Pub Date : 2025-10-01Epub Date: 2025-10-08DOI: 10.1177/03331024251377753
Jes Olesen
IntroductionThe international headache classification has been enormously important promoting research and clinical management of patients with headache. It is a living document that develops from edition to edition and changes have been increasingly based on research, so called classification research. The aim of the present review is to present recent results of such research and to characterize the methods available for it.MethodsPublished research was identified by systematic search of PubMed. Lists of references of identified articles and the table of content of the last five years of Cephalalgia were screened.ResultsThe major results of identified articles are summarized. Thereafter the different methodologies applied in these studies are described. Finally, some suggestions are made for the future consideration of the fourth classification committee.ConclusionClassification research is emerging as an important avenue of headache research. It has a multitude of different designs available and many of them do not need advanced equipment.
{"title":"Research to improve headache classification: Results, methods, and future challenges.","authors":"Jes Olesen","doi":"10.1177/03331024251377753","DOIUrl":"https://doi.org/10.1177/03331024251377753","url":null,"abstract":"<p><p>IntroductionThe international headache classification has been enormously important promoting research and clinical management of patients with headache. It is a living document that develops from edition to edition and changes have been increasingly based on research, so called classification research. The aim of the present review is to present recent results of such research and to characterize the methods available for it.MethodsPublished research was identified by systematic search of PubMed. Lists of references of identified articles and the table of content of the last five years of <i>Cephalalgia</i> were screened.ResultsThe major results of identified articles are summarized. Thereafter the different methodologies applied in these studies are described. Finally, some suggestions are made for the future consideration of the fourth classification committee.ConclusionClassification research is emerging as an important avenue of headache research. It has a multitude of different designs available and many of them do not need advanced equipment.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 10","pages":"3331024251377753"},"PeriodicalIF":4.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249947","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}
Pub Date : 2025-10-01Epub Date: 2025-10-27DOI: 10.1177/03331024251391751
Jack Botros, Abby I Metzler, David P Darrow, Crina M Peterson, Monique M Montenegro, Donald R Nixdorf
{"title":"Toward ICHD-4: Aligning ICHD and ICOP criteria for trigeminal autonomic cephalalgias and migraine.","authors":"Jack Botros, Abby I Metzler, David P Darrow, Crina M Peterson, Monique M Montenegro, Donald R Nixdorf","doi":"10.1177/03331024251391751","DOIUrl":"https://doi.org/10.1177/03331024251391751","url":null,"abstract":"","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 10","pages":"3331024251391751"},"PeriodicalIF":4.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145376614","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}
Pub Date : 2025-10-01Epub Date: 2025-10-24DOI: 10.1177/03331024251387449
Tayla A Rees, Diana Doukhi, Victor S Wang, Anita Balcerbula, Michelle Bravo, Haniyeh Fathi, Bahtigul Holmuratova, Michalis Kodounis, Seblewongel A Seyoum, Semih Tasdelen, Hasmik Vekilyan, Edoardo Caronna, Patricia Pozo-Rosich
BackgroundNeck pain is common in migraine patients, occurring during all migraine phases and between attacks. It can be a migraine symptom, trigger or a coexisting condition, and is associated with greater disability and poorer treatment response. There is evidence that neck pain associated with headaches can be frequently incorrectly diagnosed as a cervical disorder rather than migraine, resulting in a lack of appropriate treatment. Accurately assessing the connection between neck pain and migraine is crucial for effective treatment.MethodsThis narrative review aims to summarise existing research on the role and contribution of neck pain in migraine, both as a symptom and a trigger, and outlines future research needed to deepen our understanding of this relationship. It also proposes a structured approach for assessing neck pain in migraine and a treatment algorithm, offering guidance for clinical evaluation and treatment. For this purpose, a comprehensive narrative review was conducted using PubMed, covering preclinical, clinical, neurophysiological and imaging evidence on migraine and neck pain.ResultsMigraine patients frequently exhibit cervical dysfunction, tenderness and altered posture, with overlapping neuroanatomical pathways of the neck and trigeminal systems, suggesting shared mechanisms of nociception and migraine initiation. Clinical assessment involves a thorough history, physical exam and exclusion of secondary causes. Standard migraine therapies, such as amitriptyline and onabotulinumtoxinA, may help reduce neck pain and non-pharmacological treatments, such as physical therapy, acupuncture and behavioural strategies, show some promise. However, evidence on neck pain relief is limited.ConclusionsAccurately distinguishing whether neck pain is a symptom, trigger or comorbid condition in migraine is essential for guiding effective treatment strategies. Both pharmacological and non-pharmacological approaches may help manage migraine-associated neck pain. However, few studies have assessed the effects of acute or preventive migraine therapies, particularly calcitonin gene-related peptide-targeted treatments, on neck pain, highlighting a significant gap in our current knowledge. Future research should evaluate the effectiveness of these therapies on neck pain, both alone and in combination with non-pharmacological interventions.
