gene expression were assessed through immunohistochemistry and RT-qPCR. Additionally, the dura mater was isolated for further investigation of protein expression and fiber localization using immunohistochemistry.</p><p><strong>Results: </strong>Quantitative gene expression analysis revealed the presence of all genes in male and female TGs, except for calcitonin receptor (CTR). Notably, CGRP mRNA levels in TG were several folds higher than those of other genes. The receptor activity-modifying protein-1 (RAMP1) mRNA levels were significantly higher in female compared to male. No AMY or CT immunoreactivity was observed in the TVS. In contrast, immunoreactivity for ADM, CGRP, RAMP1, CTR, and calcitonin-like receptor (CLR) were observed in the cytoplasm of TG neurons. Immunoreactive Aδ-fibers storing RAMP1, ADM and CLR were also identified. RAMP2 and RAMP3 were expressed in nucleus of TG neurons and in satellite glial cells. Furthermore, RAMP1 and CLR were co-localized with CASPR in the nodes of Ranvier located in Aδ-fibers.</p><p><strong>Conclusions: </strong>This study provides valuable insights into the distribution of the CGRP family of peptides and their receptors in the TVS. CGRP mRNA levels in the TG were markedly higher than those of other genes, demonstrating the key role of CGRP. The co-localization of CLR and RAMP1 on Aδ-fibers with CASPR suggests a potential role for this receptor in modulating trigeminal nerve function and neuronal excitability, with implications for migraine pathophysiology. Additionally, RAMP1 mRNA levels were significantly higher in female TG compared to males, indicating sex-specific differences in gene expression. These findings underscore the need for further research into the functional significance of gender-related variations.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"25 1","pages":"193"},"PeriodicalIF":7.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621946","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 lasmiditan, rimegepant and ubrogepant for acute treatment of migraine in triptan insufficient responders: systematic review and network meta-analysis.","authors":"Wattakorn Laohapiboolrattana, Priabprat Jansem, Prakit Anukoolwittaya, Duangnapa Roongpiboonsopit, Akarin Hiransuthikul, Thanakit Pongpitakmetha, Sekh Thanprasertsuk, Wanakorn Rattanawong","doi":"10.1186/s10194-024-01904-1","DOIUrl":"10.1186/s10194-024-01904-1","url":null,"abstract":"<p><strong>Background: </strong>Novel abortive treatments for migraine, ditans and gepants, have promising implications in triptan-insufficient responders with minimal existing comparative data. Our study aims to synthesize evidence through a systematic review and network meta-analysis to assess the comparative efficacy of lasmiditan, rimegepant and ubrogepant in triptan-insufficient responders.</p><p><strong>Method: </strong>We searched PubMed, Embase, CENTRAL, and EBSCO Open Dissertations up to May 2024. We included randomized controlled trials (RCTs) that compared novel abortive treatments, including lasmiditan, rimegepant, and ubrogepant, in migraine patients who self-reported insufficient response to triptans. Outcomes are represented using relative risks with corresponding 95% confidence intervals (CI). The surface under the cumulative ranking curve (SUCRA) was used to rank each medication.</p><p><strong>Results: </strong>A total of five phase 3 RCTs involving 3,004 patients were included in the analysis. All three agents were significantly superior to placebo for two-hour pain freedom (RR = 1.93, 95% CI [1.52, 2.46]), freedom from the most bothersome symptoms at two hours (RR = 1.55, 95% CI [1.37, 1.75]), and pain relief at two hours (RR = 1.46, 95% CI [1.35, 1.58]). No statistically significant differences in efficacy outcomes were observed among the three agents. However, lasmiditan 200 mg had the highest cumulative probability for two-hour pain freedom and relief (SUCRA 0.9, 0.8, respective), while rimegepant led in relieving the most bothersome symptoms (SUCRA 0.7).</p><p><strong>Conclusion: </strong>Lasmiditan, rimegepant, and ubrogepant are effective for acute treatment of migraine in triptan-insufficient responders, with high-dose lasmiditan showing the highest efficacy for pain control.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"25 1","pages":"194"},"PeriodicalIF":7.