Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Migraine with aura. Core disease mechanisms, molecular and cellular pathwa...

This report is retrieval-only and is generated directly from Asta results.

• Papers retrieved: 20
• Snippets retrieved: 20

Relevant Papers

[1] Molecular Mechanisms of Migraine: Nitric Oxide Synthase and Neuropeptides

• Authors: N. Karsan, Helin Gosalia, P. Goadsby
• Year: 2023
• Venue: International Journal of Molecular Sciences
• URL: https://www.semanticscholar.org/paper/54da53dc9a15ed3bc286d7c410df05133ebfac42
• DOI: 10.3390/ijms241511993
• PMID: 37569369
• PMCID: 10418996
• Citations: 32
• Summary: The identification that vasoconstriction is neither necessary nor required for headache abortion has changed the landscape of migraine treatment and has broadened the therapy targets for patients with vascular risk factors or vascular disease.
• Evidence snippets:
• Snippet 1 (score: 0.587) > Migraine is well recognised as being a neurovascular disorder, in which primarily neural dysfunction in areas such as the brainstem, hypothalamus, and basal ganglia structures [13], with subsequent secondary vascular involvement, causes the heterogeneous neurological phenotype [14]. The links between aura and headache biologically remain debated, as aura is thought to be a cortical phenomenon that typically occurs before or with headache [15], but can occur at any time in the migraine cycle [2,16], be prolonged [17] or persistent [18], and affects only 30% of those with migraine [19]. Indeed, it is more likely even for those with migraine with aura to experience headache attacks without aura associated [10]. Genetics have therefore contributed to the understanding of migraine mechanisms and possible drug targets, particularly in migraine with aura, but more common migraine is polygenic in nature. Much remains to be learned about how and if the same mechanisms are involved in migraine without aura, and what the associations between aura and headache are. > Additional understanding of the mechanisms of disease in migraine has come from an appreciation of the molecular biology of migraine. This has been recently contributed to by the increase in the development and use of experimental provocation models of human migraine [20]. The ability to use an exogenous compound to trigger phenotypically similar migraine-like attacks to spontaneous ones, to observe these and investigate treatment effects, as well as to conduct repeated measures imaging protocols during these attacks, have been important advances to the migraine research space. These human models have provided an opportunity to further develop an understanding of migraine molecular chemistry and, therefore, the development of drug targets.

[2] Reduction in retinal microvascular perfusion during migraine attacks

• Authors: Katherine Podraza, Nitin Bangera, Akira Féliz, Andrew C Charles
• Year: 2023
• Venue: Headache: The Journal of Head and Face Pain
• URL: https://www.semanticscholar.org/paper/17d4a0e2f22bcbbb899630c6fb71d4e52c593a03
• DOI: 10.1111/head.14654
• PMID: 38031892
• Citations: 5
• Influential citations: 1
• Summary: To determine if there are changes in structure and function of the retinal vasculature during and between migraine attacks using optical coherence tomography angiography (OCTA).
• Evidence snippets:
• Snippet 1 (score: 0.536) > 2][3] Although substantial progress has been made regarding basic mechanisms of migraine, many unanswered questions remain. 4One obstacle has been the absence of biomarkers that predict the phenotype of the disease, clinical course, or response to individual treatments. > Patients with migraine commonly experience pain in and around the eye, cranial autonomic symptoms including redness and tearing of the eye, and visual symptoms ranging from light sensitivity and visual blurring to dramatic visual phenomena occurring during the migraine aura.Little is known about what causes these visual symptoms.While some of the visual symptoms such as visual aura clearly originate in the visual cortex, it is also possible that the eye could play a role.Also, apart from any direct role in the symptoms of migraine, the retina may represent an accessible window onto more general vascular and nervous system mechanisms that are involved in migraine.Previously, changes in retinal layers and vascular structure have also been seen using optical coherence tomography (OCT) and/or OCT angiography (OCTA) in various neurological conditions including stroke, 5 multiple sclerosis, 6 Parkinson's disease, 7 and Alzheimer's disease. 8Migraine involves dysregulation of sensory processing and many of the same processes affecting the brain may involve the eye. 91][12] Additionally, similar vascular and autonomic nervous system pathways involved in migraine may affect the eye.8][19] Furthermore, the optic nerve represents a direct neural connection to the brain and changes in optic nerve structure and function occur in response to changes in intracranial pressure.Evaluation of these relationships during migraine attacks would be very informative. 20Finally, spreading depression, the slowly propagated wave of neural and glial activity whose occurrence in the occipital cortex is believed to underlie the migraine visual aura, 21,22 also occurs in the retina 23,24 and may be responsible for migraine with retinal aura. > Recent advances in optical imaging techniques have enabled visualization of the cells and blood vessels of the retina with high resolution at the capillary level.These techniques have been used in a small number of studies to investigate migraine.