{"title":"Neck pain in migraine: A narrative review and steps to correct evaluation and treatment.","authors":"Tayla A Rees, Diana Doukhi, Victor S Wang, Anita Balcerbula, Michelle Bravo, Haniyeh Fathi, Bahtigul Holmuratova, Michalis Kodounis, Seblewongel A Seyoum, Semih Tasdelen, Hasmik Vekilyan, Edoardo Caronna, Patricia Pozo-Rosich","doi":"10.1177/03331024251387449","DOIUrl":"https://doi.org/10.1177/03331024251387449","url":null,"abstract":"<p><p>BackgroundNeck pain is common in migraine patients, occurring during all migraine phases and between attacks. It can be a migraine symptom, trigger or a coexisting condition, and is associated with greater disability and poorer treatment response. There is evidence that neck pain associated with headaches can be frequently incorrectly diagnosed as a cervical disorder rather than migraine, resulting in a lack of appropriate treatment. Accurately assessing the connection between neck pain and migraine is crucial for effective treatment.MethodsThis narrative review aims to summarise existing research on the role and contribution of neck pain in migraine, both as a symptom and a trigger, and outlines future research needed to deepen our understanding of this relationship. It also proposes a structured approach for assessing neck pain in migraine and a treatment algorithm, offering guidance for clinical evaluation and treatment. For this purpose, a comprehensive narrative review was conducted using PubMed, covering preclinical, clinical, neurophysiological and imaging evidence on migraine and neck pain.ResultsMigraine patients frequently exhibit cervical dysfunction, tenderness and altered posture, with overlapping neuroanatomical pathways of the neck and trigeminal systems, suggesting shared mechanisms of nociception and migraine initiation. Clinical assessment involves a thorough history, physical exam and exclusion of secondary causes. Standard migraine therapies, such as amitriptyline and onabotulinumtoxinA, may help reduce neck pain and non-pharmacological treatments, such as physical therapy, acupuncture and behavioural strategies, show some promise. However, evidence on neck pain relief is limited.ConclusionsAccurately distinguishing whether neck pain is a symptom, trigger or comorbid condition in migraine is essential for guiding effective treatment strategies. Both pharmacological and non-pharmacological approaches may help manage migraine-associated neck pain. However, few studies have assessed the effects of acute or preventive migraine therapies, particularly calcitonin gene-related peptide-targeted treatments, on neck pain, highlighting a significant gap in our current knowledge. Future research should evaluate the effectiveness of these therapies on neck pain, both alone and in combination with non-pharmacological interventions.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 10","pages":"3331024251387449"},"PeriodicalIF":4.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145367869","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}
Pub Date : 2025-10-01Epub Date: 2025-10-17DOI: 10.1177/03331024251385965
Manjit Singh Matharu, Stephen Silberstein, Hsiangkuo Yuan, Deborah Edgar, Roos Colman, Todd J Schwedt, Michel Lanteri-Minet, Mark Obermann
<p><p>BackgroundThis systematic review and meta-analysis synthesized migraine-related disability outcomes according to headache frequency subclassifications, including low-frequency episodic migraine (LFEM), high-frequency episodic migraine (HFEM) and chronic migraine (CM).MethodsWe searched the PubMed and Cochrane Library (CENTRAL) up to 16 October 2024 for peer-reviewed non-interventional studies reporting migraine-related disability outcomes in CM and subclassifications of episodic migraine (e.g. LFEM and HFEM). Eligible studies with an HFEM subgroup were grouped by headache frequency measure (monthly migraine days [MMD] or