Jacob C A Edvinsson, Caroline Ran, Felicia Jennysdotter Olofsgård, Anna Steinberg, Lars Edvinsson, Andrea Carmine Belin
{"title":"MERTK in the rat trigeminal system: a potential novel target for cluster headache?","authors":"Jacob C A Edvinsson, Caroline Ran, Felicia Jennysdotter Olofsgård, Anna Steinberg, Lars Edvinsson, Andrea Carmine Belin","doi":"10.1186/s10194-024-01791-6","DOIUrl":"10.1186/s10194-024-01791-6","url":null,"abstract":"<p><p>The trigeminal system is key to the pathophysiology of migraine and cluster headache, two primary headache disorders that share many features. Recently, MER proto-oncogene tyrosine kinase (MERTK), a cell surface receptor, was strongly associated with cluster headache through genetic studies. Further, the MERTK ligand galectin-3 has been found to be elevated in serum of migraine patients. In this study, MERTK and MERTK ligands were investigated in key tissue to better understand their potential implication in the pathophysiology of primary headache disorders. Immunohistochemistry was used to map MERTK and galectin-3 expression in rat trigeminal ganglia. RT-qPCR was used to assess MERTK gene expression in blood, and ELISA immunoassays were used for MERTK ligand quantification in serum from study participants with and without cluster headache. MERTK gene expression was elevated in blood samples from study participants with cluster headache compared to controls. In addition, MERTK ligand galectin-3 was found at increased concentration in the serum of study participants with cluster headache, whereas the levels of MERTK ligands growth arrest specific 6 and protein S unaffected. MERTK and galectin-3 were both expressed in rat trigeminal ganglia. Galectin-3 was primarily localized in smaller neurons and to a lesser extent in C-fibres, while MERTK was found in satellite glia cells and in the outer membrane of Schwann cells. Interestingly, a strong MERTK signal was found specifically in the region proximal to the nodes of Ranvier. The overexpression of MERTK and galectin-3 in tissue from study participants with cluster headache, as well as the presence of MERTK in rat peripheral satellite glia cells and Schwann cells in the trigeminal ganglia, further highlights MERTK signalling as an interesting potential future therapeutic target in primary headache.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11119394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141088069","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":"Aberrant cerebral blood flow and functional connectivity in patients with vestibular migraine: a resting-state ASL and fMRI study.","authors":"Zhengwei Chen, Yueji Liu, Cunxin Lin, Zhining Li, Junjun Shan, Zuowei Duan, Liangqun Rong, Xiue Wei, Lijie Xiao, Haiyan Liu","doi":"10.1186/s10194-024-01792-5","DOIUrl":"10.1186/s10194-024-01792-5","url":null,"abstract":"<p><strong>Background: </strong>Prior neuroimaging studies on vestibular migraine (VM) have extensively certified the functional and structural alterations in multiple brain regions and networks. However, few studies have assessed the cerebral blood flow (CBF) in VM patients using arterial spin labeling (ASL). The present study aimed to investigate CBF and functional connectivity (FC) alterations in VM patients during interictal periods.</p><p><strong>Methods: </strong>We evaluated 52 VM patients and 46 healthy controls (HC) who received resting-state pseudo-continuous ASL and functional magnetic resonance imaging (fMRI) scanning. Comparisons of voxel-based CBF and seed-based FC were performed between the two groups. Brain regions showed significant group differences in CBF analyses were chosen as seeds in FC analyses. Additionally, the associations between abnormal imaging results and clinical features were explored.</p><p><strong>Results: </strong>Compared with HC, VM patients showed higher normalized CBF in the right precentral gyrus (PreCG), left postcentral gyrus (PostCG), left superior frontal gyrus and bilateral insular (p < 0.05, FDR corrected). Furthermore, VM patients exhibited increased FC between the right PreCG and areas of the left PostCG, left cuneus and right lingual gyrus (p < 0.05, FDR corrected). In addition, we observed decreased FC between the left insular and regions of the left thalamus and right anterior cingulate cortex, as well as increased FC between the left insular and right fusiform gyrus in VM patients (p < 0.05, FDR corrected). Moreover, these variations in brain perfusion and FC were significantly correlated with multiple clinical features including frequency of migraine symptoms, frequency of vestibular symptoms and disease duration of VM (all p < 0.05).