[3] Mechanisms of migraine as a chronic evolutive condition

• Authors: A. Andreou, L. Edvinsson
• Year: 2019
• Venue: The Journal of Headache and Pain
• URL: https://www.semanticscholar.org/paper/483146e69822faff1ec8236b1c16d0ab6639f28d
• DOI: 10.1186/s10194-019-1066-0
• PMID: 31870279
• PMCID: 6929435
• Citations: 237
• Influential citations: 6
• Summary: Migraine is a life span neurological disorder that follows an evolutive age-dependent change in its prevalence and even clinical presentations, and genetic and epigenetic factors, inflammatory processes and central sensitization may play an important role.
• Evidence snippets:
• Snippet 1 (score: 0.520) > Migraine clinical and pathophysiological mechanisms are not static and evolve continuously. During lifespan the clinical phenotype of migraine changes. These changes may include transformation from episodic to chronic migraine or even a disappearance of some or all migraine symptoms all together. Genetic and epigenetic susceptibility may be responsible for such changes, although to date, studies failed to shed any light on how such genetic alterations may be responsible for migraine pathophysiology or any evolutive mechanism. On the other hand, anatomical changes in the brain of a migraine patient exist even from early childhood, but they do not seem to have any functional consequences. The causality dilemma of whether such changes are responsible for how migraine evolves, or whether migraine mechanisms drive these anatomic changes, remains to be answered. Even in its episodic form, migraine is an evolutive condition with different mechanisms involved in the evolutive process of a migraine attack. These mechanisms include hypothalamic alterations during the premonitory phase, cortical excitability in the aura phase, activation of the ascending trigeminothalamic pain pathway with an involvement of the peripheral trigeminal arm during the headache phase, and potential cortical changes during the postdrome phase. How migraine headache is triggered following hypothalamic activation remains unknown. A potential involvement of the parasympathetic pathway is possible, as it could be influenced by hypothalamic changes and in turn activate the trigeminal system through the trigemino-autonomic arc. Such a mechanisms could explain activation of the peripheral trigeminal system from a brain-initiated event. The mechanisms that underlie the development of chronic migraine from its episodic form are not well understood. Several factors have been identified to increase the risk for migraine chronification. Inflammation and central sensitization play a significant role in the evolutive mechanisms of chronic migraine. > The continuous changes in migraine phenotype and pathophysiology during a migraine attack between episodic and chronic migraine and during the patient lifespan, make migraine, even in its episodic form, a chronic evolutive disease. The APCs (article processing charges) for the articles

[4] Screening for Copy Number Variations of the 15q13.3 Hotspot in CHRNA7 Gene and Expression in Patients with Migraines

• Authors: Mehmet Fatih Özaltun, Sırma Geyik, Ş. Yılmaz
• Year: 2021
• Venue: Current Issues in Molecular Biology
• URL: https://www.semanticscholar.org/paper/a6299f065d1218ec59b37466186428168fcc2bc3
• DOI: 10.3390/cimb43020078
• PMID: 34563047
• PMCID: 8929100
• Citations: 5
• Summary: Downregulation of the CHRNA7 gene may contribute to the formation of migraine by inactivation of the alpha-7 nicotinic receptor (α7nAChR), which will lead to better understanding of the molecular mechanisms and pathogenesis.
• Evidence snippets:
• Snippet 1 (score: 0.519) > The limited SNP obtained in studies on migraines with aura only suggested that the two types of migraines may be similar in terms of genetic background [3]. To elucidate this point, it is important to understand the differences between the very common types of migraines. To detail migraines with aura, epigenetic markers with dynamic behavior could be used for dynamic mechanisms, such as attacks, and new candidate genes and protein-based targets can be searched with molecular modeling studies. In our study, there is no relationship between the type of migraine with and without aura, which consists of approximately equal numbers of individuals, and CHRNA7 gene expression. The effect of genes is observed in a familial, monogenic, and polygenic way, rather than these two types of migraines. A hemiplegic migraine is a rare type of migraine with aura. Mutations in genes encoding ion channels and proteins cause the disease. Functional studies in cellular and animal models show that mutations that generally make the brain more susceptible to cortical spreading depression result in glutamatergic neurotransmission and cortical hyperexcitability, a phenomenon thought to coincide with aura symptoms. It is thought that there is no relationship between CHRNA7 gene expression and types of migraines through these mechanisms and that there is no difference between the types of downregulation of the gene. > There is no relationship between gene expression and clinical findings, such as duration of pain, side, location, a form of onset, accompanying autonomy, phonophobia, photophobia, severity, MIDAS scale, presence (or absence) of provoked, mood, and equivalent in our migraine patients. These characteristics are not related to gene expression since the disease is not determinant, and they do not have a mechanism that works primarily on genes. The frequency of headache attacks ranges from approximately once a week or once a month, to once a year, for as little as an hour to three days in duration. The variability in the frequency of migraine attacks is related to both the genetic component carried by the individual and environmental trigger factors.