monthly headache days [MHD]), HFEM subgroup, disability parameter and study setting. Random-effects meta-analyses were conducted on groups with three or more studies, with the results presented in forest plots. Risk of bias was assessed using Joanna Briggs Institute tools.ResultsOf the 32 included studies, 27 were grouped, yielding five meta-analysis groups containing three or more studies. All five groups had an HFEM subgroup of 8-14 MHD. Accordingly, we classified LFEM as 0-7 MHD and CM as ≥15 MHD. Ten studies contributed data to the five meta-analysis groups. Estimated pooled values are reported by headache frequency subgroup for each meta-analysis group: LFEM (95% confidence interval [CI]), HFEM (95% CI) and CM (95% CI). For meta-analysis group 1, four population-based studies reported Migraine Disability Assessment (MIDAS) Grade IV proportions, with pooled values of 11.1% (7.1-17.1), 43.9% (31.8-56.9) and 57.5% (42.7-71.1), respectively. For meta-analysis group 2, five population-based studies documented Work Productivity and Activity Impairment (WPAI) outcomes. Pooled mean overall work productivity impairment (OWPI) scores were 36.9% (30.8-43.1), 44.7% (38.4-51.0) and 52.0% (47.7-56.3), respectively. Pooled mean activity impairment (AI) scores were 36.4% (33.7-39.1), 46.4% (42.8-50.0) and 53.5% (52.1-54.8), respectively. For meta-analysis group 3, three clinic-based studies presented MIDAS Grade IV proportions. Pooled values were 15.0% (4.4-40.5), 42.4% (17.1-72.4) and 65.7% (30.3-89.4), respectively. For meta-analysis group 4, three clinic-based studies reported WPAI outcomes. Pooled mean OWPI scores were 28.8% (21.6-35.9), 40.2% (36.2-44.2) and 49.6% (46.3-52.9), respectively. Pooled mean AI scores were 29.4% (21.9-36.9), 43.5% (39.0-48.1) and 51.6% (48.8-54.4), respectively. For meta-analysis group 5, three clinic-based studies detailed MIDAS scores. Pooled mean scores were 10.7 (3.9-17.5), 23.9 (9.4-38.4) and 49.6 (15.8-83.3), respectively.ConclusionsThis study showed a pattern of increasing migraine-related disability with rising headache frequency. Regardless of study setting, our meta-analyses also suggested a severe level of disability in many individuals (42%-44%) with HFEM, highlighting an unmet need for more effective migraine management. Disability burden and headache frequency should both be considered wh
{"title":"Migraine-related disability according to headache frequency subclassifications: A systematic review and meta-analysis.","authors":"Manjit Singh Matharu, Stephen Silberstein, Hsiangkuo Yuan, Deborah Edgar, Roos Colman, Todd J Schwedt, Michel Lanteri-Minet, Mark Obermann","doi":"10.1177/03331024251385965","DOIUrl":"10.1177/03331024251385965","url":null,"abstract":"<p><p>BackgroundThis systematic review and meta-analysis synthesized migraine-related disability outcomes according to headache frequency subclassifications, including low-frequency episodic migraine (LFEM), high-frequency episodic migraine (HFEM) and chronic migraine (CM).MethodsWe searched the PubMed and Cochrane Library (CENTRAL) up to 16 October 2024 for peer-reviewed non-interventional studies reporting migraine-related disability outcomes in CM and subclassifications of episodic migraine (e.g. LFEM and HFEM). Eligible studies with an HFEM subgroup were grouped by headache frequency measure (monthly migraine days [MMD] or monthly headache days [MHD]), HFEM subgroup, disability parameter and study setting. Random-effects meta-analyses were conducted on groups with three or more studies, with the results presented in forest plots. Risk of bias was assessed using Joanna Briggs Institute tools.ResultsOf the 32 included studies, 27 were grouped, yielding five meta-analysis groups containing three or more studies. All five groups had an HFEM subgroup of 8-14 MHD. Accordingly, we classified LFEM as 0-7 MHD and CM as ≥15 MHD. Ten studies contributed