Cephalalgia最新文献

{"title":"Reaching international consensus on the definition of refractory migraine using the Delphi method.","authors":"Jennifer Robblee, Fawad A Khan, Michael J Marmura, Hope L O'Brien, Lawrence D Robbins, Marielle Kabbouche Samaha, Morris Levin, Simona Sacco, Raffaele Ornello, Stephanie J Nahas, Heike Hesse, Annika Ehrlich, Adam S Sprouse-Blum, Christina Sun-Edelstein, Bronwyn Jenkins, Elizabeth K Seng, Shivang Joshi, Meredith J Barad, Mi Ji Lee, Sheena K Aurora, Mario Fernando Prieto Peres","doi":"10.1177/03331024251367767","DOIUrl":"https://doi.org/10.1177/03331024251367767","url":null,"abstract":"<p><p>AimDespite its frequency in tertiary headache centers, the International Classification of Headache Disorders, 3rd edition (ICHD-3) does not include refractory migraine. Multiple definitions have been proposed with a recent 2020 proposal for both refractory migraine and resistant migraine by the European Headache Federation (EHF). The aim is to reach an international consensus on the definition of refractory migraine.MethodsThis study is a Delphi consensus carried out by a group of international experts in headache medicine. Following a focus group, a panel of 20 experts and one facilitator reviewed the EHF proposed criteria to build upon their definitions. The Delphi consensus was conducted across five rounds. Questions with >70% consensus were deemed to have strong agreement, 60-70% consensus was deemed minor agreement, and <60% deemed no agreement. A final meeting was held to discuss any concerns and specific wording.ResultsThe Delphi consensus led to the development of four key categories: refractory migraine, probable refractory migraine, resistant migraine, and treatment-responsive migraine. Similar to the EHF 2020 definitions, refractory migraine requires treatment failure of all evidence-based classes, and resistant migraine requires failure of at least three classes. Probable refractory migraine criteria were designed to account for situations where treatment access barriers may prevent trials of certain medication classes (e.g. pediatrics, low to middle-income countries, lack of insurance coverage). Finally, treatment-responsive migraine criteria were developed to allow for standardization in research studies comparing refractory or resistant migraine to migraine that is treatment-responsive.ConclusionsThese four categories may aid in enrollment for studies on pathophysiology, biomarkers, and new treatment targets. Clinically, the criteria for refractory and resistant migraine will help with clinical decision-making by reinforcing the need to try evidence-based treatments and by providing guidance regarding when to try more aggressive treatment approaches. These criteria may also increase attention to this population's disease burden to help advocate for them as a specific migraine subgroup. Field testing in diverse clinical settings will be needed, but it is recommended that ICHD-3 considers inclusion of these four categories in their appendix.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 9","pages":"3331024251367767"},"PeriodicalIF":4.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dorso lateral prefrontal cortex stimulation with TMS in chronic migraine individuals refractory to anti-CGRP monoclonal antibodies: Clinical, neuropsychological and neurophysiological effects.","authors":"Livio Clemente, Giulia Paparella, Stefania Scannicchio, Chiara Abbatantuono, Giusy Tancredi, Emanuella Ladisa, Marianna D Delussi, Elena Ammendola, Addolorata Maria Pia Prudenzano, Marina de Tommaso","doi":"10.1177/03331024251364843","DOIUrl":"https://doi.org/10.1177/03331024251364843","url":null,"abstract":"<p><p>BackgroundPeople with high-frequency episodic migraine or chronic migraine may have resistant or refractory forms. The lack of efficacy of pharmacologic therapies is a major clinical challenge that requires alternative strategies, including neuromodulation and exploration of new targets to improve disease management. The present study aimed to test the effectiveness of an accelerated protocol of theta burst stimulation (iTBS) via the dorso lateral prefrontal cortex (DLPFC) in a group of chronic migraine individuals who did not respond to monoclonal antibodies against calcitonin gene-related peptide (CGRP). The co-primary outcomes were the reduction in monthly headache frequency, use of symptomatic medication and perceived pain intensity. In parallel we wanted to understand the possible role of the prefrontal cortex in the emotional and cognitive functions likely responsible for treatment failure and to offer a possible non-pharmacologic option to individuals with difficult-to-treat migraine. To this end, we measured clinical outcomes along with an electroencephalogram (EEG) and behavioral responses to cognitive and emotional tests related to prefrontal functions.MethodsThis study was conducted in a controlled, single-blind design in 12 people with chronic refractory migraine. An accelerated protocol of iTBS on DLPFC was preceded by a sham session and followed by a two-month follow-up. Clinical data were collected and a neuropsychological assessment including