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The Journal of Headache and Pain Sep 2023Although the involvement of calcitonin gene-related peptide (CGRP) in migraines is well-established, its specific role in investigating the aura phase, which often...
BACKGROUND
Although the involvement of calcitonin gene-related peptide (CGRP) in migraines is well-established, its specific role in investigating the aura phase, which often precedes the headache, remains largely unexplored. This study aims to instigate CGRP's potential in triggering aura, thus establishing its role in the early stages of migraine.
METHODS
In this open-label, non-randomized, single-arm trial, 34 participants with migraine with aura received continuous intravenous infusion of CGRP (1.5 µg/min) over 20 min on a single experimental day. Participants were required to be free of headache and report no use of acute medications 24 h before infusion start. The primary endpoint was the incidence of migraine aura during the 12-hour observational period after the start of infusion.
RESULTS
Thirteen (38%) of 34 participants developed migraine aura after CGRP infusion. In addition, 24 (71%) of 34 participants developed migraine headache following CGRP infusion.
CONCLUSIONS
Our findings suggest that CGRP could play an important role in the early phases of a migraine attack, including during the aura phase. These insights offer a new perspective on the pathogenesis of migraines with aura. They underscore the need for additional research to further explore the role of CGRP in these initial stages of a migraine attack, and potentially inform future development of therapeutic interventions.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04592952.
Topics: Humans; Calcitonin Gene-Related Peptide; Migraine with Aura; Migraine Disorders; Headache; Epilepsy
PubMed: 37679723
DOI: 10.1186/s10194-023-01656-4 -
The Journal of Headache and Pain Apr 2024Sexual dimorphism has been revealed for many neurological disorders including chronic pain. Prelicinal studies and post-mortem analyses from male and female human donors... (Review)
Review
Sexual dimorphism has been revealed for many neurological disorders including chronic pain. Prelicinal studies and post-mortem analyses from male and female human donors reveal sexual dimorphism of nociceptors at transcript, protein and functional levels suggesting different mechanisms that may promote pain in men and women. Migraine is a common female-prevalent neurological disorder that is characterized by painful and debilitating headache. Prolactin is a neurohormone that circulates at higher levels in females and that has been implicated clinically in migraine. Prolactin sensitizes sensory neurons from female mice, non-human primates and humans revealing a female-selective pain mechanism that is conserved evolutionarily and likely translationally relevant. Prolactin produces female-selective migraine-like pain behaviors in rodents and enhances the release of calcitonin gene-related peptide (CGRP), a neurotransmitter that is causal in promoting migraine in many patients. CGRP, like prolactin, produces female-selective migraine-like pain behaviors. Consistent with these observations, publicly available clinical data indicate that small molecule CGRP-receptor antagonists are preferentially effective in treatment of acute migraine therapy in women. Collectively, these observations support the conclusion of qualitative sex differences promoting migraine pain providing the opportunity to tailor therapies based on patient sex for improved outcomes. Additionally, patient sex should be considered in design of clinical trials for migraine as well as for pain and reassessment of past trials may be warranted.
Topics: Migraine Disorders; Humans; Female; Animals; Sex Characteristics; Calcitonin Gene-Related Peptide; Prolactin; Male
PubMed: 38658853
DOI: 10.1186/s10194-024-01771-w -
Medicina (Kaunas, Lithuania) Jun 2022Background and Objectives: Migraines are one of the most common types of primary headaches in neurology. Many studies to date have investigated cognitive impairment in...
