Journal of Headache and Pain最新文献

{"title":"Activation of central and peripheral transient receptor potential melastatin 8 increases susceptibility to spreading depolarization and facilitates trigeminal neuroinflammation.","authors":"Tzu-Ting Liu, Pin-Yu Chen, Chyun-Yea Tseng, Yun-Ning Chen, Jian-Bang Chen, Tz-Han Ni, Shuu-Jiun Wang, Shih-Pin Chen, Jiin-Cherng Yen","doi":"10.1186/s10194-025-01997-2","DOIUrl":"10.1186/s10194-025-01997-2","url":null,"abstract":"<p><strong>Background: </strong>Transient receptor potential melastatin 8 (TRPM8), a gene encoding a nonselective cation channel responsive to cold stimuli, has been implicated in migraine susceptibility. Despite this association, the role of TRPM8 to migraine pathogenesis remains elusive. This study aims to elucidate the potential role of TRPM8 in migraine pathophysiology.</p><p><strong>Methods: </strong>TRPM8 expression in the cortex and primary trigeminal ganglion (TG) cells was analyzed via immunostaining. The central role of TRPM8 was assessed using a spreading depolarization (SD) model, where intracerebroventricular injections or topical applications of TRPM8 agonists and antagonists were administered to rats to investigate their effects on KCl-evoked SD and SD-induced cortical inflammation. The peripheral role of TRPM8 in migraine was evaluated using primary cultures of rat TG cells by analyzing the effects of TRPM8 activation on calcitonin gene-related peptide (CGRP) expression, release, and trigeminal neuroinflammation.</p><p><strong>Results: </strong>TRPM8 was homogeneously distributed in the cerebral cortex, predominantly co-localizing with cortical neurons. Activation of cortical TRPM8 increased the frequency of KCl-evoked SD and exacerbated SD-induced cortical inflammation. Interestingly. Interestingly, inhibition of cerebral TRPM8 had negligible effects. In TG primary cultures, TRPM8 activation upregulated CGRP expression and release and induced cyclooxygenase-2 (Cox2) upregulation via a calmodulin kinase II (CaMKII)-dependent mechanism.</p><p><strong>Conclusions: </strong>TRPM8 activation increased susceptibility to SD and facilitated the effects of CGRP and trigeminal neuroinflammation, implicating that TRPM8 may contribute to migraine pathophysiology through central and peripheral mechanisms.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"55"},"PeriodicalIF":7.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634102","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":"Neuroimaging differences between chronic migraine with and without medication overuse headache: a 7 Tesla multimodal MRI study.","authors":"Yin Sun, Longteng Ma, Song Wang, Caohui Duan, Xinyu Wang, Xiangbing Bian, Shuqing Wang, Deqi Zhai, Siyuan Xie, Shuhua Zhang, Yingyuan Liu, Xiaoxue Lin, Ruobing Wang, Xiu Liu, Shengyuan Yu, Xin Lou, Zhao Dong","doi":"10.1186/s10194-025-01988-3","DOIUrl":"10.1186/s10194-025-01988-3","url":null,"abstract":"<p><strong>Background: </strong>Chronic migraine (CM) patients with medication overuse headache (MOH) exhibit distinct neurobiological alterations compared to those without MOH. However, prior studies, often limited to single imaging modalities, have yielded inconsistent findings. This study employs multimodal MRI-combining structural, diffusion tensor, and functional imaging-to characterize brain abnormalities in CM patients with and without MOH, while investigating the relationship between acute analgesic use frequency and these changes.</p><p><strong>Methods: </strong>The study employed comparative analyses to examine differences in gray matter volume, white matter integrity, and spontaneous brain activity between CM patients with (CM + MOH) and without (CM - MOH) medication overuse headache, as well as healthy controls. Additionally, brain regions associated with the frequency of acute medication use were identified and further investigated.</p><p><strong>Results: </strong>Nineteen CM - MOH patients, twenty-five CM + MOH patients, and nineteen healthy controls were enrolled. Compared to CM - MOH patients, CM + MOH patients exhibited significantly reduced gray matter volume in the parahippocampal gyrus and middle occipital gyrus, alongside markedly lower fractional anisotropy (FA) in the left cingulum bundle. Moreover, fractional amplitude of low-frequency fluctuations (fALFF) values in the right putamen were significantly decreased and demonstrated a negative correlation with the frequency of acute pain medication use. Functional connectivity analysis further revealed significantly enhanced connectivity between the right putamen and regions such as the frontal lobe, middle cingulate gyrus, lingual gyrus, and precuneus, which positively correlated with the frequency of acute analgesic use.