Migraine and the trigeminovascular system—40 years and counting

Ashina, Messoud; Hansen, Jakob Møller; Phu, Thien; Melo‐Carrillo, Agustin; Burstein, Rami; Moskowitz, Michael A.

doi:10.1016/s1474-4422(19)30185-1

Cited by 379 publications

(312 citation statements)

References 91 publications

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“…Advances in therapies have made it possible to effectively prevent or reduce symptoms of migraine. Humanized monoclonal antibodies targeting CGRP and its receptor have recently been approved for migraine prophylaxis in adults [75,79,91,101,127,128]. Fremanezumab, a monoclonal antibody specific to CGRP, was approved by the FDA in September 2018 and by the EMA in March 2019 for migraine prevention in adults [76,90].…”

Section: Resultsmentioning

confidence: 99%

“…It is thought that monoclonal antibodies act peripherally because they do not cross the blood-brain barrier [79,87]. Possible sites of action for fremanezumab are the trigeminal ganglion and meningeal nociceptors [78,87,101]. A study in rats found that fremanezumab selectively inhibits activation of peripheral lightly myelinated Ad (but not unmyelinated C) meningeal neurons and central high-threshold (HT) [but not wide-dynamic-range (WDR)] trigeminovascular neurons by cortical spreading depression (CSD) in the meningeal sensory pathway [78,87].…”

Section: Cgrp As a Target: Mechanism Of Actionmentioning

confidence: 99%

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An Evidence-Based Review of Fremanezumab for the Treatment of Migraine

Urits

Clark

et al. 2020

Pain Ther

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Migraine headache is a common, chronic, debilitating disease with a complex etiology. Current therapy for migraine headache comprises either treatments targeting acute migraine pain or prophylactic therapy aimed at increasing the length of time between migraine episodes. Recent evidence suggests that calcium gene-related peptide (CGRP) is a critical component in the pathogenesis of migraines. Fremanezumab, a monoclonal antibody against CGRP, was recently approved by the Food and

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Section: Resultsmentioning

confidence: 99%

Section: Cgrp As a Target: Mechanism Of Actionmentioning

confidence: 99%

An Evidence-Based Review of Fremanezumab for the Treatment of Migraine

Urits

Clark

et al. 2020

Pain Ther

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“…The trigeminovascular system plays an integral role in migraine pathogenesis 11 . Within this framework, CGRP and various other neuropeptides are heavily involved in mediating certain aspects of the headache phase of migraine 12,13 .…”

Section: Cgrp and Migrainementioning

confidence: 99%

Dual Therapy With Anti‐CGRP Monoclonal Antibodies and Botulinum Toxin for Migraine Prevention: Is There a Rationale?

et al. 2020

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Objective.-To narratively review the pathophysiological rationale of dual therapy with anti-calcitonin gene-related peptide monoclonal antibodies and botulinum toxin type A in treatment-resistant chronic migraine prevention.Background.-For the prevention of chronic migraine, several pharmacological therapies are available, including oral medications, botulinum toxin type A, and the newly approved monoclonal antibodies targeting calcitonin gene-related peptide or its receptor. However, monotherapy does not yield benefits in some affected individuals, which raises the question of whether dual therapy with monoclonal antibodies and botulinum toxin type A hold promise in patients with treatment-resistant chronic migraine.Method.-We searched MEDLINE for articles published from database inception to December 31st, 2019. Publications were largely selected from the past 10 years but commonly referenced and highly regarded older publications were not excluded.Results.-Preclinical data suggest that anti-calcitonin gene-related peptide monoclonal antibodies and botulinum toxin type A have synergistic effects within the trigeminovascular system. Of note, findings indicate that fremanezumab -an antibody targeting the calcitonin gene-related peptide -mainly prevents the activation of Aδ-fibers, whereas botulinum toxin type A prevents the activation of C-fibers.Conclusion.-There is currently only indirect preclinical evidence to support a rationale for dual therapy with anti-calcitonin gene-related peptide monoclonal antibodies and botulinum toxin type A for chronic migraine prevention. Rigorous studies evaluating clinical efficacy, safety, and cost-effectiveness are needed. Abbreviations: BBB blood-brain barrier, BTX-A botulinum toxin typeA, CGRP calcitonin gene-related peptide, CM chronic migraine, CNS central nervous system, HT high-threshold, mAb monoclonal antibody, SNARE soluble N-ethylmaleimide-sensitive factor attachment protein receptor, TG trigeminal ganglion, TNC trigeminal nucleus caudalis, TRPA1 transient receptor potential ankyrin 1, TRPV1 transient receptor potential cation channel subfamily V member 1, WDR wide-dynamic range (