data to the five meta-analysis groups. Estimated pooled values are reported by headache frequency subgroup for each meta-analysis group: LFEM (95% confidence interval [CI]), HFEM (95% CI) and CM (95% CI). For meta-analysis group 1, four population-based studies reported Migraine Disability Assessment (MIDAS) Grade IV proportions, with pooled values of 11.1% (7.1-17.1), 43.9% (31.8-56.9) and 57.5% (42.7-71.1), respectively. For meta-analysis group 2, five population-based studies documented Work Productivity and Activity Impairment (WPAI) outcomes. Pooled mean overall work productivity impairment (OWPI) scores were 36.9% (30.8-43.1), 44.7% (38.4-51.0) and 52.0% (47.7-56.3), respectively. Pooled mean activity impairment (AI) scores were 36.4% (33.7-39.1), 46.4% (42.8-50.0) and 53.5% (52.1-54.8), respectively. For meta-analysis group 3, three clinic-based studies presented MIDAS Grade IV proportions. Pooled values were 15.0% (4.4-40.5), 42.4% (17.1-72.4) and 65.7% (30.3-89.4), respectively. For meta-analysis group 4, three clinic-based studies reported WPAI outcomes. Pooled mean OWPI scores were 28.8% (21.6-35.9), 40.2% (36.2-44.2) and 49.6% (46.3-52.9), respectively. Pooled mean AI scores were 29.4% (21.9-36.9), 43.5% (39.0-48.1) and 51.6% (48.8-54.4), respectively. For meta-analysis group 5, three clinic-based studies detailed MIDAS scores. Pooled mean scores were 10.7 (3.9-17.5), 23.9 (9.4-38.4) and 49.6 (15.8-83.3), respectively.ConclusionsThis study showed a pattern of increasing migraine-related disability with rising headache frequency. Regardless of study setting, our meta-analyses also suggested a severe level of disability in many individuals (42%-44%) with HFEM, highlighting an unmet need for more effective migraine management. Disability burden and headache frequency should both be considered wh","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 10","pages":"3331024251385965"},"PeriodicalIF":4.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311905","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}
Pub Date : 2025-10-01Epub Date: 2025-10-09DOI: 10.1177/03331024251371686
Mingjie Zhang, Aihong Guo, Jin Wu, Hebo Wang, Yongbo Zhang, Hongjuan Dong, Jianguang Liu, Bei Zhang, Huailian Guo, Tingmin Yu, Zhihong Lu, Liheng Ma, Robert J Fountaine, Glenn C Pixton, Qi Zhong, Xiaoran Han, Shengyuan Yu
BackgroundThis study evaluated the long-term safety, tolerability and effectiveness of rimegepant, 75 mg orally disintegrating tablet, for the acute treatment of migraine in Chinese adults.MethodsThis phase 3, multicenter, open-label, single-arm study enrolled Chinese adults with a ≥1 year history of migraine (with or without aura), 6-18 moderate-to-severe migraine attacks/month within three months before a screening visit and at least six migraine days during a 30-day observation phase (OP). After the OP, eligible participants took rimegepant as needed (maximum one tablet per day) at the onset of mild-to-severe migraine attack for a long-term treatment (LTT) of 52 weeks.ResultsOverall, 240 participants were treated and 208 (86.3%) completed the study. During LTT, 203 (84.6%) participants reported ≥1 treatment-emergent adverse event (TEAE) and 46 (19.2%) reported ≥1 TEAE considered to be rimegepant-related. There were no rimegepant-related serious AEs or rimegepant-related TEAEs that led to treatment interruption or discontinuation. Mean reduction from the OP in monthly migraine days was observed as early as the first four weeks (-1.7; 95% confidence interval = -2.2 to -1.2), with an overall mean reduction of -4.4 (95% confidence interval = -4.9 to -3.9) days across LTT.ConclusionsRimegepant had a favorable long-term safety profile, was well tolerated in Chinese participants, and a reduction in the number of monthly migraine days was observed during the LLT.Trial registration: ClinicalTrials.gov identifier: NCT05371652.