anxiety, depression and cognitive profile was performed. Cognitive and emotional Stroop testing was performed at baseline, after sham and real stimulation, and at follow-up during high-density EEG recording to obtain event-related potentials (N2, N400 and late sustained potential (LP)). Stroop data from an age- and sex-matched control group were compared with those of migraine individuals.ResultsMonthly headache days, monthly medication days and headache intensity improved after real stimulation. A similar trend emerged for anxiety, depression, and cognitive performance. The Stroop test was impaired in the baseline, as evidenced by an increase in reaction time and a decrease in N2 and LP in the cognitive task, which returned to normal after real iTBS and at follow-up.ConclusionsThe results support the efficacy of iTBS as a non-invasive neuromodulation approach for the treatment of chronic, refractory migraine. They tentatively point to the role of cognitive fog and psychopathological symptoms in refractoriness to anti-CGRP drugs, which should be confirmed in larger multicenter studies, and suggest this non-pharmacological approach as another promising therapeutic option for people with difficult-to-treat migraine.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 9","pages":"3331024251364843"},"PeriodicalIF":4.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact and care gaps of headache disorders in active-duty military personnel: A cross-sectional study from a European armed forces population.","authors":"Carl H Göbel, Ursula Müller, Hanno Witte, Katja Heinze-Kuhn, Axel Heinze, Anna Cirkel, Hartmut Göbel","doi":"10.1177/03331024251374310","DOIUrl":"10.1177/03331024251374310","url":null,"abstract":"<p><p>AimPrimary headache disorders such as migraine and tension-type headache are highly prevalent in military populations and may severely impact operational performance and readiness. Despite this, data from many European armed forces are lacking. This study investigates headache phenotypes, diagnosis, treatment and functional impairment in active-duty personnel of a major European military organization.MethodsThis cross-sectional cohort study utilized an anonymous 33-item online questionnaire distributed across military medical centers in Germany between May and July 2023. The survey assessed demographics, headache types according to the International Classification of Headache Disorders, 3rd edition (ICHD-3), diagnostic awareness, treatment history and headache-related disability using the Migraine Disability Assessment Score (MIDAS).ResultsOf the 1189 participants, 914 (77%) completed the survey. Among them, 839 (94.9%) reported experiencing headaches in the past 12 months. Based on ICHD-3 criteria, 227 individuals (27.1%) met the complete set of criteria for migraine, while 246 (29.2%) were classified as probable migraine. Tension-type headache was reported by 222 respondents (26.5%), and cluster headache was resported by 34 (4.1%). Notably, 61.4% of participants had never received a formal diagnosis and only 38.6% had ever sought medical care for their headaches. Functional impairment was substantial: 63.8% reported losing at least one workday in the past three months due to headache. Among those with migraine, an average of 3.9 workdays per month were lost. Despite this burden, only 27.3% of individuals with migraine had ever used preventive medication.ConclusionsPrimary headache disorders are common, underdiagnosed and inadequately treated in this military population, leading to significant functional and operational impairment. Our findings underscore the urgent need for improved screening, diagnosis and evidence-based treatment strategies in uniformed health systems. The results may inform similar efforts in other military and high-demand occupational settings.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 9","pages":"3331024251374310"},"PeriodicalIF":4.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The spectrum of migraine aura: Towards a precise phenotypic classification.","authors":"Michele Viana, Mario Fernando Prieto Peres","doi":"10.1177/03331024251372621","DOIUrl":"https://doi.org/10.1177/03331024251372621","url":null,"abstract":"<p><p>IntroductionTypical migraine aura is characterized by transient focal neurologic symptoms, visual, sensory, dysphasic or other higher cortical dysfunctions. Their manifestations are multi-faceted, with inter and intra-variability.ObjectiveTo provide a narrative review describing contributions that assist in achieving a precise phenotypic classification of migraine aura.MethodsWe conducted a comprehensive review of the literature to identify and analyze the full spectrum of migraine aura variables. Based on the findings, we proposed a prospective diary model for systematically recording these elements in clinical or research settings.ResultsVisual symptoms are the most multifaceted with many peculiarities such as quality (26 elementary visual symptoms have been described), colour, intermittence, localization and laterality in visual field and direction of spreading. Sensory and dysphasic symptoms have lower level of complexity. The combinations of symptoms, such as their time relationships or duration, are also extremely variable. Furthermore, headache can have five different patterns of presentation with respect to aura onset/end. Higher cortical dysfunctions need to be further investigated in wider populations. After collecting the full spectrum of migraine aura features, we created a diary which we propose can prospectively record those variables.ConclusionThe findings of this review show that migraine auras present a wide and multi-faceted spectrum of symptoms, generating hundreds of possible scenarios. Therefore, a detailed aura diary to complete during attacks will be of utmost importance to move toward a precise phenotypic classification.