</p><p><strong>Conclusions: </strong>Patients with VM during interictal period showed hyperperfusion and abnormal resting-state FC in brain regions potentially contributed to disrupted multi-sensory and autonomic processing, as well as impaired ocular motor control, pain modulation and emotional regulation. Our study provided novel insights into the complex neuropathology of VM from a CBF perspective.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11107056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141075778","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}
Richard B Lipton, Stephanie J Nahas, Patricia Pozo-Rosich, Tanya Bilchik, Peter McAllister, Michelle Finnegan, Yingyi Liu, Natty Chalermpalanupap, Brett Dabruzzo, David W Dodick
{"title":"Sustained response to atogepant in episodic migraine: post hoc analyses of a 12-week randomized trial and a 52-week long-term safety trial.","authors":"Richard B Lipton, Stephanie J Nahas, Patricia Pozo-Rosich, Tanya Bilchik, Peter McAllister, Michelle Finnegan, Yingyi Liu, Natty Chalermpalanupap, Brett Dabruzzo, David W Dodick","doi":"10.1186/s10194-024-01783-6","DOIUrl":"10.1186/s10194-024-01783-6","url":null,"abstract":"<p><strong>Background: </strong>Atogepant is an oral calcitonin gene-related peptide receptor antagonist approved for the preventive treatment of migraine in adults. These analyses evaluated the proportions of clinical trial participants who experienced sustained responses to atogepant over 12 or 52 weeks of treatment.</p><p><strong>Methods: </strong>These were post hoc analyses of ADVANCE, a 12-week, double-blind, randomized trial of atogepant 10, 30, and 60 mg once daily vs. placebo for the preventive treatment of episodic migraine, and a separate open-label long-term safety (LTS) trial of atogepant 60 mg once daily over 52 weeks. The 60 mg dose of atogepant was used to detect safety issues. An initial response was defined as ≥50%, ≥75%, or 100% reduction from baseline in MMDs in month 1 for ADVANCE or quarter 1 for the LTS trial. The proportions of participants who continued to experience a response above each response-defining threshold through each subsequent month (for ADVANCE) or each quarter (for LTS) were calculated.</p><p><strong>Results: </strong>In ADVANCE, sustained response rates during months 2 and 3 varied with dose and were as follows: 70.8-81.1% following an initial ≥50% response, 47.3-61.9% following an initial ≥75% response, and 34.8-41.7% following an initial 100% response. Of those who experienced an initial ≥75% or 100% response during month 1, more than 79% continued to experience at least a 50% response during both months 2 and 3. During the LTS trial, sustained response rates through quarters 2, 3, and 4 were 84.7% following an initial ≥50% response, 72.6% following an initial ≥75% response, and 37.8% following an initial 100% response. Of those who experienced an initial ≥75% or 100% response during quarter 1, more than 90% continued to experience at least a 50% response through quarters 2, 3, and 4.</p><p><strong>Conclusion: </strong>Over 70% of participants who experienced an initial response with atogepant treatment had a sustained response with continued treatment.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov: NCT03777059 (submitted: December 13, 2018); NCT03700320 (submitted: September 25, 2018).</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11107063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141075779","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":"Poor healthy lifestyle and life's essential 8 are associated with higher risk of new-onset migraine: a prospective cohort study.","authors":"Yuexiu Lei, Lili Zhang, Zhengming Shan, Quan Gan, Qingfang Xie, Ying Huang, Wen Yan, Zheman Xiao","doi":"10.1186/s10194-024-01785-4","DOIUrl":"10.1186/s10194-024-01785-4","url":null,"abstract":"<p><strong>Background: </strong>Lifestyle are closely related to migraine. However, there is a lack of studies investigating the association between Healthy lifestyle or Life's Essential 8 (LE8) and the risk of migraine. The objective of this research was to investigate the relationship between Healthy lifestyle scores and Life's essential 8 scores, and migraine.