Background and Objectives: Migraines are one of the most common types of primary headaches in neurology. Many studies to date have investigated cognitive impairment in migraineurs, but the results are inconsistent. This study aimed to investigate the cognitive function of migraineurs and explore the influencing factors. Material and Methods: A total of 117 patients with primary headaches (87 with migraine and 30 with tension-type headache (TTH)) and 30 healthy controls were enrolled. General information and data on headache clinical characteristics, and assessments of headache-related disability, psychological symptoms, and cognitive function were collected for statistical analysis. Results: The Montreal Cognitive Assessment (MoCA) total score and the scores of visuospatial and executive functions, language, and delayed recall in the migraine and TTH groups were significantly lower than those in the healthy control group (all p < 0.05). The MoCA total score did not correlate with Headache impact test-6, Migraine Disability Assessment Questionnaire, Patient Health Questionnaire-9, or Generalized Anxiety Disorder Questionnaire-7 scores in migraineurs (all p > 0.0125). The multiple linear regression analysis showed that age and duration of attack had a major influence on the overall and various fields of cognition in migraineurs. Conclusion: The study confirmed the impairment of cognitive function in patients with migraine and TTH, and found that the duration of attack had an effect on cognitive function in migraineurs.
Topics: Cognitive Dysfunction; Headache; Humans; Migraine Disorders; Surveys and Questionnaires; Tension-Type Headache
PubMed: 35888589
DOI: 10.3390/medicina58070870 -
Psychiatria Polska Apr 2023Migraine and depression often coexist and constitute an important clinical problem. Both disorders are associated with the necessity of chronic treatment, and their... (Review)
Review
Migraine and depression often coexist and constitute an important clinical problem. Both disorders are associated with the necessity of chronic treatment, and their mutual coexistence contributes to the phenomenon of drug resistance. Influencing the functioning of patients, they also cause numerous social consequences - affecting the quality of life and achievement of personal goals of patients. This review presents factors that may explain the common pathomechanisms of depression and migraine. Structural and functional disturbances of the central nervous system (CNS), disturbances in the neurotransmitter systems, inflammatory theories, hormonal disturbances, as well as a possible genetic basis were taken into account. Due to the fact that both depression and migraine have a multifactorial etiology and at the present stage of scientific research it is difficult to clearly determine which factor is the most important, such a broad overview has been presented. It is also difficult to determine which of the above-mentioned factors, well documented in international studies, only coexist, and which of them may have a cause-and-effect relationship in the described disorders. Further research into the comorbidity and causes of migraine and depression seems to be worth considering.
Topics: Humans; Depression; Quality of Life; Migraine Disorders; Comorbidity
PubMed: 36371736
DOI: 10.12740/PP/OnlineFirst/143982 -
Annals of the Academy of Medicine,... Apr 2020Migraine is one of top 5 medical conditions that contribute to Years Lived with Disability and affects approximately 1 billion people from around the world. To date,... (Review)
Review
Migraine is one of top 5 medical conditions that contribute to Years Lived with Disability and affects approximately 1 billion people from around the world. To date, preventive treatment and acute therapies for migraine are limited, have undesirable side effects and are poorly tolerated in patients. In the last few decades, considerable advances in our understanding of migraine and its pathophysiology have paved the way for the development of targeted treatment options. Calcitonin gene-related peptide (CGRP) plays an integral role in the neurobiology of migraine, and new classes of drugs that target the CGRP pathway have included gepants and CGRP pathway monoclonal antibodies. Serotonin 5-HT receptor agonists-namely ditans-have also been developed to treat acute migraine. Lastly, non-invasive neuromodulation offers another treatment option for migraine patients who prefer treatments that have fewer side effects and are well tolerated. In this review, we discussed emerging treatment options for migraine that were made available in recent years.
Topics: Humans; Migraine Disorders
PubMed: 32419007
DOI: No ID Found -
Neurology India 2021Migraine is a common neurological disorder with significant morbidity and disability. There is growing evidence that migraine is associated with cardiovascular diseases... (Review)
Review
BACKGROUND
Migraine is a common neurological disorder with significant morbidity and disability. There is growing evidence that migraine is associated with cardiovascular diseases and stroke.
OBJECTIVE
The aim of this study was to provide an update on the association of migraine with some common vascular diseases in persons suffering from the disease and discuss the clinical implications.