[5] Molecular factors in migraine

• Authors: M. Kowalska, Michal Prendecki, W. Kozubski, M. Lianeri, J. Dorszewska
• Year: 2016
• Venue: Oncotarget
• URL: https://www.semanticscholar.org/paper/2a0513926cf1a3196f26751c51e8ee15459611f2
• DOI: 10.18632/oncotarget.9367
• PMID: 27191890
• PMCID: 5226615
• Citations: 63
• Influential citations: 3
• Summary: The understanding of the molecular mechanisms of migraine, including genotype-phenotype correlations, may contribute to finding markers important for the diagnosis and treatment of this disease.
• Evidence snippets:
• Snippet 1 (score: 0.514) > Migraine is a common neurological disorder that affects 11% of adults worldwide. This disease most likely has a neurovascular origin. Migraine with aura (MA) and more common form - migraine without aura (MO) – are the two main clinical subtypes of disease. The exact pathomechanism of migraine is still unknown, but it is thought that both genetic and environmental factors are involved in this pathological process. The first genetic studies of migraine were focused on the rare subtype of MA: familial hemiplegic migraine (FHM). The genes analysed in familial and sporadic migraine are: MTHFR, KCNK18, HCRTR1, SLC6A4, STX1A, GRIA1 and GRIA3. It is possible that migraine is a multifactorial disease with polygenic influence. Recent studies have shown that the pathomechanisms of migraine involves both factors responsible for immune response and oxidative stress such as: cytokines, tyrosine metabolism, homocysteine; and factors associated with pain transmission and emotions e.g.: serotonin, hypocretin-1, calcitonin gene-related peptide, glutamate. The correlations between genetic variants of the HCRTR1 gene, the polymorphism 5-HTTLPR and hypocretin-1, and serotonin were observed. It is known that serotonin inhibits the activity of hypocretin neurons and may affect the appearance of the aura during migraine attack. The understanding of the molecular mechanisms of migraine, including genotype-phenotype correlations, may contribute to finding markers important for the diagnosis and treatment of this disease.

[6] The mysterious link between migraine aura and migraine headache

• Authors: A. Hougaard, C. Ayata, K. C. Brennan, A. M. van den Maagdenberg, M. Ashina
• Year: 2025
• Venue: PLOS Biology
• URL: https://www.semanticscholar.org/paper/6f72dcd459af475edf5ff3b2bfe686292e59eaa9
• DOI: 10.1371/journal.pbio.3003168
• PMID: 40498799
• PMCID: 12157119
• Citations: 5
• Summary: The essay highlights the complexities and conflicting data surrounding the interplay between aura and headache, emphasizing the need for further research to unravel this mystery and improve therapeutic strategies for individuals with migraine.
• Evidence snippets:
• Snippet 1 (score: 0.511) > Migraine aura is a captivating phenomenon in neurology that intrigues both clinicians and neuroscientists due to its striking clinical manifestations and complex pathophysiology. Characterized by reversible neurological disturbances that often precede the headache phase, migraine aura offers a unique window into the underpinnings of migraine -a prevalent and disabling disorder -and into the functional dynamics of the human brain. The link between migraine aura and headache has been the subject of long-standing debate, with the causal mechanisms underlying this relationship remaining unresolved. > The prevailing hypothesis implicates spreading depolarization (SD), a transient pathophysiological process of the brain responsible for aura symptoms, as a potential instigator of events culminating in migraine headache, at least in a subset of patients. This notion is supported by preclinical studies demonstrating the activation of trigeminal nociceptive neurons following the initiation of cortical SD. However, new perspectives on this mystery emerge from studies of pharmacological agents known to trigger migraine headache. These substances are believed to initiate migraine via activation of the trigeminovascular system, a term describing the sensory network originating from the trigeminal ganglion, innervating intracranial blood vessels and the meninges [1,2]. Notably, although these agents mostly act outside the central nervous system (CNS), they can still induce aura symptoms in some patients. Furthermore, monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway -large molecules that are unlikely to enter the CNS -have demonstrated efficacy in both migraine with and without aura [3]. These observations suggest a common peripheral mechanism as the initiating event of migraine attacks in both with and without auraa mechanism that could possibly be a trigger of migraine headache independently of SD. > Increasing our understanding of the migraine-aura relationship is clinically relevant since interventions targeting SD will only prevent migraine headache if SD is indeed a causative factor. In this essay, we delve into the current understanding of the complex interplay between migraine aura and headache by examining the pathophysiological processes, genetic insights, and therapeutic approaches.

[7] A comparative study on the effectiveness of topiramate and propranolol in patients with migraine with aura

• Authors: Seyed Ehsan Mohammadianinejad, Shahram Rafie, Saba Farashi
• Year: 2022
• Venue: Current Journal of Neurology
• URL: https://www.semanticscholar.org/paper/9840af9e2a03eddc814a6d57479b10e763517166
• DOI: 10.18502/cjn.v21i1.9354
• PMID: 38011452
• PMCID: 9527857
• Citations: 3
• Summary: There was no significant difference in the efficacy of topiramate and propranolol in patients with migraine with aura, and no significant relationship was found between gender and changes in the MIDAS score after the treatment in both groups.
• Evidence snippets:
• Snippet 1 (score: 0.510) > Migraine is one of the most common diseases of nervous system, which is divided into migraines with and without aura given the clinical manifestations. 1,2 Migraine is more common in females. 3 Aura is a focal neurological phenomenon that occurs before or during a migraine attack. Aura manifests commonly as visual, and much less often as sensory, speech, or motor symptoms. 4 bout 20% of patients with classic migraine experience aura symptoms before the onset of the headache. 5 Studies have suggested a genetic basis for migraine. 6 Obviously, the role of genetics in migraine with aura is greater than that in the common migraine. 4 8][9] Development of serious and permanent neurological complications in patients with classic migraine highlights the importance of controlling and treating this disease. First-line medications established as effective based on clinical evidence include divalproex, topiramate, metoprolol, propranolol, and timolol. 4 1][12][13][14] Topiramate is a sulfamate-substituted monosaccharide, derived from D-fructose. The drug reduces excitatory neurotransmission and enhances inhibitory neurotransmission, both probably involved in the pathophysiology of migraine. Topiramate, through a broad profile of action, might act at different levels: reducing nociceptive transmission through trigeminovascular modulation, and inhibiting cortical spreading depression. Topiramate is a class of anticonvulsant drugs prescribed for treatment of seizures and epilepsy in generalized colonic, partial, and tonic seizures in adults and children over 2 years of age, various epileptic syndromes, prevention of migraine attacks and treatment of bipolar disorder, schizophrenia, and stress disorder. 15 Although the exact mechanism of action of this drug is not known, several studies have reported blocking effects on sodium and calcium glutamate receptors, inhibition of the carbonic dehydrase, and strengthening effects on gamma-aminobutyric acid (GABA) receptors. 12,14