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11544997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621898","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":"Microbiota alterations are related to migraine food triggers and inflammatory markers in chronic migraine patients with medication overuse headache.","authors":"Doga Vuralli, Merve Ceren Akgor, Hale Gok Dagidir, Pınar Onat, Meltem Yalinay, Ugur Sezerman, Hayrunnisa Bolay","doi":"10.1186/s10194-024-01891-3","DOIUrl":"10.1186/s10194-024-01891-3","url":null,"abstract":"<p><strong>Objective: </strong>Chronic migraine (CM) patients with medication overuse headache (MOH) were recently shown to be associated with leaky gut and inflammation. We aimed to investigate gut microbiota profiles of CM patients with MOH, and their correlations with inflammatory serum parameters, migraine food triggers, and comorbid anxiety and depression.</p><p><strong>Materials and methods: </strong>The study included women participants (32 CM patients with NSAID overuse headache, and 16 healthy non-headache sufferers). Migraine duration, monthly migraine headache days, presence of irritable bowel syndrome symptoms, and HADS-D and HADS-A scores were recorded. Serum samples were collected to measure circulating LPS, HMGB1, HIF-1α, and IL-6. The gut microbiota profiles of the patients were evaluated using fecal samples.</p><p><strong>Results: </strong>Serum LPS, HMGB1, HIF-1α, and IL-6 levels were significantly higher in the CM + MOH group compared to the healthy controls. HADS-A and HADS-D scores were considerably higher in the CM + MOH group compared to the healthy controls. In the microbiota analysis, alpha and beta diversities were similar between the two groups. The class Clostridia, the order Eubacteriales, and the genus Ruminococcus were less abundant in the CM + NSAID overuse headache group compared to the control group. At the genus level Desulfovibrio, Gemmiger, and Dialister and at the species level, Clostridium fessum, Blautia luti, Dorea longicatena, Eubacterium coprostanoligenes, and Gemmiger formicilis were more abundant in the CM + NSAID overuse headache group compared to the control group. Desulfovibrio, Gemmiger, Dialister, Ethanoligenens harbinense, Eubacterium coprostanoligenes, Dorea longicatena, and Thermoclostridium stercorarium showed positive correlations and Clostridia bacteria showed negative correlations with migraine food triggers. Positive correlations were found between LPS and Hapalosiphonaceae, HMGB1 and Melghirimyces, HIF1-α and Rouxeilla and Blautia luti, IL-6 and Melghirimyces and Ruminococcus.</p><p><strong>Conclusion: </strong>In CM patients with MOH, we have revealed the presence of dysbiosis towards an inflammatory state, and positive correlations were shown between altered gut microbiota and inflammatory serum parameters and migraine food triggers.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"25 1","pages":"192"},"PeriodicalIF":7.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11546420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621943","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":"Reduction of neck pain severity in patients with medication-overuse headache.","authors":"Yooha Hong, Hong-Kyun Park, Mi-Kyoung Kang, Sun-Young Oh, Jin-Ju Kang, Heui-Soo Moon, Tae-Jin Song, Mi Ji Lee, Min Kyung Chu, Soo-Jin Cho","doi":"10.1186/s10194-024-01876-2","DOIUrl":"10.1186/s10194-024-01876-2","url":null,"abstract":"<p><strong>Background: </strong>Neck pain and primary headache disorders are highly prevalent in populations and clinical cohorts. Medication-overuse headache (MOH) is a treatable secondary headache, mainly developing in migraine sufferers, that accounts for the majority of patients presenting to headache clinics. Nevertheless, the association between neck pain and MOH has not been reported. This study evaluated the prevalence and clinical course of neck pain in patients with MOH before and after MOH treatment.</p><p><strong>Methods: </strong>We analyzed 635 MOH patients enrolled in a nationwide, prospective, multicenter MOH registry. Demographics and clinical data were collected at baseline and 3 months to evaluate changes in the status and severity of neck pain and headache. Severity of neck pain was graded into 4 groups, and severe neck pain was defined as grade 3 or 4.