METHODS AND MATERIALS
We searched PUBMED database using the MeSH terms "Stroke", "Coronary Artery Disease", "Myocardial Ischemia", "Atrial Fibrillation", "White Matter" and "Dementia, Vascular", in combination with "Migraine Disorders", "Migraine with Aura" and "Migraine without Aura" and reviewed the relevant studies. We studied articles mostly in English for the past 10 years, without excluding older articles that were relevant to this review. We also searched the reference lists of articles obtained and included some insightful reviews on 'Migraine and Vascular Risk'.
RESULTS
The association between migraine and vascular diseases is strong and consistent for ischemic stroke and migraine with aura especially in young women, with oral contraceptive use and smoking. Although literature reports a higher prevalence of obesity, dyslipidemia, and family history of cardiovascular diseases in migraineurs, the 'migraine-vascular' connection persists in models where the traditional vascular risk factors are adjusted, implicating a migraine-specific pathophysiology at work. There is some evidence linking an adverse vascular risk factor profile to incident myocardial infarction in people with migraine. The association with hemorrhagic stroke is more variable.
CONCLUSION
Although the absolute effect of migraine on 'vascular risks' is small, good practice parameters dwell on treating and reducing existing cardiovascular risk factors through lifestyle modification, encouraging smoking cessation, and advocating the wise use of agents like ergot alkaloids and oral contraceptives, after a risk-benefit analysis.
Topics: Female; Humans; Migraine Disorders; Myocardial Infarction; Risk Factors; Smoking; Stroke
PubMed: 34003152
DOI: 10.4103/0028-3886.315974 -
Romanian Journal of Ophthalmology 2020Retinal migraine is usually defined by transitory attacks of fully reversible monocular visual loss, mostly with aura. An accurate diagnostic can be completed based upon... (Review)
Review
Retinal migraine is usually defined by transitory attacks of fully reversible monocular visual loss, mostly with aura. An accurate diagnostic can be completed based upon the International Classification of Headache Disorders-2 (ICHD-2) criteria. In view of this, we summarized some clinical features, treatment principles, complications, prognosis and prophylaxis.
Topics: Disease Management; Humans; Migraine Disorders; Prognosis; Retinal Diseases; Retinal Vessels; Vision, Monocular
PubMed: 32685773
DOI: No ID Found -
Scientific Reports Aug 2023Observational studies have yielded conflicting results regarding the relationship between tea intake and migraine risk. Residual confounders and potential reverse...
Observational studies have yielded conflicting results regarding the relationship between tea intake and migraine risk. Residual confounders and potential reverse causality are unavoidable in traditional observational studies. To provide evidence for establishing viable disease screening and prevention strategies, a Mendelian randomization study (MR) was conducted to determine the causal inference between tea intake and migraine. We obtained 28 single-nucleotide polymorphisms (SNPs) for any migraine (AM), 25 SNPs for migraine with aura (MA), and 27 SNPs for migraine without aura (MO) associated with tea intake derived from a large genome-wide association study (GWAS) of the UK Biobank (UKBB) (containing 447,485 samples). The largest migraine GWAS performed by the International Headache Genetics Consortium (IHGC), including 29,209 cases and 172,931 controls, provided data on migraines and their subtypes (MA and MO). We used the method of inverse variance weighting (IVW) with fixed effects as the first-string MR selection. Sensitivity analysis and MR-pleiotropy residual sum and outlier (MR-PRESSO) method further assessed the robustness of the findings. Based on the conclusion of IVW in the fixed effects model, we found that tea intake had no causal relationship with AM risk (odds ratio (OR), 0.94; 95% confidence interval (CI), 0.70-1.25; P = 0.65), MA risk (OR, 0.93; 95% CI, 0.51-1.72; P = 0.83), or MO risk (OR, 0.90; 95% CI, 0.52-1.54; P = 0.69). Sensitivity analyses and MR-PRESSO showed no directional pleiotropy or heterogeneity. Our two-sample MR investigation found no causality between tea intake and migraine risk in European populations, implying that attempts to change tea drinking habits may not lead to a reduced risk of migraine.