[8] Variability in oxidative stress-related genes (SOD2, CAT, GPX1, GSTP1, NOS3, NFE2L2, and UCP2) and susceptibility to migraine clinical phenotypes and features

• Authors: Maria Papasavva, M. Vikelis, V. Siokas, Martha-Spyridoula Katsarou, Emmanouil V. Dermitzakis et al.
• Year: 2023
• Venue: Frontiers in Neurology
• URL: https://www.semanticscholar.org/paper/cbb279844377728c66f39f5826f4b85db91d492d
• DOI: 10.3389/fneur.2022.1054333
• PMID: 36698892
• PMCID: 9868718
• Citations: 18
• Influential citations: 1
• Summary: The current findings possibly indicate an association of OS-related genetic variants with migraine susceptibility and clinical features, further supporting the involvement of OS and genetic susceptibility in migraine.
• Evidence snippets:
• Snippet 1 (score: 0.496) > Migraine is a complex, disabling primary headache disorder with a high worldwide prevalence, estimated ∼15%, female preponderance (3:1 female-to-male ratio), and genetic predisposition (1)(2)(3). Typically is characterized by recurrent attacks of moderate to severe throbbing headache, lasting 4-72 h, aggravated by routine physical activity and often accompanied by symptoms such as nausea, vomiting, photophobia, and/or phonophobia (4,5). About 30% of migraine cases undergo transient, reversible focal neurological symptoms, the so-called aura, occurring usually before the headache phase (6,7). Migraine clinical diagnosis is based on the International Classification of Headache Disorders 3rd Edition (ICHD-III) criteria, which subdivides migraine into two major subtypes with substantial symptomatic overlap, namely migraine without aura (MwoA) and migraine with aura (MwA) (4). > Neurological and vascular mechanisms are believed to be involved in migraine pathophysiology. Main events implicated are cortical spreading depression, activation of the trigeminovascular system, and neurogenic inflammation causing meningeal vasculature changes and the release of various migraine markers. Recent evidence supported an emerging role of metabolic abnormalities, including oxidative stress, in migraine pathogenesis (8,9). Even though some studies investigating certain markers of oxidative stress are inconsistent, cumulative findings largely indicate an alteration in physiological redox balance in migraine patients characterized by increased oxidative or nitrosative stress and/or reduced antioxidant capacity (10-12). Furthermore, oxidative stress seems to be a common denominator of the most common migraine triggers, which are likely to further enhance oxidative stress levels (13). > Migraine is a multifactorial disease, as most common complex disorders, with a substantial genetic component indicated by family and twin epidemiological studies (14-16). Thus, migraine phenotypes seem to be shaped by genetic susceptibility and exposure to environmental triggers (17,18).

[9] Is migraine a common manifestation of CADASIL? Arguments Pros

• Authors: H. Chabriat
• Year: 2025
• Venue: The Journal of Headache and Pain
• URL: https://www.semanticscholar.org/paper/2e33f2b540b4db53a1019cf4d42554449c0329df
• DOI: 10.1186/s10194-025-01980-x
• PMID: 40169951
• PMCID: 11963349
• Citations: 3
• Summary: The high prevalence and distinct MA features, as well as the data obtained at the preclinical level, strongly support a causal relationship mediated by neurovascular dysfunction in CADASIL.
• Evidence snippets:
• Snippet 1 (score: 0.489) > In a PET study of patients with CADASIL, migraine attacks with aura were detected in several individuals younger than 30 years whose cerebral blood flow, particularly cortical blood flow, was higher than that in the control population [93]. There is also a clear misalignment between the onset of migraine with aura at an early stage of the disease (sometimes during childhood) and the late appearance of ischaemic lesions or stroke events, detected several decades after the onset of attacks of migraine with aura or even after their total disappearance [21,23]. Furthermore, the occurrence of migraine with aura was not linked to the accumulation of cerebral ischaemic lesions or clinical manifestations. Recent results show exactly the opposite; patients with migraine with aura present with less ischaemic stroke after adjustment for age and vascular risk factors (personal data) [23]. In parallel, propagating depression waves induced by KCl application were facilitated at an early stage in TgNotch3R90C mutant mice, which was not observed in wild-type mice with chronic hypoperfusion [62]. Finally, no corresponding focal ischaemic lesion was observed in the cortex of CADASIL patients with migraine and aura. Moreover, there is no reason why auras usually begin with visual disturbances in CADASIL [23,94], as observed classically in migraine with aura, whereas cerebral microvasculature is diffusely affected by the disease [95]. > My opponent argues that individuals with the p.R544C variant, a specific cysteine variant of the NOTCH3 gene associated with CADASIL in East Asia, have been repeatedly detected in a large number of individuals whose clinical manifestations did not include migraine with aura, in contrast to the phenotype of Caucasian families with other mutations. This is true [96][97][98]. However, the initial vision of a unique phenotype in carriers of a pathogenic cysteine mutation in NOTCH3 has been strongly challenged. The location of the mutation within the EGFR domain of the NOTCH3 gene was recently shown to have a major influence on the accumulation of the NOTCH3 protein in the vessel wall, as well as on disease severity [99][100][101].