</p><p><strong>Results: </strong>Among 635 patients with MOH, 366 (57.6%) reported neck pain at baseline. MOH patients with neck pain had an earlier onset of their primary headache disorder (23.4 ± 12.7 vs. 26.2 ± 13.3 years, p = 0.007). Although monthly headache days were comparable between the patients with neck pain and those without neck pain, the neck pain group had higher levels of anxiety (7.4 ± 5.8 vs. 6.4 ± 5.4, p = 0.017), more severe cutaneous allodynia (2.4 ± 3.3 vs. 1.8 ± 3.0, p = 0.038), and poorer quality of life (171.7 ± 70.4 vs. 184.0 ± 68.9, p = 0.029). At 3 months, 456 (71.8%) were followed-up, and 257 (56.4%) were recovered from MOH. Compared to the baseline, the proportion of severe neck pain (40.4% vs. 19.4%, p < 0.001) was decreased. The proportion of severe neck pain was much lower in patients with recovery from MOH compared to those without (4.7% vs. 15.1%, p < 0.001).</p><p><strong>Conclusions: </strong>Neck pain in MOH patients was associated with earlier onset of headache, higher levels of anxiety and allodynia, and poorer quality of life. Improvement in neck pain improvement was linked to recovery from MOH. These findings suggest the potential importance of integrating and management of neck pain into clinical practice for MOH.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"25 1","pages":"190"},"PeriodicalIF":7.3,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11533337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576317","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":"Morphological similarity and white matter structural mapping of new daily persistent headache: a structural connectivity and tract-specific study.","authors":"Di Zhang, Fangrong Zong, Yanliang Mei, Kun Zhao, Dong Qiu, Zhonghua Xiong, Xiaoshuang Li, Hefei Tang, Peng Zhang, Mantian Zhang, Yaqing Zhang, Xueying Yu, Zhe Wang, Yong Liu, Binbin Sui, Yonggang Wang","doi":"10.1186/s10194-024-01899-9","DOIUrl":"10.1186/s10194-024-01899-9","url":null,"abstract":"<p><strong>Background: </strong>New daily persistent headache (NDPH) is a rare primary headache disorder characterized by daily and persistent sudden onset headaches. Specific abnormalities in gray matter and white matter structure are associated with pain, but have not been well studied in NDPH. The objective of this work is to explore the fiber tracts and structural connectivity, which can help reveal unique gray and white matter structural abnormalities in NDPH.</p><p><strong>Methods: </strong>The regional radiomics similarity networks were calculated from T1 weighted (T1w) MRI to depict the gray matter structure. The fiber connectivity matrices weighted by diffusion metrics like fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD) were built, meanwhile the fiber tracts were segmented by anatomically-guided superficial fiber segmentation (Anat-SFSeg) method to explore the white matter structure from diffusion MRI. The considerable different neuroimaging features between NDPH and healthy controls (HC) were extracted from the connectivity and tract-based analyses. Finally, decision tree regression was used to predict the clinical scores (i.e. pain intensity) from the above neuroimaging features.</p><p><strong>Results: </strong>T1w and diffusion MRI data were available in 51 participants after quality control: 22 patients with NDPH and 29 HCs. Significantly decreased morphological similarity was found between the right superior frontal gyrus and right hippocampus. The superficial white matter (SWM) showed significantly decreased FA in fiber tracts including the right superficial-frontal, left superficial-occipital, bilateral superficial-occipital-temporal (Sup-OT) and right superficial-temporal, meanwhile significant increased RD was found in the left Sup-OT. For the fiber connectivity, NDPH showed significantly decreased FA in the bilateral basal ganglion and temporal lobe, increased MD in the right frontal lobe, and increased RD in the right frontal lobe and left temporal-occipital lobe. Clinical scores could be predicted dominantly by the above significantly different neuroimaging features through decision tree regression.</p><p><strong>Conclusions: </strong>Our research indicates the structural abnormalities of SWM and the neural pathways projected between regions like right hippocampus and left caudate nucleus, along with morphological similarity changes between the right superior frontal gyrus and right hippocampus, constitute the pathological features of NDPH. The decision tree regression demonstrates correlations between these structural changes and clinical scores.