</p><p><strong>Conclusion: </strong>Compared to CM - MOH patients, those with MOH exhibit distinct patterns of gray matter volume reduction in regions associated with memory and visual processing, accompanied by significant white matter disruption. Additionally, decreased spontaneous activity in the right putamen and heightened functional connectivity between the putamen and multiple brain regions are strongly correlated with the frequency of acute medication use. These results highlight the significant impact of medication overuse on brain structure and function, shedding light on the mechanisms of migraine chronification.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"54"},"PeriodicalIF":7.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624767","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":"Headache types and characteristics in patients with Amyotrophic Lateral Sclerosis.","authors":"Radwa Soliman, Nagia Fahmy, Mahmoud S Swelam","doi":"10.1186/s10194-025-01987-4","DOIUrl":"10.1186/s10194-025-01987-4","url":null,"abstract":"<p><strong>Background: </strong>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder associated with progressive loss of motor neurons, this result in muscle denervation, atrophy and consequently death takes place due to respiratory failure within 3-5 years of onset of symptoms.</p><p><strong>Our aim: </strong>Was to investigate types and frequency of headache in ALS patients.</p><p><strong>Methods: </strong>This is cross sectional hospital based study. Clinically definite 100 ALS Patients (diagnosed according to El Escorial revised criteria) were recruited out of 137 ALS patients presented to the Neuromuscular Clinic in Ain Shams university Hospital from February 2022 to June 2024. Patients were screened for headache types and symptoms diagnosed according to International Headache Society criteria (IHS). Headache severity and impact were assessed using Arabic versions of Headache Impact Test (HIT) and Migraine Disability Assessment (MIDAS). Depression was also assessed via Arabic version of Beck's Depression Inventory (BDI). ALS symptoms severity was assessed via Arabic version of Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R). Cognitive functions were assessed via the Egyptian version of the Edinburgh Cognitive and Behavioral Amyotrophic Lateral Sclerosis Screen (ECAS‑EG). Demographic data and ALS related parameters were collected.</p><p><strong>Results: </strong>Among 100 patients with clinically definite ALS, 79 patients reported headaches, 62 of them had primary headaches; with tension-type headache being the most commonly reported in 46 patients, Migraine in 16 patients. Fifteen ALS patients had secondary headaches; among them 12 had headache secondary to respiratory insufficiency and 3 patients developed headache after the initiation of Riluzole therapy. Two patients had non specific headache. Mean age for the patients at ALS presentation was 43.9 ± 13.8, Mean ALSFRS-R score 33.3 ± 9.04. The relationships between headache and clinical features of ALS were also investigated.</p><p><strong>In conclusion: </strong>ALS patients should be evaluated for Headache; Not only headache secondary to respiratory compromise and hypercapnea, but also primary headaches which can be overlooked in patients with ALS.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"53"},"PeriodicalIF":7.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11900350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615639","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":"Temporomandibular disorders and mental health: shared etiologies and treatment approaches.","authors":"Jiamin Wan, Jiu Lin, Tingfeng Zha, Francisco Ciruela, Shaokang Jiang, Zuping Wu, Xinyi Fang, Qianming Chen, Xiaoyan Chen","doi":"10.1186/s10194-025-01985-6","DOIUrl":"10.1186/s10194-025-01985-6","url":null,"abstract":"<p><p>The biopsychosocial model suggests that temporomandibular disorders (TMDs) often coexist with mental health disorders, particularly depression and anxiety, affecting a significant portion of the global