{"title":"Rimegepant for the acute treatment of migraine: A phase 3, multicenter, open-label, long-term safety and effectiveness study in adults from China.","authors":"Mingjie Zhang, Aihong Guo, Jin Wu, Hebo Wang, Yongbo Zhang, Hongjuan Dong, Jianguang Liu, Bei Zhang, Huailian Guo, Tingmin Yu, Zhihong Lu, Liheng Ma, Robert J Fountaine, Glenn C Pixton, Qi Zhong, Xiaoran Han, Shengyuan Yu","doi":"10.1177/03331024251371686","DOIUrl":"10.1177/03331024251371686","url":null,"abstract":"<p><p>BackgroundThis study evaluated the long-term safety, tolerability and effectiveness of rimegepant, 75 mg orally disintegrating tablet, for the acute treatment of migraine in Chinese adults.MethodsThis phase 3, multicenter, open-label, single-arm study enrolled Chinese adults with a ≥1 year history of migraine (with or without aura), 6-18 moderate-to-severe migraine attacks/month within three months before a screening visit and at least six migraine days during a 30-day observation phase (OP). After the OP, eligible participants took rimegepant as needed (maximum one tablet per day) at the onset of mild-to-severe migraine attack for a long-term treatment (LTT) of 52 weeks.ResultsOverall, 240 participants were treated and 208 (86.3%) completed the study. During LTT, 203 (84.6%) participants reported ≥1 treatment-emergent adverse event (TEAE) and 46 (19.2%) reported ≥1 TEAE considered to be rimegepant-related. There were no rimegepant-related serious AEs or rimegepant-related TEAEs that led to treatment interruption or discontinuation. Mean reduction from the OP in monthly migraine days was observed as early as the first four weeks (-1.7; 95% confidence interval = -2.2 to -1.2), with an overall mean reduction of -4.4 (95% confidence interval = -4.9 to -3.9) days across LTT.ConclusionsRimegepant had a favorable long-term safety profile, was well tolerated in Chinese participants, and a reduction in the number of monthly migraine days was observed during the LLT.<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT05371652.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 10","pages":"3331024251371686"},"PeriodicalIF":4.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257436","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}
Pub Date : 2025-10-01Epub Date: 2025-10-30DOI: 10.1177/03331024251391371
Todd J Schwedt, Stefan Evers, Amy A Gelfand, Richard B Lipton, Arne May, Patricia Pozo-Rosich, Jean Schoenen, Cristina Tassorelli, Gisela M Terwindt, Shuu-Jiun Wang, Peter J Goadsby
{"title":"International Classification of Headache Disorders 4: Classification committee comments on differentiating primary from secondary headache and recognizing \"medication overuse\".","authors":"Todd J Schwedt, Stefan Evers, Amy A Gelfand, Richard B Lipton, Arne May, Patricia Pozo-Rosich, Jean Schoenen, Cristina Tassorelli, Gisela M Terwindt, Shuu-Jiun Wang, Peter J Goadsby","doi":"10.1177/03331024251391371","DOIUrl":"https://doi.org/10.1177/03331024251391371","url":null,"abstract":"","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 10","pages":"3331024251391371"},"PeriodicalIF":4.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145408318","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}
Pub Date : 2025-10-01Epub Date: 2025-10-23DOI: 10.1177/03331024251386794
Fernanda Mariano Ribeiro da Luz, Alexandre Ottoni Kaup, Darciane Favero Baggio, Flavio Henrique de Rezende Costa, Juliana Geremias Chichorro
Aim: To investigate the effect of different cannabinoid compounds on the periorbital mechanical allodynia and photosensitivity in acute and chronic migraine models.