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“…There are potential pathophysiological overlaps with migraine and neuroendocrineimmune-related skin disorders, in which also calcitonin gene related peptide (CGRP) has been suggested to play a role. Moreover, the role of vascular changes in rosacea and migraine are not fully understood but remain an interesting hypothesis also when reflecting on genetic studies [21,38,39].…”

Section: Increased Comorbidity Based On Phenotypic Disease Networkmentioning

confidence: 99%

Burden of migraine in Finland: multimorbidity and phenotypic disease networks in occupational healthcare

Korolainen¹,

Tuominen²,

Kurki

et al. 2020

J Headache Pain

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Background: Migraine is a complex neurological disorder with high co-existing morbidity burden. The aim of our study was to examine the overall morbidity and phenotypic diseasome for migraine among people of working age using real world data collected as a part of routine clinical practice. Methods: Electronic medical records (EMR) of patients with migraine (n = 17,623) and age-and gender matched controls (n = 17,623) were included in this retrospective analysis. EMRs were assessed for the prevalence of ICD-10 codes, those with at least two significant phi correlations, and a prevalence >2.5% in migraine patients were included to phenotypic disease networks (PDN) for further analysis. An automatic subnetwork detection algorithm was applied in order to cluster the diagnoses within the PDNs. The diagnosis-wise connectivity based on the PDNs was compared between migraine patients and controls to assess differences in morbidity patterns. Results: The mean number of diagnoses per patient was increased 1.7-fold in migraine compared to controls. Altogether 1337 different ICD-10 codes were detected in EMRs of migraine patients. Monodiagnosis was present in 1% and 13%, and the median number of diagnoses was 12 and 6 in migraine patients and controls. The number of significant phi-correlations was 2.3-fold increased, and cluster analysis showed more clusters in those with migraine vs. controls (9 vs. 6). For migraine, the PDN was larger and denser and exhibited one large cluster containing fatigue, respiratory, sympathetic nervous system, gastrointestinal, infection, mental and mood disorder diagnoses. Migraine patients were more likely affected by multiple conditions compared to controls, even if no notable differences in morbidity patterns were identified through connectivity measures. Frequencies of ICD-10 codes on a three character and block level were increased across the whole diagnostic spectrum in migraine. Conclusions: Migraine was associated with an increased multimorbidity, evidenced by multiple different approaches in the study. A systematic increase in the morbidity across the whole spectrum of ICD-10 coded diagnoses, and when interpreting PDNs, were detected in migraine patients. However, no specific diagnoses explained the morbidity. The results reflect clinical praxis, but also undoubtedly, the pathophysiological phenotypes related to migraine, and emphasize the importance of better understanding migraine-related morbidity.

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Migraine and the trigeminovascular system—40 years and counting

Cited by 379 publications

References 91 publications

An Evidence-Based Review of Fremanezumab for the Treatment of Migraine

An Evidence-Based Review of Fremanezumab for the Treatment of Migraine

Dual Therapy With Anti‐CGRP Monoclonal Antibodies and Botulinum Toxin for Migraine Prevention: Is There a Rationale?

Burden of migraine in Finland: multimorbidity and phenotypic disease networks in occupational healthcare

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