population. The interplay between TMDs and mental health disorders contributes to a complex comorbidity, perpetuating a cycle of mutual influence and reinforcement. This review investigates the neurobiological mechanisms and epidemiological evidence supporting the shared etiology of TMDs and mental health disorders, exploring potential shared vulnerabilities and bidirectional causal relationships. Shared vulnerabilities between TMDs and mental health disorders may stem from genetic and epigenetic predispositions, psychosocial factors, and behavioral aspects. Inflammatory cytokines, neurotransmitters, neurotrophins, and neuropeptides play pivotal roles in both peripheral and central sensitization as well as neuroinflammation. Brain imaging studies suggest that TMDs and mental health disorders exhibit overlapping brain regions indicative of reward processing deficits and anomalies within the triple network model. Future research efforts are crucial for developing a comprehensive understanding of the underlying mechanisms and confirming the reciprocal causal effects between TMDs and mental health disorders. This review provides valuable insights for oral healthcare professionals, stressing the importance of optimizing treatment strategies for individuals dealing with concurrent TMDs and mental health issues through a personalized, holistic, and multidisciplinary approach.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"52"},"PeriodicalIF":7.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11899861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615640","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 and continuability of 675 mg fremanezumab administration over 2 years.","authors":"Shohei Yoshida, Noboru Imai, Masato Keicho, Jun Kamimura, Asami Moriya, Nobuyasu Yagi, Rieko Suzuki, Takashi Konishi, Masahiro Serizawa","doi":"10.1186/s10194-025-01994-5","DOIUrl":"10.1186/s10194-025-01994-5","url":null,"abstract":"<p><strong>Background: </strong>Real-world data on the long-term adherence to- and efficacy of fremanezumab 675 mg quarterly dosing remain scarce. Our study evaluated the efficacy of- and patient adherence to 675 mg fremanezumab for episodic migraine (EM) and chronic migraine (CM) over 2 years and analyzed the reasons for discontinuation.</p><p><strong>Methods: </strong>Among patients attending our headache outpatient clinic, those aged ≥ 15 years who commenced fremanezumab 675 mg quarterly dose schedule from November 2021 to June 2022 were enrolled in this single-center observational study. The frequency and severity of headaches were recorded using a headache diary. The observation period ended for each patient at 24 months after treatment initiation. The reasons for discontinuation were documented based on follow-up medical records.</p><p><strong>Results: </strong>Twenty-eight patients were enrolled, of whom 15 had CM and 13 had EM. One patient with CM was excluded due to withdrawal after the first injection. Of the 27 remaining patients, the treatment was effective in 70.4% (n = 19). 44.4% (n = 12) continued fremanezumab 675 mg until study termination. Among those patients who remained on fremanezumab for two years, seven updated the monthly headache calendars consistently: 2 had CM, and 5 had EM. Mean changes in MMD from the baseline were - 2.2 at 3 months,, -1.8 at 12 months, and - 1.6 (SD = 3.0) at 2 years. Treatment was discontinued because of sustained improvement in 25.9% (n = 7). 22.2% of cases (n = 6) experienced insufficient effectiveness, resulting in discontinuation. One patient (3.7%) discontinued because of injection-site erythema. One patient (3.7%) was discontinued because of pregnancy. Among the non-responders, three switched from fremanezumab to erenumab, with one returning to fremanezumab at a monthly injection of 225 mg after efficacy with erenumab waned. Two patients switched to galcanezumab. All patients who switched medication continued the new medication owing to its effectiveness. One patient was lost to follow-up.</p><p><strong>Conclusions: </strong>Fremanezumab 675 mg quarterly dose effectively reduces headache frequency over an extended period and may facilitate medication cessation in patients who experience substantial recovery.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"51"},"PeriodicalIF":7.