Methods: Female Wistar rats were treated systemically with different cannabinoid compounds (cannabidiol, CBD, 30 mg/kg; CBD and cannabigerol, CBD/CBG - 2:1; CBD and 0.3% tetrahydrocannabinol (CBD/THC); or CBD/CBG/THC) followed by injection of calcitonin-gene-related peptide (CGRP) or pituitary adenylate cyclase-activating polypeptide (PACAP) into the trigeminal ganglion to induced immediate periorbital mechanical allodynia and late photosensitivity. The effect of CBD and CBD/THC was also assessed on periorbital mechanical allodynia and photosensitivity in the chronic migraine model induced by repeated nitroglycerin (NTG) injections.
Results: Periorbital mechanical allodynia induced by CGRP was significantly reduced by CBD alone and combined with THC or CBG. CBD/THC was the most effective treatment in this condition since it presented the longer effect (up to three hours) and was the only treatment capable of reducing late photosensitivity associated with CGRP. All four compounds presented antinociceptive effect on acute migraine-like responses induced by PACAP, with CBD alone presenting the longer effect (from 30 minutes up to two hours). Except for CBD/CBG, all compounds also reduced (up to two hours) late photosensitivity associated with PACAP. In the chronic migraine model induced by NTG, CBD reduced periorbital mechanical allodynia on days 5, 7 and 11, while CBD/THC suppressed the development of periorbital allodynia up to day 13 and significantly reduced photosensitivity up to three hours.
Conclusion: Altogether, these results suggest that cannabinoid compounds may represent effective alternatives for the treatment of episodic and chronic migraine.
{"title":"Efficacy of different cannabinoid compounds on migraine-like responses in female rats.","authors":"Fernanda Mariano Ribeiro da Luz, Alexandre Ottoni Kaup, Darciane Favero Baggio, Flavio Henrique de Rezende Costa, Juliana Geremias Chichorro","doi":"10.1177/03331024251386794","DOIUrl":"https://doi.org/10.1177/03331024251386794","url":null,"abstract":"<p><strong>Aim: </strong>To investigate the effect of different cannabinoid compounds on the periorbital mechanical allodynia and photosensitivity in acute and chronic migraine models.</p><p><strong>Methods: </strong>Female Wistar rats were treated systemically with different cannabinoid compounds (cannabidiol, CBD, 30 mg/kg; CBD and cannabigerol, CBD/CBG - 2:1; CBD and 0.3% tetrahydrocannabinol (CBD/THC); or CBD/CBG/THC) followed by injection of calcitonin-gene-related peptide (CGRP) or pituitary adenylate cyclase-activating polypeptide (PACAP) into the trigeminal ganglion to induced immediate periorbital mechanical allodynia and late photosensitivity. The effect of CBD and CBD/THC was also assessed on periorbital mechanical allodynia and photosensitivity in the chronic migraine model induced by repeated nitroglycerin (NTG) injections.</p><p><strong>Results: </strong>Periorbital mechanical allodynia induced by CGRP was significantly reduced by CBD alone and combined with THC or CBG. CBD/THC was the most effective treatment in this condition since it presented the longer effect (up to three hours) and was the only treatment capable of reducing late photosensitivity associated with CGRP. All four compounds presented antinociceptive effect on acute migraine-like responses induced by PACAP, with CBD alone presenting the longer effect (from 30 minutes up to two hours). Except for CBD/CBG, all compounds also reduced (up to two hours) late photosensitivity associated with PACAP. In the chronic migraine model induced by NTG, CBD reduced periorbital mechanical allodynia on days 5, 7 and 11, while CBD/THC suppressed the development of periorbital allodynia up to day 13 and significantly reduced photosensitivity up to three hours.</p><p><strong>Conclusion: </strong>Altogether, these results suggest that cannabinoid compounds may represent effective alternatives for the treatment of episodic and chronic migraine.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 10","pages":"3331024251386794"},"PeriodicalIF":4.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354073","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}
Pub Date : 2025-10-01Epub Date: 2025-10-24DOI: 10.1177/03331024251387721
Patricia Pozo-Rosich, Edoardo Caronna, Simona Sacco, Mario F P Peres, Sait Ashina, Aynur Özge, Fayyaz Ahmed, Maria Karina Velez-Jimenez, Bronwyn Jenkins, Shuu-Jiun Wang, Todd J Schwedt, Fumihiko Sakai, Morris Levin, Rami Burstein, Gisela M Terwindt, Cristina Tassorelli