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"25 1","pages":"191"},"PeriodicalIF":7.3,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11533401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576314","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":"Hallmarks of primary headache: part 1 - migraine.","authors":"Alberto Raggi, Matilde Leonardi, Marco Arruda, Valeria Caponnetto, Matteo Castaldo, Gianluca Coppola, Adriana Della Pietra, Xiangning Fan, David Garcia-Azorin, Parisa Gazerani, Lou Grangeon, Licia Grazzi, Fu-Jung Hsiao, Keiko Ihara, Alejandro Labastida-Ramirez, Kristin Sophie Lange, Marco Lisicki, Alessia Marcassoli, Danilo Antonio Montisano, Dilara Onan, Agnese Onofri, Lanfranco Pellesi, Mario Peres, Igor Petrušić, Bianca Raffaelli, Eloisa Rubio-Beltran, Andreas Straube, Sebastian Straube, Tsubasa Takizawa, Claudio Tana, Michela Tinelli, Massimiliano Valeriani, Simone Vigneri, Doga Vuralli, Marta Waliszewska-Prosół, Wei Wang, Yonggang Wang, William Wells-Gatnik, Tissa Wijeratne, Paolo Martelletti","doi":"10.1186/s10194-024-01889-x","DOIUrl":"10.1186/s10194-024-01889-x","url":null,"abstract":"<p><strong>Background and aim: </strong>Migraine is a common disabling conditions which, globally, affects 15.2% of the population. It is the second cause of health loss in terms of years lived with disability, the first among women. Despite being so common, it is poorly recognised and too often undertreated. Specialty centres and neurologists with specific expertise on headache disorders have the knowledge to provide specific care: however, those who do not regularly treat patients with migraine will benefit from a synopsis on the most relevant and updated information about this condition. This paper presents a comprehensive view on the hallmarks of migraine, from genetics and diagnostic markers, up to treatments and societal impact, and reports the elements that identify migraine specific features.</p><p><strong>Main results: </strong>The most relevant hallmark of migraine is that it has common and individual features together. Besides the known clinical manifestations, migraine presentation is heterogeneous with regard to frequency of attacks, presence of aura, response to therapy, associated comorbidities or other symptoms, which likely reflect migraine heterogeneous genetic and molecular basis. The amount of therapies for acute and for prophylactic treatment is really wide, and one of the difficulties is with finding the best treatment for the single patient. In addition to this, patients carry out different daily life activities, and might show lifestyle habits which are not entirely adequate to manage migraine day by day. Education will be more and more important as a strategy of brain health promotion, because this will enable reducing the amount of subjects needing specialty care, thus leaving it to those who require it in reason of refractory condition or presence of comorbidities.</p><p><strong>Conclusions: </strong>Recognizing the hallmarks of migraine and the features of single patients enables prescribing specific pharmacological and non-pharmacological treatments. Medical research on headaches today particularly suffers from the syndrome of single-disease approach, but it is important to have a cross-sectional and joint vision with other close specialties, in order to treat our patients with a comprehensive approach that a heterogeneous condition like migraine requires.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"25 1","pages":"189"},"PeriodicalIF":7.3,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558051","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":"Regional distribution of unbound eletriptan and sumatriptan in the CNS and PNS in rats: implications for a potential central action.","authors":"Nana Svane, Frida Bällgren, Aghavni Ginosyan, Mie Kristensen, Birger Brodin, Irena Loryan","doi":"10.1186/s10194-024-01894-0","DOIUrl":"10.1186/s10194-024-01894-0","url":null,"abstract":"<p><strong>Background: </strong>Triptans are potent 5-HT_1B/1D/1F receptor agonists used in migraine therapy, thought to act through peripheral mechanisms. It remains unclear whether triptans cross the blood-brain barrier (BBB) sufficiently to stimulate central 5-HT_1B/1D/1F receptors. This study investigates the disposition of eletriptan and sumatriptan in central nervous system (CNS) and peripheral nervous system (PNS) regions and predicts regional 5-HT_1B/1D/1F receptor occupancies at clinically relevant concentrations.