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604996","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":"Offset analgesia as a marker of dysfunctional pain modulation in episodic and chronic migraine.","authors":"Giuseppe Cosentino, Elisa Antoniazzi, Camilla Cavigioli, Elena Guaschino, Natascia Ghiotto, Matteo Castaldo, Massimiliano Todisco, Roberto De Icco, Cristina Tassorelli","doi":"10.1186/s10194-025-01995-4","DOIUrl":"10.1186/s10194-025-01995-4","url":null,"abstract":"<p><strong>Background: </strong>The offset analgesia phenomenon refers to the disproportionately large decrease in the perceived pain following a slight decrease in intensity of a noxious heat stimulus. It is considered an expression of the activation of the endogenous pain-modulation system. The main aim of this study was to examine pain processing using the offset analgesia paradigm in subjects with interictal episodic migraine compared to those with non-ictal chronic migraine. Additionally, as secondary outcome measures, we aimed to: (1) explore fluctuations in the endogenous pain modulation system throughout the migraine cycle by including small subgroups of episodic migraine patients in different migraine phases, and (2) compare different subgroups of non-ictal chronic migraine patients with or without medication overuse headache (MOH).</p><p><strong>Methods: </strong>A total of 68 subjects with episodic migraine (different subjects were evaluated during the interictal, preictal, ictal, or postictal phase), 34 with non-ictal chronic migraine with or without MOH, and 30 healthy controls were enrolled. Participants underwent six trials involving constant temperature and stimulus offset applied to the forehead, with pain responses measured using a continuous analogue-to-digital converter of VAS.</p><p><strong>Results: </strong>The offset analgesia phenomenon was recorded predominantly during the postictal phase among the population of episodic migraine patients, as well as in healthy subjects. Offset analgesia was generally absent in interictal episodic migraine subjects and in subjects with chronic migraine with MOH, though some individual variability was observed. A paradoxical increase in pain facilitation was observed in most preictal and ictal episodic migraine subjects, as well as in chronic migraine subjects without MOH. The severity of offset analgesia impairment correlated with scores on the Allodynia Symptom Checklist and the Numeric Pain Rating Scale, which assessed average headache intensity during untreated migraine attacks.</p><p><strong>Conclusions: </strong>Episodic and chronic migraine patients exhibit disrupted top-down pain modulation pathways, with more significant alterations in chronic migraine without MOH. Additionally, we provide preliminary evidence that cyclical changes in the endogenous pain modulation system could contribute to migraine recurrence in episodic migraine sufferers. However, given the small subgroups of interictal patients evaluated in different migraine phases and the cross-sectional study design, these findings should be interpreted with caution and confirmed by future longitudinal studies with larger sample sizes.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"50"},"PeriodicalIF":7.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596885","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 tension-type headache in Asia from 1990 to 2021.","authors":"Yingzhu Zhao, Yujie Yi, Hong Zhou, Qian Pang, Jie Wang","doi":"10.1186/s10194-025-01990-9","DOIUrl":"10.1186/s10194-025-01990-9","url":null,"abstract":"<p><strong>Background: </strong>In recent years, headache diseases have spread throughout the world, causing great suffering and even severe disability to patients, and increasing the burden on health care systems. However, studies of specific regions are rare. The purpose of our study is to comprehensively analyze the current situation and trends of headache diseases in Asia between 1990 and 2021, to provide details of headache diseases in Asia, and to provide scientific data to support health development strategies.</p><p><strong>Methods: </strong>Data from the Global Burden of Disease (GBD) 2021 database were used to calculate the incidence, prevalence and disability-adjusted life years (DALYs) of headache disorders in Asia from 1990 to 2021. Differences between years, ages, sexes and countries were also assessed, and we evaluated the correlation between epidemiological and sociodemographic indices (SDIs).