Migraine is one of the most disabling diseases worldwide, especially when it transforms into chronic migraine, which is often associated with medication overuse and can become resistant or even refractory to treatments. Molecular, neuroimaging and neurophysiological changes have been described in chronic migraine, some of which might not be fully reversible with preventive treatment. For these reasons, we should aim to prevent this transition, and initiate preventive treatment before disease becomes refractory and burden increases. Preventive migraine treatments are often delayed because of access to care, stigma leading to undertreatment and patients' reluctance as a result of fear of side effects and, in some cases, fear of being labeled as chronically ill. With the availability of effective and well-tolerated preventive treatments, we must shift our mindset and take advantage of new opportunities to initiate preventive treatment earlier. In this International Headache Society position statement, we propose a migraine preventive strategy under the idea of shifting from reactive treatment once disability is established (prevention of attacks), to proactive, individualized prevention initiated early with safe, effective and tolerable therapies (prevention of disease progression). This approach is based on 1) promoting the early initiation of effective and tolerable preventive therapies, starting from two to four monthly migraine days in line with the majority of current guidelines and recommendations and 2) fostering longitudinal studies to gather more evidence on the potential benefit of early prevention, with the final goal of improving patient outcomes, promoting excellent migraine care, enhancing individual and social well-being, and, ultimately, preventing migraine progression and preserving brain health.
{"title":"Early treatment in migraine - A call to shift prevention from attacks to disease progression: A position statement from the International Headache Society.","authors":"Patricia Pozo-Rosich, Edoardo Caronna, Simona Sacco, Mario F P Peres, Sait Ashina, Aynur Özge, Fayyaz Ahmed, Maria Karina Velez-Jimenez, Bronwyn Jenkins, Shuu-Jiun Wang, Todd J Schwedt, Fumihiko Sakai, Morris Levin, Rami Burstein, Gisela M Terwindt, Cristina Tassorelli","doi":"10.1177/03331024251387721","DOIUrl":"10.1177/03331024251387721","url":null,"abstract":"<p><p>Migraine is one of the most disabling diseases worldwide, especially when it transforms into chronic migraine, which is often associated with medication overuse and can become resistant or even refractory to treatments. Molecular, neuroimaging and neurophysiological changes have been described in chronic migraine, some of which might not be fully reversible with preventive treatment. For these reasons, we should aim to prevent this transition, and initiate preventive treatment before disease becomes refractory and burden increases. Preventive migraine treatments are often delayed because of access to care, stigma leading to undertreatment and patients' reluctance as a result of fear of side effects and, in some cases, fear of being labeled as chronically ill. With the availability of effective and well-tolerated preventive treatments, we must shift our mindset and take advantage of new opportunities to initiate preventive treatment earlier. In this International Headache Society position statement, we propose a migraine preventive strategy under the idea of shifting from reactive treatment once disability is established (prevention of attacks), to proactive, individualized prevention initiated early with safe, effective and tolerable therapies (prevention of disease progression). This approach is based on 1) promoting the early initiation of effective and tolerable preventive therapies, starting from two to four monthly migraine days in line with the majority of current guidelines and recommendations and 2) fostering longitudinal studies to gather more evidence on the potential benefit of early prevention, with the final goal of improving patient outcomes, promoting excellent migraine care, enhancing individual and social well-being, and, ultimately, preventing migraine progression and preserving brain health.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 10","pages":"3331024251387721"},"PeriodicalIF":4.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145367780","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}
Pub Date : 2025-10-01Epub Date: 2025-10-21DOI: 10.1177/03331024251388094
Caylee R McCain, Michael H Parrish, Petr Melikov, Wayne D Rosamond, Sweta Sengupta, Frank Spinale, Tushar Trivedi, Stefanie Wood, Souvik Sen