</p><p><strong>Methods: </strong>332,895 UK Biobank participants without migraine were included. Healthy lifestyle were assessed using seven lifestyle factors, and categorized as poor, intermediate, or ideal. LE8, based on the American Heart Association (AHA) Guidelines for Cardiovascular Health (CVH), consist of eight indicators classified as low, moderate, or high CVH. The Cox proportional hazard model was employed to examine the association between Healthy lifestyle scores, LE8 scores, and migraine, with calculations for population-attributable fraction (PAF) and cumulative incidence.</p><p><strong>Results: </strong>During a median follow-up of 13.58 years, participants in intermediate (HR: 0.91; 95% CI: 0.85, 0.99) or ideal category of Healthy lifestyle (HR: 0.81; 95% CI: 0.73, 0.91) significantly reduced migraine risk compared to the poor category. Similarly, high CVH (HR: 0.73; 95% CI: 0.58, 0.92) also lowered migraine risk, while moderate CVH (HR: 0.93; 95% CI: 0.85, 1.02) did not show a difference compared to low CVH. If all individuals adhered to higher categories of Healthy lifestyle and LE8, approximately 11.38% and 22.05% of migraine cases could be prevented. Among individual lifestyle factors, maintaining an ideal body mass index (BMI), physical activity, sleep duration, sleep pattern, and sedentary time were associated with substantial reductions in migraine risk, by 5.65%, 0.81%, 10.16%, 16.39%, and 6.57%, respectively.</p><p><strong>Conclusion: </strong>Our study provides evidence that poor Healthy lifestyle and Life's Essential 8 are associated with higher risk of new-onset migraine.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11100122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957267","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}
Yang Li, Chenhao Li, Qi-Yu Chen, Shun Hao, Jingrui Mao, Wenwen Zhang, Xun Han, Zhao Dong, Ruozhuo Liu, Wenjing Tang, Min Zhuo, Shengyuan Yu, Yinglu Liu
{"title":"Alleviation of migraine related pain and anxiety by inhibiting calcium-stimulating AC1-dependent CGRP in the insula of adult rats.","authors":"Yang Li, Chenhao Li, Qi-Yu Chen, Shun Hao, Jingrui Mao, Wenwen Zhang, Xun Han, Zhao Dong, Ruozhuo Liu, Wenjing Tang, Min Zhuo, Shengyuan Yu, Yinglu Liu","doi":"10.1186/s10194-024-01778-3","DOIUrl":"10.1186/s10194-024-01778-3","url":null,"abstract":"<p><strong>Background: </strong>Recent animal and clinical findings consistently highlight the critical role of calcitonin gene-related peptide (CGRP) in chronic migraine (CM) and related emotional responses. CGRP antibodies and receptor antagonists have been approved for CM treatment. However, the underlying CGRP-related signaling pathways in the pain-related cortex remain poorly understood.</p><p><strong>Methods: </strong>The SD rats were used to establish the CM model by dural infusions of inflammatory soup. Periorbital mechanical thresholds were assessed using von-Frey filaments, and anxiety-like behaviors were observed via open field and elevated plus maze tests. Expression of c-Fos, CGRP and NMDA GluN2B receptors was detected using immunofluorescence and western blotting analyses. The excitatory synaptic transmission was detected by whole-cell patch-clamp recording. A human-used adenylate cyclase 1 (AC1) inhibitor, hNB001, was applied via insula stereotaxic and intraperitoneal injections in CM rats.</p><p><strong>Results: </strong>The insular cortex (IC) was activated in the migraine model rats. Glutamate-mediated excitatory transmission and NMDA GluN2B receptors in the IC were potentiated. CGRP levels in the IC significantly increased during nociceptive and anxiety-like activities. Locally applied hNB001 in the IC or intraperitoneally alleviated periorbital mechanical thresholds and anxiety behaviors in migraine rats. Furthermore, CGRP expression in the IC decreased after the hNB001 application.</p><p><strong>Conclusions: </strong>Our study indicated that AC1-dependent IC plasticity contributes to migraine and AC1 may be a promising target for treating migraine in the future.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11100092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957262","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}
Armin Scheffler, Pauline Wenzel, Merle Bendig, Astrid Gendolla, Jale Basten, Christoph Kleinschnitz, Michael Nsaka, Diana Lindner, Steffen Naegel, Philipp Burow, Robert Fleischmann, Dagny Holle