</p><p><strong>Result: </strong>In 2021, there were approximately 683,514,637 cases of migraine in Asia. Meanwhile, there are now 1,130,221,326 cases associated with tension-type headache (TTH) in Asia. Specifically, the age-standardized DALYs (ASDR) [607 cases per 100,000 people (95% UI: 70 - 1,363)] for migraine were highest in Southeast Asia, and the ASDR [422 cases per 100,000 people (95% UI: 86-938)] was lowest in high-income countries of the Asia-Pacific region. ASDR [67 cases per 100,000 people (95% UI: 18-236)] was highest for TTH in Central Asia and lowest for ASDR [43 cases per 100,000 people (95% UI: 13-141)] in East Asia. In addition, women are the key population for migraine and TTH prevalence. In Asia, there were negative and positive correlations between migraine and TTH and SDI, respectively.</p><p><strong>Conclusions: </strong>Headache disorders pose a serious threat to the quality of life and safety of patients in Asia, increasing the burden on society, and this impact will continue to grow. Our findings suggest that active public awareness, improved guidelines, and better disease management are necessary to expand the public and healthcare system's attention to headache disorders, and thereby gain a greater advantage in combating the burden of headache disorders in the future.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"49"},"PeriodicalIF":7.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596890","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 efficacy and safety of zavegepant nasal inhalation versus oral calcitonin-gene related peptide receptor antagonists in the acute treatment of migraine: a systematic review and network meta-analysis of the literature.","authors":"Zixiang Zhu, Yanbing Tang, Longyuan Li, Hanyu Ni, Meirong Liu, Zhouqing Chen, Zhong Wang","doi":"10.1186/s10194-025-01984-7","DOIUrl":"10.1186/s10194-025-01984-7","url":null,"abstract":"<p><strong>Background: </strong>The latest randomized controlled trial (RCT) revealed that zavegepant, a new nasal inhalation calcitonin gene-related peptide (CGRP) receptor antagonist, has a clear efficacy in the acute treatment of migraine. However, whether the efficacy of this new nasal inhalation drug is better than other oral CGRP receptor antagonists remained to be confirmed. Therefore, we designed this network meta-analysis (NMA) to provide a reference for the clinical application of zavegepant.</p><p><strong>Methods: </strong>We systematically searched PubMed, EMBASE, The Cochrane Register of Controlled Trials, Scopus, and Web of Science up to December 1, 2024. RCTs using CGRP receptor antagonists (excluding non-randomized, non-English or no extractable data trials) to treat adult patients suffering from acute migraine were included. STATA 18.0 and R STUDIO were used for the statistical analysis.</p><p><strong>Results: </strong>A total of 15 randomized clinical trials with 11,179 patients were included. Compared with the placebo, zavegepant 10 mg demonstrated a significantly higher efficiency for pain freedom at 2 h (relative risk (RR) = 1.54, 95% CI: 1.28-1.82, I² = 0.0%, P < 0.001) and most bothersome symptom (MBS) freedom at 2 h (RR = 1.26, 95% CI: 1.13-1.42, I² = 0.0%, P < 0.001), but did not show significant superiority over oral CGRP receptor antagonists. In terms of safety, zavegepant 10 mg was significantly inferior to placebo but not inferior to oral CGRP receptor antagonists.</p><p><strong>Conclusion: </strong>Zavegepant 10 mg can quickly relieve symptoms and has no significant difference in safety compared with oral drugs, which can provide rapid and safe efficacy in the acute treatment of migraine. However, compared with other oral CGRP receptor antagonists, zavegepant 10 mg by nasal inhalation has no obvious advantage in long-term symptom relief rate.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"48"},"PeriodicalIF":7.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596892","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":"Exploring vestibulocerebellum-vestibular nuclei-spinal trigeminal nucleus causals communication and TRPV2 ion channel in a mouse model of vestibular migraine.","authors":"Qingling Zhai, Qihui Chen, Ning Zhang, Hongyan Li, Qijun Yu, Yonghui Pan","doi":"10.1186/s10194-025-01986-5","DOIUrl":"10.1186/s10194-025-01986-5","url":null,"abstract":"<p><strong>Background: </strong>Vestibular migraine (VM) is a disorder characterized by recurrent episodes of dizziness or vertigo and is often accompanied by headache. The mechanisms underlying vestibular dysfunction and pain in VM remain unclear.