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 9","pages":"3331024251372621"},"PeriodicalIF":4.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atogepant for the preventive treatment of episodic migraine in Japanese participants: A phase 2/3, randomized, double-blind, placebo-controlled trial with an active treatment extension (RELEASE).","authors":"Yasuhiko Matsumori, Hiroshi Yamada, Yoshishige Nagaseki, Kazutaka Shimizu, Krisztian Nagy, Ryotaro Matsuzawa, Tetsuya Otani, Molly Yizeng He, Hua Guo, Gina Ahmadyar, Takao Takeshima","doi":"10.1177/03331024251374569","DOIUrl":"https://doi.org/10.1177/03331024251374569","url":null,"abstract":"<p><p>BackgroundAtogepant is an oral calcitonin gene-related peptide receptor antagonist approved in the US and EU for the preventive treatment of migraine in adults. We evaluated the efficacy, safety, and tolerability of atogepant for the preventive treatment of episodic migraine (EM) in Japanese participants.MethodsRELEASE was a phase 2/3, multicenter, randomized, double-blind, placebo-controlled study enrolling adult participants with a ≥1-year history of migraine, <50 years of age at time of migraine onset, history of 4-14 monthly migraine days (MMDs), and <15 monthly headache days in the three months prior to screening and during the screening/baseline period. The study included a four-week screening/baseline period, 12-week double-blind treatment period (DBTP), 12-week active treatment extension period, and 30-day safety follow-up. Participants were randomized 1:1:1:1 to placebo, atogepant 10 mg once daily (QD), 30 mg QD, or 60 mg QD for the 12-week DBTP. Completers of the DBTP could continue to the 12-week active treatment extension period where the placebo group was rerandomized 1:1:1 to atogepant 10 mg, 30 mg, or 60 mg; atogepant groups continued the same dose. The primary endpoint was the change from baseline in mean MMDs across the 12-week DBTP.ResultsOf 807 participants screened, 523 were treated in the 12-week DBTP (Safety Population 1 [placebo, N = 134; atogepant 10 mg, N = 126; 30 mg, N = 131; 60 mg, N = 132]; modified intent-to-treat population [placebo, N = 133; atogepant 10 mg, N = 127; 30 mg, N = 130; 60 mg, N = 131]). The least square mean difference (95% confidence interval) from placebo in mean MMDs across 12 weeks was -1.57 (-2.24, -0.89) for atogepant 10 mg, -1.90 (-2.57, -1.22) for 30 mg, and -2.10 (-2.78, -1.43) for 60 mg (all <i>p</i> < 0.0001). Treatment-emergent adverse events (TEAEs) in the DBTP occurred in 46.3%, 45.2%, 38.9%, and 43.2% of participants receiving placebo, atogepant 10 mg, 30 mg and 60 mg, respectively. During the DBTP, TEAEs occurring ≥5% were constipation and nasopharyngitis, and there was one serious TEAE in the atogepant 10 mg group considered not related to treatment. TEAEs resulting in treatment discontinuation were infrequent in all treatment groups in the DBTP. Safety was consistent in the 12-week active treatment extension period.ConclusionsAtogepant treatment demonstrated statistically significant and clinically meaningful reductions in mean MMDs compared with placebo across the 12-week DBTP in Japanese participants with EM. The safety profile of atogepant in Japanese participants was consistent with the known safety profile in the global population. No new safety signals were identified.Trial registrationClinicalTrials.gov NCT05861427; https://clinicaltrials.gov/study/NCT05861427.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 9","pages":"3331024251374569"},"PeriodicalIF":4.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimising combined treatment for migraine and temporomandibular disorders (TMDs).","authors":"Marcela Romero-Reyes, Simon Akerman, Alan M Rapoport","doi":"10.1177/03331024251368882","DOIUrl":"10.1177/03331024251368882","url":null,"abstract":"<p><p>Temporomandibular disorders (TMDs) and migraine are highly prevalent, overlapping pain conditions that cause considerable burden in the population. These two disorders are of different etiology and pathophysiology, but both are mediated by the trigeminal system. Due to the interrelated anatomy and physiology of the craniofacial and cervical structures, shared molecular links and mutual feedback, there is an inherent potential for exacerbation of symptomatology, perpetuation and progression; however, on a positive note, there is good potential for developing integrated, mutually beneficial management protocols when migraine and TMDs are