[10] Pharmacoinformatics elucidation of potential drug targets against migraine to target ion channel protein KCNK18

• Authors: S. A. Sehgal, Mubashir Hassan, Sajid Rashid
• Year: 2014
• Venue: Drug Design, Development and Therapy
• URL: https://www.semanticscholar.org/paper/5644fa363c13a7da92650da71d5d890ac01af4d0
• DOI: 10.2147/DDDT.S63096
• PMID: 24899801
• PMCID: 4038526
• Citations: 29
• Summary: It is proposed that selected compounds may be more potent than the previously listed drug analogs based on the binding energy values, and further analysis of these inhibitors through site-directed mutagenesis could be helpful for exploring the details of ligand-binding pockets.
• Evidence snippets:
• Snippet 1 (score: 0.487) > Migraine is a debilitating brain disease. The current understanding of the underlying pathophysiology of migraine as a strange response of the central nervous system (CNS) to numerous genetic and environmental components, is inadequate. 5,6 Polymorphisms and mutations in genes involved in neurotransmitter pathways and ion channels, hormonal mechanisms, and vascular functions are considered to be key factors for the susceptibility of migraine. 7 Human genetics and experimental pharmacology data support a migrainebased model through activation of the trigeminovascular system and neural hyperexcitability. 8,9 The prevalence of migraine is generally 3-4 times higher among women; 10 and many hypotheses have been posed for this predominance in females. 11,12 resently, the World Health Organization (WHO) recognizes migraine as a high precedence public health problem. 13,14 The disabilities linked with migraine appear to be closely associated to its severity, affecting areas such as academic performance, cognitive functioning, emotional functioning, mobility, self-care, communication, 15,16 sleep habits, [17][18][19][20][21][22] motor coordination, 23 socialization, and relationships with family members 24,25 and peers. 26 The main psychiatric and neurological disorders resulting from migraine are epilepsy, depression, somnolence, and anxiety disorders. 27 3][34] Esposito et al suggested self-esteem level as an objective tool for comparing controls with children affected with migraine without aura. 35 A rehabilitative device, the Nintendo Wii Fit Plus™ system (Kyoto, Japan) for improving balance and visuomotor skills impairment has had positive effects among children affected by migraine without aura. 36 A personality 37 and temperamental characteristics 38 assessment of mothers has resulted in better clinical and comprehensive management for migraineurs' children. > 0][41][42][43][44][45][46] The pathophysiology of migraine implicates vascular and neurological mechanisms.

[11] Mouse Models of Familial Hemiplegic Migraine for Studying Migraine Pathophysiology

• Authors: Anisa Dehghani, H. Karatas
• Year: 2019
• Venue: Current Neuropharmacology
• URL: https://www.semanticscholar.org/paper/8cd93d8fdaa5ddaf474361963d397da25f92cc54
• DOI: 10.2174/1570159X17666190513085013
• PMID: 31092180
• PMCID: 7052833
• Citations: 13
• Summary: Experimental data obtained from transgenic mice models harboring gene mutations identified in Familial Hemiplegic Migraine patients are reviewed and how they can be used to investigate the pathophysiology of migraine, including synaptic plasticity, neuroinflammation, metabolite alterations, and molecular and behavioral mecha-nisms of pain.
• Evidence snippets:
• Snippet 1 (score: 0.481) > As described above, in order to decipher migraine mechanisms, animal models of monogenic forms of migraine have been beneficial to understand the excitatory/inhibitory balance alteration in different experimental paradigms and its consequences on neurophysiology and behavior in a migraine context.There are a few key shortcomings of FHM models for investigating the pathophysiology of migraine including 1-The lack of enough information about the mechanisms of the brain network modifications in the hippocampus, cerebellum and brainstem causing FHM1 specific features of migraine-related neuronal networks in this model; 2-The lack of enough study on the neuroinflammatory cascades involved in the dysregulated excitatory/inhibitory balance.3-The lack of sufficient information about underlying mechanisms of increased CSD susceptibility in FHM2 and FHM3 mutant mice; 4-The lack of enough studies for the relevant data relating to the clinical manifestation of FHM2 and FHM3 mechanisms since the current mouse models reports have not shown significant results compared to FHM1 mouse models; and finally 5-S218L mutant mouse, with the more severe phenotype of FHM1, has been argued to be a sound model for studying migraine pathophysiology, since some researchers assume it as a model for epilepsy studies or a model for more complex neurological disorders.However, FHM mutant mice helped answer some clinically essential challenges including the link between aura and headache in a CSD model of migraine, and the relationship between geneenvironment interplay in clinical phenotypes.The transgenic mice described in the present study represent a refined tool to develop pre-clinical studies relevant to the migraine field, due to the similarity of phenotypes between patients and the mutant mice.Additionally, they will aid in future studies to investigate pain behavior in FHM and common migraine.MA in FHM is a predominant symptom and a majority of preclinical research has linked CSD events as the underlying mechanism for migraine aura; however, just about one-third of migraine patients exhibit aura symptoms.