Topics: Humans; Genome-Wide Association Study; Mendelian Randomization Analysis; Migraine Disorders; Migraine with Aura; Tea
PubMed: 37558735
DOI: 10.1038/s41598-023-40171-z -
Eye (London, England) Aug 2023Visual snow syndrome is a neurological condition characterized by ongoing prominent phenomena described consistently as tiny dots moving across the entire visual field,... (Review)
Review
Visual snow syndrome is a neurological condition characterized by ongoing prominent phenomena described consistently as tiny dots moving across the entire visual field, often associated with complex visual symptoms. These can take the form of afterimages, entoptic phenomena, nyctalopia and light sensitivity. Although some of these symptoms can be benign, they can nonetheless become significantly impactful for many who experience them, particularly in cases that have a sudden and abrupt start. As visual snow syndrome becomes increasingly recognized in clinical practice we begin to learn about its typical presentation and underlying pathophysiology. Treatment of visual snow, however, still proves quite challenging, and efforts need to be focused on unravelling the biological mechanisms of the syndrome. This endeavour has characterized the most recent research on visual snow, mostly involving neuroimaging, neurophysiological and neurobehavioral studies aimed at understanding its underlying neural signature. Another important aspect of the syndrome, which will likely prove critical in deepening our understanding of visual snow, is represented by the intricate biological and historical connexion with migraine. This narrative review focused on visual snow syndrome will explore its clinical, pathophysiological and treatment aspects in detail.
Topics: Humans; Migraine Disorders; Vision Disorders; Visual Fields; Syndrome
PubMed: 36788360
DOI: 10.1038/s41433-023-02435-w -
The Journal of Headache and Pain Jul 2019Mouse models of rare monogenic forms of migraine provide a unique experimental system to study the cellular and circuit mechanisms of the primary brain dysfunctions... (Review)
Review
Mouse models of rare monogenic forms of migraine provide a unique experimental system to study the cellular and circuit mechanisms of the primary brain dysfunctions causing a migraine disorder. Here, we discuss the migraine-relevant phenotypes and the migraine-relevant functional alterations in the brain of five genetic mouse models of migraine, four of which carry mutations derived from patients with familial hemiplegic migraine (FHM) and the fifth carry a mutation from patients with both phenotypically normal MA and familial advanced sleep phase syndrome (FASPS). We focus on the latter mouse model, in which a ubiquitous serine-threonine kinase is mutated, and on two mouse models of pure FHM, in which a voltage-gated calcium channel controlling neurotransmitter release at most brain synapses and a Na/K ATPase that is expressed mainly in astrocytes in the adult brain are mutated, respectively. First, we describe the behavioral phenotypes of the genetic animal models and review the evidence that an increased susceptibility to experimentally induced cortical spreading depression (CSD) is a key migraine-relevant phenotype common to the five models. Second, we review the synaptic alterations in the cerebral cortex of the genetic models of migraine and discuss the mechanisms underlying their increased susceptibility to CSD. Third, we review the alterations in the trigeminovascular pain pathway and discuss possible implications for migraine pain mechanisms. Finally, we discuss the insights into migraine pathophysiology obtained from the genetic models of migraine, in particular regarding the mechanisms that make the brain of migraineurs susceptible to the ignition of "spontaneous" CSDs. Although the reviewed functional studies support the view of migraine as a disorder of the brain characterized by dysfunctional regulation of the excitatory/inhibitory balance in specific neuronal circuits, much work remains to be done in the genetic mouse models e.g. to identfy the relevant dysfunctional circuits and to establish whether and how the alterations in the function of specific circuits (in the cerebral cortex and/or other brain areas) are state-dependent and may, in certain conditions, favor CSD ignition and the migraine attack.
Topics: Animals; Cerebral Cortex; Disease Models, Animal; Humans; Mice; Migraine Disorders; Neurons
PubMed: 31299902
DOI: 10.1186/s10194-019-1029-5