</p><p><strong>Methods: </strong>Chronic migraine (CM) and VM models were induced by NTG and kainic acid, respectively. Behavioral assessments were conducted to evaluate vestibular dysfunction and pain in the VM and CM models. Transmission electron microscopy (TEM) was used to examine peripheral receptor impairment. Immunofluorescence, including staining for Cellular Proto-oncogene (c-Fos), Neuronal Nuclei (NeuN), and calcitonin gene-related peptide (CGRP), identified activated brain regions such as the cortex, midbrain, and cerebellum. Multiplex immunohistochemistry and cholera toxin subunit B (CTB) tracing were performed to analyze nuclear heterogeneity and neural communication. Additionally, RNA sequencing (RNA-Seq) and Ionized calcium-binding adapter molecule 1 (IBA1) immunostaining were used to investigate ion channel expression in the spinal trigeminal nucleus caudalis (Sp5c).</p><p><strong>Results: </strong>CM and VM-related behaviors, such as allodynia and balance disturbance, were successfully reproduced in mouse model. TEM revealed significant damage to peripheral sensory receptors, particularly in the trigeminal ganglion and cochlear cells. Distinct activation patterns of c-Fos and CGRP were observed in VMs and CMs. CTB tracing confirmed that signals are transmitted from the vestibulocerebellum (VbC) to the Sp5c via the vestibular nuclei (VN). Furthermore, RNA-Seq combined with coimmunostaining revealed an increased expression of transient receptor potential vanilloid 2 (TRPV2) ion channels in microglia within Sp5c, indicating their potential role in VM pathology.</p><p><strong>Conclusions: </strong>This study preliminarily explored VbC-VN-Sp5c communication and identified TRPV2 ion channels in microglia as key players in neuron-glia crosstalk in VM. These findings provide new insights into the mechanisms underlying vestibular migraine and suggest potential therapeutic targets.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"47"},"PeriodicalIF":7.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567376","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":"Advances in GLP-1 receptor agonists for pain treatment and their future potential.","authors":"Yongtao He, Biao Xu, Mengna Zhang, Dan Chen, Shuyuan Wu, Jie Gao, Yongpeng Liu, Zixin Zhang, Junzhe Kuang, Quan Fang","doi":"10.1186/s10194-025-01979-4","DOIUrl":"10.1186/s10194-025-01979-4","url":null,"abstract":"<p><p>Glucagon-like peptide-1 receptor agonists (GLP-1RAs) show substantial efficacy in regulating blood glucose levels and lipid metabolism, initially as an effective treatment for diabetes mellitus. In recent years, GLP-1RAs have become a focal point in the medical community due to their innovative treatment mechanisms, robust therapeutic efficacy, and expansive development prospects. Notably, GLP-1RAs benefit pain management through their neuroprotective and metabolic regulatory properties, such as inhibiting inflammation responses and oxidative stress, promoting β-endorphin release and modulating several other crucial biological pathways. Hence GLP-1RAs hold promise for repurposing as treatments for pain disorders. In this narrative review, we thoroughly trace the current preclinical and clinical evidence of seven pain modalities, including inflammatory pain, osteoarthritis, visceral pain, neuropathic pain, diabetic neuropathy, cancer pain and headache, to support the efficacy and underlying biological mechanisms of GLP-1RAs as therapeutic agents for pain suffering. Despite these promising findings, further research is necessary to establish their long-term efficacy, optimal dosing strategies, and potential synergistic interactions of GLP-1RAs with existing pain management therapies. Future clinical trials should aim to distinguish the direct analgesic effects of GLP-1RAs from their metabolic benefits and explore their broader applications in pain conditions. The ongoing exploration of new indications for GLP-1RAs further highlights their transformative potential in advancing medical treatments across diverse clinical fields.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"46"},"PeriodicalIF":7.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522853","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}