[12] Orodispersible Tablet in Treatment of Migraine: Opportunities, Challenges and Recent Advancements

• Authors: Suhasis Bhattacharya, Tanmay Mohanta, Sujit Das, Rumpa Basak
• Year: 2021
• Venue: Journal of Drug Delivery and Therapeutics
• URL: https://www.semanticscholar.org/paper/dd7e327efd291829d909e6bc7f342474003da475
• DOI: 10.22270/jddt.v11i4.4878
• Citations: 3
• Summary: Very short half-life, quick disintegration, quick onset of action and better bioavailability brings the orodispersible tablets into the top position of the management of migraine.
• Evidence snippets:
• Snippet 1 (score: 0.480) > Migraine is a debilitating and common neurovascular illness 3 associated with symptoms of one-sided headache, nausea with or without vomiting, photophobia and/or phonophobia 4. But these symptoms are subjective and vary from patient to patient. However, A special sort of focal neurologic visual condition known as aura, affects one out of every three migraine patients 5. The major reason of the pain is due to the dilation of brain blood vessels and subsequently constricts as stimulation of nerve endings occurs near the affected blood vessels. However, whether migraine is caused by a vascular or neurological problem, the specific reason is still unknown 6 . It's been known for a long time that migraine has a strong hereditary component. Genetic research on rare monogenic subtypes, commonly well known as familial hemiplegic migraine, has revealed new information about the disease's pathophysiology. According to a recent data gene involved in ion transport at synapse and glutamatergic transmission (CACNA1A, ATP1A2 and SCN1A) casually mutate, leads to development of this ailment 7 . > Migraine can broadly classify into two major types: (i) migraine with aura and (ii) migraine without aura. Migraine with aura (also known as classical migraine) symptoms of the sensory or other central nerve systems are frequently grouped together and appear and gradually develop to form headache or other symptoms of migraine. This is recurrent and lasting for minutes. Whereas migraine without aura is common type and can last anywhere from 4 to 72 hour. The common symptoms include nausea and/or vomiting, photophobia, aggressiveness in routine behavior, phonophobia and headache in one side with pulsation 8 . The treatment of migraine is depending up on the subject history, frequency and age. For adults NSAIDs and triptans are most effective in treating acute migraine. For primary treatment NSAIDs are used. However, though it is a first line therapy but, in many cases, it becomes fail to achieve patient's initial clinical compliance. This led to use of triptans. While selecting a drug for treating migraine, formulation consideration is always prior.

[13] Epigenetic Connections of the TRPA1 Ion Channel in Pain Transmission and Neurogenic Inflammation — a Therapeutic Perspective in Migraine?

• Authors: M. Fila, E. Pawłowska, J. Szczepanska, J. Błasiak
• Year: 2023
• Venue: Molecular Neurobiology
• URL: https://www.semanticscholar.org/paper/efe577dc30c9fb411708488766d47cb032cd018b
• DOI: 10.1007/s12035-023-03428-2
• PMID: 37326902
• PMCID: 10471718
• Citations: 20
• Summary: Epigenetic connections of TRPA1 may play a role in efficacy and safety of anti-migraine therapy targeting TRP channels or CGRP and they should be further explored for efficient and safe antimigraine treatment.
• Evidence snippets:
• Snippet 1 (score: 0.467) > Targeting calcitonin gene-related peptide (CGRP) and its receptor has opened a new era in the therapy of migraine, but it is still an undertreated disease, despite its high prevalence, serious physical and mental problems for affected individuals, and high burden for societies. One of the main reasons for that is incompletely known mechanisms of migraine pathogenesis and the action of anti-migraine drugs. > The importance of genetic component in migraine pathogenesis is reported in many association studies, in particular in familial hemiplegic migraines, but without a deeper look into the mechanisms underlying observed effects (reviewed in [1]). Functional studies suggest that mutations associated with migraine result in a worsened glutamatergic neurotransmission and cortical hyperexcitability, making the brain more susceptible to cortical spreading depolarization (CSD), a phenomenon important in migraine aura symptoms. Mutations in many functionally different genes associate with migraine and this reflects a genetic complexity of molecular pathophysiology of migraine. However, two groundbreaking papers showed an important role of DNA damage and repair in the regulatory processes in the central nervous system (CNS) [2,3]. Although these discoveries were not reported in migraine cases, it may be concluded that DNA damage and repair may play a role in migraine pathogenesis [4]. Therefore, not only susceptibility variants, but also functional impairment in DNA metabolism may be essential in migraine pathogenesis. The relationship between genotype and phenotype, crucial for disease occurrence, is dictated by gene expression, which is principally regulated at the transcriptional and translational levels. Epigenetic regulation of gene expression, manifested by changes in DNA methylation, histone modifications, and action of non-coding RNAs, collectively creating the cellular epigenetic pattern, plays an important role in acquiring and maintaining normal or pathological brain phenotype (reviewed in [5]). Also, the expression of migraine-susceptibility variants of genes may result from disturbed epigenetic regulation of normal variants of genes important in migraine.