comorbid. Currently, there are no established protocols of management, and the literature is limited in studies exploring dual therapeutic protocols. So, the question is, how can management be optimized with the evidence available? We should start by recognizing the need for multidisciplinary management to improve patient outcomes and we must highlight the importance of the dialogue between headache medicine and dentistry. The meeting point is where the dental discipline and the specialty of orofacial pain reside. The underlying pathophysiology of this comorbidity points to the need to decrease mutual exacerbation inputs. Therefore, it is fundamental to identify contributing factors of potential sensitization, such as the presence of parafunctional behaviors, cervical spine contributors, the presence of other comorbidities and headache hygiene. Current evidence supports management recommendations that should be developed by a multidisciplinary team as an integrated plan with combination therapy including both pharmacological and non-pharmacological approaches to optimize management. This multidisciplinary team should include the medical provider (neurologist/headache medicine expertise), the dentist specialized in orofacial pain, the physical therapist and the behavioral medicine specialist. Research is needed to support evidence-based integrated protocols for the management of comorbid migraine and TMDs. Evidence has shown that calcitonin gene-related peptide (CGRP) is also involved in TMDs. CGRP-targeting therapies may hold future opportunities for pharmacological monotherapy addressing this comorbidity.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 9","pages":"3331024251368882"},"PeriodicalIF":4.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain imaging in migraine with and without aura: Similarities and differences.","authors":"Francesco Casillo, Gabriele Sebastianelli, Chiara Abagnale, Antonio Di Renzo, Lucia Ziccardi, Vincenzo Parisi, Gianluca Coppola","doi":"10.1177/03331024251365807","DOIUrl":"10.1177/03331024251365807","url":null,"abstract":"<p><p>BackgroundWhether migraine with aura (MA) is a biologically independent entity from migraine without aura (MO) is still debated. Similarities and differences between MO and MA have been extensively investigated in recent years through several neuroimaging studies, providing valuable insights into their underlying pathophysiology. To provide a better understanding of functional and structural differences between MO and MA, we conducted a narrative review of neuroimaging studies in these two conditions.MethodsA comprehensive PubMed search for neuroimaging studies in MO and MA was conducted in May 2025. We included studies that directly compared the two conditions using diffusion tensor imaging, voxel-based morphometry, surface-based morphometry, functional MRI and arterial spin labeling studies. No publication date restrictions were applied.ResultsOverall, patients with MA exhibited heightened engagement of the visual regions, cerebellum and thalamus. However, both MO and MA shared common activation of parts of the salience network and involvement of similar visual areas, including the striate and extrastriate cortices. However, contrasting results and several inconsistencies emerged from the analysis of different imaging studies. These included the lack of specification regarding the phase of the migraine cycle during which the scans were conducted, the inclusion of patients under migraine prevention, small sample sizes, and different approaches to data and statistical analysis (including a more liberal approach to interpreting results).ConclusionsAlthough several biases influence the reliability of most findings, patients with MA exhibited higher involvement of visual processing regions, decreased cerebellar antinociceptive activity and impaired thalamic information filtering. Whether this pattern represents the consequence of the recurrence of cortical spreading depression or a primary predisposition to it remains to be determined. Future studies with a rigorous and standardized approach are needed to understand the differences between MO and MA.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 9","pages":"3331024251365807"},"PeriodicalIF":4.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Greater occipital nerve injection with methylprednisolone as transitional therapy in episodic cluster headache: Results from an RCT.","authors":"Roemer B Brandt, Wim M Mulleners, Emile Couturier, Johannes A Carpay, Olivier H H Gerlach, Marieke Niesters, Joost Haan, Erik W van Zwet, Michel D Ferrari, Rolf Fronczek","doi":"10.1177/03331024251370324","DOIUrl":"10.1177/03331024251370324","url":null,"abstract":"<p><p>ObjectiveWe investigated whether greater occipital nerve injection (GON injection) with 80 mg of methylprednisolone at the onset of a cluster headache episode would reduce attack frequency faster than standard therapy with verapamil alone, and reduce the need for verapamil and the risk of adverse events (AEs).MethodsThis was an investigator-initiated, randomised, double-blind, 12-week clinical trial. Participants received GON injection