{"title":"Effectiveness and tolerability of eptinezumab in treating patients with migraine resistant to conventional preventive medications and CGRP (receptor) antibodies: a multicentre retrospective real-world analysis from Germany.","authors":"Armin Scheffler, Pauline Wenzel, Merle Bendig, Astrid Gendolla, Jale Basten, Christoph Kleinschnitz, Michael Nsaka, Diana Lindner, Steffen Naegel, Philipp Burow, Robert Fleischmann, Dagny Holle","doi":"10.1186/s10194-024-01788-1","DOIUrl":"10.1186/s10194-024-01788-1","url":null,"abstract":"<p><strong>Background: </strong>Eptinezumab is a monoclonal antibody that targets calcitonin gene-related peptide (CGRP mAb) and is used for migraine prophylaxis. Efficacy data are mainly from clinical trials, real-world data are hardly available yet. Reimbursement policy in Germany leads to eptinezumab mainly being used in patients having failed pre-treatment with other CGRP mAb. To date, it is unclear whether eptinezumab is efficacious and well tolerated in this population and how the treatment response differs from patients who are naive to CGRP mAbs.</p><p><strong>Methods: </strong>We analysed clinical routine data of 79 patients (episodic migraine (EM): n = 19; chronic migraine (CM): n = 60) from four different centres in Germany. All patients were treated with eptinezumab (100mg). Differences in monthly headache (MHD), migraine (MMD) and acute medication days (AMD) after three months were analysed. The correlation of response with the number of CGRP mAb failures was evaluated. Significance level has been corrected (alpha = 0.017).</p><p><strong>Results: </strong>After three months MHD, MMD and AMD were significantly reduced. In EM, the median reduction for MHD was 4.0 days (IQR: -6.5 to -1.0; p = 0.001), for MMD 3.0 days (IQR: -5.5 to -1.5; p < 0.001) and for AMD 2.0 days (IQR: -5.0 to -0.5; p = 0.006). In CM, median reduction of MHD was 4 days (IQR: -8.0 to 0.0; p < 0.001), 3.0 days (IQR: -6.0 to-1.0; p < 0.001) for MMD and 1.0 day (IQR: -5.0 to 0.0; p < 0.001) for AMD. All patients were resistant to conventional preventive therapies and most to CGRP mAbs. Fourteen patients had never received a CGRP mAb and 65 patients had received at least one mAb without sufficient effectiveness and/or intolerability (one: n = 20, two: n = 28, three: n = 17). There was a significant association between the number of prior therapies and the 30% MHD responder rate (none: 78.6%, one: 45.0%, two: 32.1%, three: 23.5%, p = 0.010). Regarding tolerability, 10.4% (8/77) reported mild side effects.</p><p><strong>Conclusions: </strong>The effectiveness of eptinezumab is significantly reduced in patients who have not previously responded to other CGRP mAbs. However, limitations such as the retrospective nature of the analysis, the small sample size and the short treatment period with only the lower dose of eptinezumab must be considered when interpreting the results.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11097519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957263","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":"MicroRNA profiling in women with migraine: effects of CGRP-targeting treatment.","authors":"Raffaele Ornello, Veronica Zelli, Chiara Compagnoni, Valeria Caponnetto, Eleonora De Matteis, Cindy Tiseo, Alessandra Tessitore, Simona Sacco","doi":"10.1186/s10194-024-01787-2","DOIUrl":"10.1186/s10194-024-01787-2","url":null,"abstract":"<p><strong>Background: </strong>Migraine lacks biomarkers that can trace the biological pathways of the disease and predict the effectiveness of treatments. Monoclonal antibodies targeting calcitonin gene-related peptide pathway - including erenumab - offer the opportunity of investigating potential migraine biomarkers due to their specific mechanism of action in preventing both episodic (EM) and chronic (CM) migraine. Our study aims at evaluating the expression levels of circulating microRNAs (miRNAs) according to migraine type, before and after treatment with erenumab and based on treatment response, in order to identify miRNAs with potential role as epigenetic biomarkers.</p><p><strong>Methods: </strong>The study included women aged 25-50 years with EM or CM treated with erenumab according to clinical indications. MiRNAs expression levels were assessed before (baseline) and after a 16-week treatment with erenumab, 140 mg every four weeks (post-treatment). An extensive miRNAs profiling was performed by qRT-PCR in small, pooled groups of ≤ 8 women each, classified according to migraine frequency (EM and CM) and the degree of response to erenumab. The expression levels of selected miRNAs were also validated using single miRNA assays in each woman with EM and CM.