[14] Is there a role of calcitonin gene-related peptide in cortical spreading depression mechanisms?– argument con.

• Authors: A. Melo-Carrillo
• Year: 2025
• Venue: The Journal of Headache and Pain
• URL: https://www.semanticscholar.org/paper/8b9d0ccd13ab64fe0e4fbb26fb006e6d982dff47
• DOI: 10.1186/s10194-025-02012-4
• PMID: 40295929
• PMCID: 12036166
• Citations: 3
• Summary: Evidence is evaluated suggesting that CGRP is not directly involved in CSD initiation or propagation but may contribute to nociceptive activation associated with migraine, highlighting distinct pathways for aura and headache pathophysiology.
• Evidence snippets:
• Snippet 1 (score: 0.466) > Cortical spreading depression (CSD) is a wave of neuronal and glial depolarization followed by suppressed neural activity, thought to underlie migraine aura. While Calcitonin Gene-Related Peptide (CGRP) is well established in migraine pathophysiology, its role in CSD remains uncertain. This comment evaluates evidence suggesting that CGRP is not directly involved in CSD initiation or propagation but may contribute to nociceptive activation associated with migraine. While some studies report CGRP-related effects on CSD susceptibility, methodological limitations raise concerns about their interpretation. Electrophysiological data indicate that CGRP does not influence the ionic mechanisms driving CSD. However, CGRP plays a key role in sensitizing nociceptive neurons, and CGRP-targeting drugs effectively modulate migraine pain without altering CSD dynamics. Clinical findings further suggest that peripheral CGRP inhibition reduces headache burden, potentially allowing the brain to recover from chronic pain states. In conclusion, while CGRP is integral to migraine pain modulation, its direct involvement in CSD appears minimal, highlighting distinct pathways for aura and headache pathophysiology.

[15] Multi-omics approaches to deciphering complex pathological mechanisms of migraine: a systematic review

• Authors: Jiaojiao Liu, Qiaosheng Ren, Boxuan Du, Xian Liu, Yuqiu An et al.
• Year: 2025
• Venue: Frontiers in Pharmacology
• URL: https://www.semanticscholar.org/paper/8d3095f24f87b2c87f94f1adb09c7a66070df395
• DOI: 10.3389/fphar.2024.1452614
• PMID: 39850553
• PMCID: 11754399
• Citations: 4
• Summary: This systematic review aims to synthesize the findings of multi-omics studies on migraine to further elucidate the complex mechanisms of disease onset, thereby laying a scientific foundation for identifying new therapeutic targets.
• Evidence snippets:
• Snippet 1 (score: 0.465) > Background Migraine represents a chronic neurological disorder characterized by high prevalence, substantial disability rates, and significant economic burden. Its pathogenesis is complex, and there is currently no cure. The rapid progress in multi-omics technologies has provided new tools to uncover the intricate pathological mechanisms underlying migraine. This systematic review aims to synthesize the findings of multi-omics studies on migraine to further elucidate the complex mechanisms of disease onset, thereby laying a scientific foundation for identifying new therapeutic targets. Methods We conducted a comprehensive systematic review, specifically focusing on clinical observational studies that investigate various aspects of migraine through the integration of genomics, transcriptomics, proteomics, and metabolomics. Our search encompassed multiple databases including PubMed, EMBASE, the Web of Science Core Collection, the Cochrane Library, China National Knowledge Infrastructure, the Chinese Science and Technology Periodical Database, the Wanfang database, and the China Biology Medicine Database to cover studies from database inception until 20 March 2024., The scope of our review included various aspects of migraine such as ictal and interictal phases; episodic or chronic migraine; menstrual-related migraine; and migraine with or without aura (PROSPERO registration number: CRD42024470268). Results A total of 38 studies were ultimately included, highlighting a range of genetic variations, transcriptional abnormalities, protein function alterations, and disruptions in metabolic pathways associated with migraine.These multi-omics findings underscore the pivotal roles played by mitochondrial dysfunction, inflammatory responses, and oxidative stress in the pathophysiology of migraine. Conclusion Multi-omics approaches provide novel perspectives and tools for comprehending the intricate pathophysiology of migraine, facilitating the identification of potential biomarkers and therapeutic targets. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=470268, identifier CRD42024470268.