with 80 mg of methylprednisolone (n = 36) or placebo (n = 34) within two weeks (median) after the onset of a cluster episode, followed by standard verapamil therapy and e-diary monitoring. The primary endpoint was the mean daily dose of verapamil over the entire 12-week study period. Key secondary endpoints were reduction in the mean daily dose of verapamil over the first four weeks and attack frequency reduction in the first week.ResultsIn the verum vs. placebo group, the mean daily dose of verapamil during the total 12-week study period did not differ (232 ± 188 mg vs. 244 ± 143 mg; Δ = 12 mg, 95% confidence interval (CI) = -68 to 92; <i>p</i> = 0.230). However, exploratory analysis of the secondary endpoints showed a lower verapamil dose in the first four weeks in the methylprednisolone group compared to placebo (227 ± 126 mg vs. 287 ± 107 mg; mean Δ 60 mg; 95% CI = -4 to -116), as was the median number of attacks at week 1 (7 (interquartile range = 2-11.75) vs. 10 (interquartile range = 6-17.5); 95% CI = -1.0 to -8.0), the mean attack intensity at week 1 (5.7 ± 1.9 vs. 6.6 ± 1.8; 95% CI = 0.0-1.8) and throughout the 12-week study period (5.0 ± 1.8 vs. 5.9 ± 1.9; 95% CI = 0.01-1.8), and the number of days with adverse events (455/2520 (18%) vs. 605/2850 (21%); p < 0.01). There were no serious AEs.ComclusionsThis study failed to establish its primary endpoint. However, exploratory analysis of the secondary endpoints revealed that GON injection with 80 mg of methylprednisolone at the beginning of a cluster headache episode followed by standard therapy verapamil is a safe transitional treatment that provides faster reduction in attack frequency and intensity than verapamil alone, decreases the mean verapamil dose over the first four weeks with consequently fewer adverse events in the first four weeks after the injection.Trial RegistrationThis study is registered on Clinicaltrials.gov with registration number NCT04014634 at 08-07-2019. First inclusion was on 30-07-2019.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 9","pages":"3331024251370324"},"PeriodicalIF":4.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The \"Migraines\" epidemic: Exposing the challenges of artificial intelligence in scientific writing.","authors":"Simona Sacco","doi":"10.1177/03331024251365833","DOIUrl":"https://doi.org/10.1177/03331024251365833","url":null,"abstract":"","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 8","pages":"3331024251365833"},"PeriodicalIF":4.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglial TRPV2-mediated neuroinflammation promotes central sensitization through microglial polarization in a vestibular migraine mouse model.","authors":"Qingling Zhai, Hongyan Li, Qihui Chen, Ning Zhang, Yanan Huang, Yonghui Pan","doi":"10.1177/03331024251364753","DOIUrl":"https://doi.org/10.1177/03331024251364753","url":null,"abstract":"<p><p>BackgroundNeuroinflammation, which is mediated by microglial activation, contributes to central sensitization, a key mechanism in vestibular migraine (VM). Transient receptor potential vanilloid 2 (TRPV2)-mediated calcium influx enhances nucleotide-binding oligomerization domain; leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome assembly, potentially driving inflammation. This study investigated the role of TRPV2 in VM pathogenesis.MethodsA VM model was established via repeated intraperitoneal injections of nitroglycerin and kainic acid-induced vestibular nerve terminal impairment. Periorbital thresholds and vestibular scores were measured to assess allodynia and vestibular dysfunction. Western blotting and immunofluorescence were used to evaluate TRPV2, ionized calcium-binding adapter molecule 1 (IBA1), interleukin-1β and NLRP3 expression in the spinal trigeminal nucleus caudalis (Sp5c) region. <i>In vitro</i>, BV2 cells treated with lipopolysaccharide and interferon-γ were transfected with TRPV2 small interfering RNA. TRPV2 activity was analyzed via patch-clamp electrophysiology. Microglial polarization and morphology were examined via flow cytometry and immunofluorescence, with a focus on CD16, CD63, CD206 and CD163 markers. NLRP3 inflammasome activation was assessed through western blotting and immunofluorescence.ResultsVM-related behaviors, including allodynia and dizziness, were successfully reproduced. Central sensitization in the Sp5c was marked by increased TRPV2 expression in microglia, as demonstrated by co-localization with the microglial marker IBA1. <i>In vitro</i>, TRPV2 inhibition in BV2 cells shifted microglial polarization from the pro-inflammatory M1 state to the anti-inflammatory M2 state. Additionally, TRPV2 blockade significantly reduced NLRP3 inflammasome activation and the levels of proinflammatory cytokines.ConclusionsTRPV2 regulates microglial activation and NLRP3 inflammasome activity via polarization mechanisms, contributing to central sensitization in VM. These findings highlight the critical role of TRPV2 in VM pathogenesis and its potential as a therapeutic target.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 8","pages":"3331024251364753"},"PeriodicalIF":4.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}