</p><p><strong>Results: </strong>During the study, 36 women with migraine (19 with EM and 17 with CM) out of 40 who were initially screened, performed the assessment of miRNA expression at baseline and post-treatment, Erenumab treatment significantly improved migraine burden in both EM and CM. MiRNA profiling revealed differential expression levels of a wide set of miRNAs (hsa-let-7d-3p, hsa-miR-106b-3p, hsa-miR-122-5p, hsa-miR-143-3p, hsa-miR-144-3p, hsa-miR-16-5p, hsa-miR-181a-5p, hsa-miR-221-3p, hsa-miR-25-3p, hsa-miR-29b-2-5p, hsa-miR-326, miR-363-3p, hsa-miR-424-5p, hsa-miR-485-3p, hsa-miR-532-5p, hsa-miR-543, hsa-miR-629-5p, hsa-miR-660-5p, hsa-miR-92a-3p) depending on treatment response. Among them, single miRNA assays confirmed the progressive decrease of hsa-miR-143-3p expression levels in relation to increasing response to erenumab in women with EM (7 with low, 6 with medium, and 6 with high response; p = 0.02). Additionally, single assays showed higher hsa-miR-34a-5p and hsa-miR-382-5p expression levels at baseline in women with CM compared with those with EM (p = 0.0002 and p = 0.0007, respectively), as well as their expression level decrease in women with CM from baseline to follow-up (p = 0.04 and p = 0.02, respectively).</p><p><strong>Conclusions: </strong>Our study suggests that targeting the CGRP pathway in migraine changes the expression levels of certain miRNAs. These miRNA levels are linked to the levels of response to CGRP receptor blockage. Future research challenges include assigning specific functions to the modulated miRNAs to unravel pathways modulated by the disease and the treatment.</p><p><strong>Trial registration: </strong>The study was registered in clinical","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11100066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957264","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}
Siew Wan Hee, Shilpa Patel, Harbinder Sandhu, Manjit S Matharu, Martin Underwood
{"title":"Does pain self-efficacy predict, moderate or mediate outcomes in people with chronic headache; an exploratory analysis of the CHESS trial.","authors":"Siew Wan Hee, Shilpa Patel, Harbinder Sandhu, Manjit S Matharu, Martin Underwood","doi":"10.1186/s10194-024-01768-5","DOIUrl":"10.1186/s10194-024-01768-5","url":null,"abstract":"<p><strong>Background: </strong>Chronic headache disorders are disabling. The CHESS trial studied the effects of a short non-pharmacological intervention of education with self-management support for people affected by migraine and/or tension type headache for at least 15 days per month for at least three months. There were no statistically significant effects on the Headache Impact Test-6 (HIT-6) at 12-months. However, we observed improvement in pain self-efficacy questionnaire (PSEQ) and short-term HIT-6. We explored the impact of the CHESS intervention on PSEQ, and subsequently, on the HIT-6 and chronic headache quality of life questionnaire (CH-QLQ) at four, eighth and 12 months.</p><p><strong>Methods: </strong>We included all 736 participants from the CHESS trial. We used simple linear regression models to explore the change of HIT-6 and CH-QLQ with treatment and PSEQ at baseline (predictor analysis), and the interaction between treatment and baseline PSEQ (moderator analysis). We considered the change of PSEQ from baseline to four months as a mediator in the mediation analysis.</p><p><strong>Results: </strong>Baseline PSEQ neither predicted nor moderated outcomes. The prediction effect on change of HIT-6 from baseline to 12 months was 0.01 (95% CI, -0.03 to 0.04) and the interaction (moderation) effect was -0.07 (95% CI, -0.15 to 0.002). However, the change of PSEQ from baseline to 4-month mediated the HIT-6 (baseline to 8-, and 12-month) and all components of CH-QLQ (baseline to 8-, and 12-month). The CHESS intervention improved the mediated variable, PSEQ, by 2.34 (95% CI, 0.484 to 4.187) units and this corresponds to an increase of 0.21 (95% CI, 0.03 to 0.45) units in HIT-6 at 12-months. The largest mediated effect was observed on the CH-QLQ Emotional Function, an increase of 1.12 (95% CI, 0.22 to 2.20).</p><p><strong>Conclusions: </strong>PSEQ was not an effective predictor of outcome. However, change of short-term PSEQ mediated all outcomes, albeit minimally. Future behavioural therapy for chronic headache may need to consider how to achieve larger, and more sustained increases level of self-efficacy than that achieved within the CHESS trial.</p><p><strong>Trial registration: </strong>ISRCTN79708100.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11094916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922334","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}