</p><p><strong>Methods: </strong>Using the Combinatory Mapping Approach (CMA) for regions of interest (ROI), we assessed the unbound tissue-to-plasma concentration ratio (K_{p, uu, ROI}) in rats at steady state across CNS (hypothalamus, brain stem, cerebellum, frontal cortex, parietal cortex, striatum, hippocampus, whole brain, and spinal cord) and PNS (trigeminal ganglion and sciatic nerve) regions. We used K_{p, uu, ROI} values to estimate unbound target-site concentrations and 5-HT_1B/1D/1F receptor occupancies in humans.</p><p><strong>Results: </strong>We observed heterogenous triptan transport across CNS and PNS regions with the highest extent of unbound drug transport across the blood-nerve barrier in the trigeminal ganglion (K_{p, uu, TG}: eletriptan: 0.519, and sumatriptan: 0.923). Both drugs displayed restricted entry across the BBB (K_{p, uu, whole brain}: eletriptan: 0.058, and sumatriptan: 0.045) combined with high inter-regional variability. We estimated near-complete receptor occupancy in the trigeminal ganglion, while lower occupancies were observed in the whole brain, irrespective of the drug or receptor subtype. For instance, eletriptan was predicted to achieve 84% 5-HT_1B receptor occupancy in the trigeminal ganglion and 37% in the whole brain at clinically relevant concentrations.</p><p><strong>Conclusions: </strong>This study suggests that despite low BBB transport, both eletriptan and sumatriptan achieve unbound concentrations sufficient to stimulate 5-HT_1B, 5-HT_1D, and 5-HT_1F receptors not only in the trigeminal ganglion, but also in the CNS. Further research is needed to determine whether central mechanisms contribute to triptan's antimigraine effect and/or side effects.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"25 1","pages":"187"},"PeriodicalIF":7.3,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545870","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: PACAP-38 and sex hormones in women with migraine: exploratory analysis of a cross-sectional, matched cohort study.","authors":"Elisabeth Storch, Lucas H Overeem, Maria Terhart, Mira P Fitzek, Kristin S Lange, Uwe Reuter, Bianca Raffaelli","doi":"10.1186/s10194-024-01898-w","DOIUrl":"10.1186/s10194-024-01898-w","url":null,"abstract":"","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"25 1","pages":"188"},"PeriodicalIF":7.3,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered brainstem-cortex activation and interaction in migraine patients: somatosensory evoked EEG responses with machine learning.","authors":"Fu-Jung Hsiao, Wei-Ta Chen, Hung-Yu Liu, Yu-Te Wu, Yen-Feng Wang, Li-Ling Hope Pan, Kuan-Lin Lai, Shih-Pin Chen, Gianluca Coppola, Shuu-Jiun Wang","doi":"10.1186/s10194-024-01892-2","DOIUrl":"10.1186/s10194-024-01892-2","url":null,"abstract":"<p><strong>Background: </strong>To gain a comprehensive understanding of the altered sensory processing in patients with migraine, in this study, we developed an electroencephalography (EEG) protocol for examining brainstem and cortical responses to sensory stimulation. Furthermore, machine learning techniques were employed to identify neural signatures from evoked brainstem-cortex activation and their interactions, facilitating the identification of the presence and subtype of migraine.</p><p><strong>Methods: </strong>This study analysed 1,000-epoch-averaged somatosensory evoked responses from 342 participants, comprising 113 healthy controls (HCs), 106 patients with chronic migraine (CM), and 123 patients with episodic migraine (EM). Activation amplitude and effective connectivity were obtained using weighted minimum norm estimates with spectral Granger causality analysis. This study used support vector machine algorithms to develop classification models; multimodal data (amplitude, connectivity, and scores of psychometric assessments) were applied to assess the reliability and generalisability of the identification results from the classification models.