AimMigraine with aura is a risk factor for ischemic stroke. To further assess this risk factor in relation to ischemic stroke, along with other risk factors, we created the migraine associated risk of stroke score (MARS+), making it applicable to migraineurs. The risk score includes vascular risk factors, migraine characteristics and medications used in migraine patients.MethodsWe prospectively evaluated participants in Atherosclerosis Risk in Communities Cohort (ARIC) with a history of migraine. In this population, we tested the association of potential risk factors for ischemic stroke using a Cox proportional hazards model. The coefficient of each variable was divided by the lowest β value and rounded to the nearest integer. The sum of the weighted score of the reported risk factors was found and categorized into two prognostic groups.ResultsWe assessed migraine characteristics (aura, migraine frequency and duration) and medications that were in current use by participants, mean ± SD age 58 ± 5.5 years, 86% white, 14% black and 77% women (ergot alkaloids, triptans, hormone replacement therapy, sympathomimetics, steroids, selective serotonin reuptake inhibitors and opioids), in addition to traditional risk factors. Based on the points derived from the significant factors we assigned age ≥65 years = 1, non-white race = 2, hypertension = 2, diabetes = 3, body mass index ≥30 = 2, atrial fibrillation = 2, use of steroid medications = 3, use of selective serotonin reuptake inhibitor medications = 1, opioids = 2, presence of aura = 2 and duration <5 years = 1 to total 21 points. A cut-off of MARS+ ≥5 was considered as a lifetime high risk for ischemic stroke based on receiver operating characteristic curve and Youden's index. Of the 1485 participants with migraine, 112 had an ischemic stroke. MARS+ ≥5 revealed a hazard ratio of 4.09 (95% confidence interval = 2.67-6.26).ConclusionsThe MARS+ score is used to predict ischemic stroke in middle-aged migraine sufferers. This risk score, in addition to generalizability, includes factors such as migraine characteristics and medications that may increase stroke risk.
{"title":"Introducing a risk score for predicting ischemic stroke in migraine with or without visual aura.","authors":"Caylee R McCain, Michael H Parrish, Petr Melikov, Wayne D Rosamond, Sweta Sengupta, Frank Spinale, Tushar Trivedi, Stefanie Wood, Souvik Sen","doi":"10.1177/03331024251388094","DOIUrl":"https://doi.org/10.1177/03331024251388094","url":null,"abstract":"<p><p>AimMigraine with aura is a risk factor for ischemic stroke. To further assess this risk factor in relation to ischemic stroke, along with other risk factors, we created the migraine associated risk of stroke score (MARS+), making it applicable to migraineurs. The risk score includes vascular risk factors, migraine characteristics and medications used in migraine patients.MethodsWe prospectively evaluated participants in Atherosclerosis Risk in Communities Cohort (ARIC) with a history of migraine. In this population, we tested the association of potential risk factors for ischemic stroke using a Cox proportional hazards model. The coefficient of each variable was divided by the lowest β value and rounded to the nearest integer. The sum of the weighted score of the reported risk factors was found and categorized into two prognostic groups.ResultsWe assessed migraine characteristics (aura, migraine frequency and duration) and medications that were in current use by participants, mean ± SD age 58 ± 5.5 years, 86% white, 14% black and 77% women (ergot alkaloids, triptans, hormone replacement therapy, sympathomimetics, steroids, selective serotonin reuptake inhibitors and opioids), in addition to traditional risk factors. Based on the points derived from the significant factors we assigned age ≥65 years = 1, non-white race = 2, hypertension = 2, diabetes = 3, body mass index ≥30 = 2, atrial fibrillation = 2, use of steroid medications = 3, use of selective serotonin reuptake inhibitor medications = 1, opioids = 2, presence of aura = 2 and duration <5 years = 1 to total 21 points. A cut-off of MARS+ ≥5 was considered as a lifetime high risk for ischemic stroke based on receiver operating characteristic curve and Youden's index. Of the 1485 participants with migraine, 112 had an ischemic stroke. MARS+ ≥5 revealed a hazard ratio of 4.09 (95% confidence interval = 2.67-6.26).ConclusionsThe MARS+ score is used to predict ischemic stroke in middle-aged migraine sufferers. This risk score, in addition to generalizability, includes factors such as migraine characteristics and medications that may increase stroke risk.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 10","pages":"3331024251388094"},"PeriodicalIF":4.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336543","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}