Sara Helena Schramm, I Tenhagen, M Jokisch, J Gronewold, S Moebus, S Caspers, Z Katsarava, R Erbel, A Stang, B Schmidt
{"title":"Migraine or any headaches and white matter hyperintensities and their progression in women and men.","authors":"Sara Helena Schramm, I Tenhagen, M Jokisch, J Gronewold, S Moebus, S Caspers, Z Katsarava, R Erbel, A Stang, B Schmidt","doi":"10.1186/s10194-024-01782-7","DOIUrl":"10.1186/s10194-024-01782-7","url":null,"abstract":"<p><strong>Background: </strong>Cross-sectional and longitudinal studies have been conducted to investigate the association between migraine and any headache and white matter hyperintensities (WMH). However, studies are inconsistent regarding the strength of the association and its clinical significance. The aim of our study was to investigate the association between headache and its subtypes (migraine with aura (MigA+), migraine without aura (MigA-), non-migraine headache (nonMigHA)) and WMH and its course in the population-based 1000BRAINS study using state-of-the-art imaging techniques and migraine classification according to modified international classification of headache disorders.</p><p><strong>Methods: </strong>Data from 1062 participants (45% women, 60.9 ± 13.0 years) with ever or never headache (neverHA) and complete quantitative (WMH volume) and qualitative (Fazekas classification) WMH data at first imaging and after 3.7 ± 0.7 years (393 participants) were analyzed. The sex-specific association between headache and its subtypes and WMH volume and its change was evaluated by linear regression, between headache and its subtypes and Fazekas score high vs. low (2-3 vs. 0-1) by log-binomial regression, adjusted for confounders.</p><p><strong>Results: </strong>The lifetime prevalence of headache was 77.5% (10.5% MigA+, 26.9% MigA-, 40.1% nonMigHA). The median WMH volume was 4005 (IQR: 2454-6880) mm3 in women and 4812 (2842-8445) mm3 in men. Women with any headaches (all headache types combined) had a 1.23 [1.04; 1.45]-fold higher WMH volume than women who reported never having had a headache. There was no indication of higher Fazekas grading or more WMH progression in women with migraine or any headaches. Men with migraine or any headaches did not have more WMH or WMH progression compared to men without migraine or men who never had headache.</p><p><strong>Conclusions: </strong>Our study demonstrated no increased occurrence or progression of WMH in participants with mgiraine. But, our results provide some evidence of greater WMH volume in women with headache of any type including migraine. The underlying pathomechanisms and the reasons why this was not shown in men are unclear and require further research.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11094904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922336","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}
Jaisan Islam, Md Taufiqur Rahman, Elina Kc, Young Seok Park
{"title":"Deciphering the functional role of insular cortex stratification in trigeminal neuropathic pain.","authors":"Jaisan Islam, Md Taufiqur Rahman, Elina Kc, Young Seok Park","doi":"10.1186/s10194-024-01784-5","DOIUrl":"10.1186/s10194-024-01784-5","url":null,"abstract":"<p><p>Trigeminal neuropathic pain (TNP) is a major concern in both dentistry and medicine. The progression from normal to chronic TNP through activation of the insular cortex (IC) is thought to involve several neuroplastic changes in multiple brain regions, resulting in distorted pain perception and associated comorbidities. While the functional changes in the insula are recognized contributors to TNP, the intricate mechanisms underlying the involvement of the insula in TNP processing remain subjects of ongoing investigation. Here, we have overviewed the most recent advancements regarding the functional role of IC in regulating TNP alongside insights into the IC's connectivity with other brain regions implicated in trigeminal pain pathways. In addition, the review examines diverse modulation strategies that target the different parts of the IC, thereby suggesting novel diagnostic and therapeutic management of chronic TNP in the future.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11084050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140904480","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}