</p><p><strong>Results: </strong>The findings revealed that patients with migraine exhibited reduced amplitudes for responses in both the brainstem and cortical regions and increased effective connectivity between these regions in the gamma and high-gamma frequency bands. The classification model with characteristic features performed well in distinguishing patients with CM from HCs, achieving an accuracy of 81.8% and an area under the curve (AUC) of 0.86 during training and an accuracy of 76.2% and an AUC of 0.89 during independent testing. Similarly, the model effectively identified patients with EM, with an accuracy of 77.5% and an AUC of 0.84 during training and an accuracy of 87% and an AUC of 0.88 during independent testing. Additionally, the model successfully differentiated patients with CM from patients with EM, with an accuracy of 70.5% and an AUC of 0.73 during training and an accuracy of 72.7% and an AUC of 0.74 during independent testing.</p><p><strong>Conclusion: </strong>Altered brainstem-cortex activation and interaction are characteristic of the abnormal sensory processing in migraine. Combining evoked activity analysis with machine learning offers a reliable and generalisable tool for identifying patients with migraine and for assessing the severity of their condition. Thus, this approach is an effective and rapid diagnostic tool for clinicians.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"25 1","pages":"185"},"PeriodicalIF":7.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11514809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522072","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":"Causal relationships between cortical brain structural alterations and migraine subtypes: a bidirectional Mendelian randomization study of 2,347 neuroimaging phenotypes.","authors":"Zuhao Sun, Mengge Liu, Guoshu Zhao, Zhihui Zhang, Jinglei Xu, Linlin Song, Wanwan Zhang, Shaoying Wang, Linlin Jia, Qian Wu, Yue Wu, Haolin Wang, Nannan Liu, Qian Su, Feng Liu","doi":"10.1186/s10194-024-01896-y","DOIUrl":"10.1186/s10194-024-01896-y","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have shown that migraines are associated with brain structural changes. However, the causal relationships between these changes and migraine, as well as its subtypes, migraine with aura (MA) and migraine without aura (MO), remain largely unclear.</p><p><strong>Methods: </strong>We utilized genome-wide association study (GWAS) summary statistics from European cohorts for 2,347 cortical structural magnetic resonance imaging (MRI) phenotypes, derived from both T1-weighted and diffusion tensor imaging scans (n = 36,663), with migraine and its subtypes (n = 147,970-375,752). Cortical phenotypes included both macrostructural (e.g., cortical thickness, surface area) and microstructural (e.g., fractional anisotropy, mean diffusivity) features. Genetic correlations were first assessed to identify significant associations, followed by bidirectional Mendelian randomization (MR) analyses to determine causal relationships between these brain phenotypes and migraine, as well as its subtypes (MA and MO). Sensitivity analyses were applied to ensure the robustness of the results.</p><p><strong>Results: </strong>Genetic correlation analysis identified 510 significant associations between cortical structural phenotypes and migraine across 401 distinct traits. Forward MR analysis revealed nine significant causal effects of cortical structural changes on migraine risk. Specifically, increased cortical thickness and local gyrification index in specific cortical regions were associated with a decreased risk of overall migraine, MA, and MO, while intracellular volume fraction and orientation diffusion index in specific regions increased the risk of MA and MO. Reverse MR analysis demonstrated that MA causally increased mean diffusivity in the insular and frontal opercular cortex. Sensitivity analyses confirmed the robustness of these findings, with no evidence of horizontal pleiotropy or heterogeneity.</p><p><strong>Conclusion: </strong>This study identifies causal relationships between cortical neuroimaging phenotypes and migraine, highlighting potential biomarkers for migraine diagnosis, treatment, and prevention.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"25 1","pages":"186"},"PeriodicalIF":7.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11514853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522073","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}