[16] The Current Status of Treatment among Migraine Patients in Bangladesh

• Authors: M. Hasan
• Year: 2019
• Venue: journal of medical science and clinical research
• URL: https://www.semanticscholar.org/paper/1c64e6175e6abf526eedc159d8d8762941937d2d
• DOI: 10.18535/jmscr/v7i12.145
• Summary: It can be concluded from the study that propranolol should be used as an agent for the prophylaxis of migraine.
• Evidence snippets:
• Snippet 1 (score: 0.463) > Migraine is a neurological disease of which the most common symptom is an intense headache and is a common disabling primary headache disorder. Migraine, the second most common cause of headache, and the most common http://jmscr.igmpublication.org/home/ ISSN (e)-2347-176x ISSN (p) 2455-0450 DOI: https://dx.doi.org/10.18535/jmscr/v7i12.145 headache-related and indeed neurologic, cause of disability in the world, afflicts approximately 15% of women and 6% of men over a 1-year period. 1 Migraine has two major subtypes. 2 Migraine without aura is a clinical syndrome characterized by headache with specific features and associated symptoms. Migraine with aura is primarily characterized by the transient focal neurological symptoms that usually precede or sometimes accompany the headache. Some patients also experience a premonitory phase, occurring hours or days before the headache, and a headache resolution phase. Premonitory and resolution symptoms include hyperactivity, hypo activity, depression, cravings for particular foods, repetitive yawning, fatigue and neck stiffness and/or pain. 2 Since migraine attacks are often frequent they require management with agents that reduce their number. Such agents, although often effective, are ill-understood. It has been suggested that they work through four main mechanisms. 5-HT antagonism, modulation of plasma protein extravasation, modulation of central aminergic control mechanisms and membrane stabilizing effects through actions at voltage-sensitive channels. 16 The mechanism of action is unrelated to its antidepressant activity. Flunarizine is a calcium channel blocker, most widely prescribed drugs for adults and adolescent. Propranolol is also one of the most commonly prescribed drugs for migraine prophylaxis. Exactly how β-blockers decrease the frequency of migraine attacks is not certain. The mechanism of action of betablockers in migraine prophylaxis is unknown; hypothesis include inhibition of central betareceptors modulation of 5-HT receptor activity, and cross-regulation of serotonergic pathways. 1

[17] Advances in genetics of migraine

• Authors: H. Sutherland, C. L. Albury, L. Griffiths
• Year: 2019
• Venue: The Journal of Headache and Pain
• URL: https://www.semanticscholar.org/paper/dbecbd940c2e96f54a83ab09b7dbe42ea36ddb55
• DOI: 10.1186/s10194-019-1017-9
• PMID: 31226929
• PMCID: 6734342
• Citations: 189
• Influential citations: 9
• Summary: A comprehensive knowledge of the genetic factors underpinning migraine will lead to improved understanding of molecular mechanisms and pathogenesis, to enable better diagnosis and treatments for migraine sufferers.
• Evidence snippets:
• Snippet 1 (score: 0.462) > BackgroundMigraine is a complex neurovascular disorder with a strong genetic component. There are rare monogenic forms of migraine, as well as more common polygenic forms; research into the genes involved in both types has provided insights into the many contributing genetic factors. This review summarises advances that have been made in the knowledge and understanding of the genes and genetic variations implicated in migraine etiology.FindingsMigraine is characterised into two main types, migraine without aura (MO) and migraine with aura (MA). Hemiplegic migraine is a rare monogenic MA subtype caused by mutations in three main genes - CACNA1A, ATP1A2 and SCN1A - which encode ion channel and transport proteins. Functional studies in cellular and animal models show that, in general, mutations result in impaired glutamatergic neurotransmission and cortical hyperexcitability, which make the brain more susceptible to cortical spreading depression, a phenomenon thought to coincide with aura symptoms. Variants in other genes encoding ion channels and solute carriers, or with roles in regulating neurotransmitters at neuronal synapses, or in vascular function, can also cause monogenic migraine, hemiplegic migraine and related disorders with overlapping symptoms. Next-generation sequencing will accelerate the finding of new potentially causal variants and genes, with high-throughput bioinformatics analysis methods and functional analysis pipelines important in prioritising, confirming and understanding the mechanisms of disease-causing variants.With respect to common migraine forms, large genome-wide association studies (GWAS) have greatly expanded our knowledge of the genes involved, emphasizing the role of both neuronal and vascular pathways. Dissecting the genetic architecture of migraine leads to greater understanding of what underpins relationships between subtypes and comorbid disorders, and may have utility in diagnosis or tailoring treatments. Further work is required to identify causal polymorphisms and the mechanism of their effect, and studies of gene expression and epigenetic factors will help bridge the genetics with migraine pathophysiology.ConclusionsThe complexity of migraine disorders is mirrored by their genetic complexity. A comprehensive knowledge of the genetic factors underpinning migraine will lead to improved understanding of molecular mechanisms and pathogenesis

[18] Gene expression microarray analysis of the spinal trigeminal nucleus in a rat model of migraine with aura

• Authors: Ruozhuo Liu, Shengyuan Yu, Fengpeng Li, E. Qiu
• Year: 2012
• Venue: Neural Regeneration Research
• URL: https://www.semanticscholar.org/paper/4b8ff3c233cc758a4b24fa72529f54220707a584
• DOI: 10.3969/j.issn.1673-5374.2012.25.002
• PMID: 25624821
• PMCID: 4298885
• Citations: 5
• Summary: Real-time quantitative reverse transcription-PCR and bioinformatics analysis indicated that these genes are involved in motility, cell migration, CO2/nitric oxide homeostasis and signal transduction, which indicates that cortical spreading depression can trigger migraine with aura and activate the trigeminal vascular system.
• Evidence snippets:
• Snippet 1 (score: 0.461) > Cortical spreading depression (CSD), first described in 1944 [1] , is characterized by a slow spreading of cellular depolarization in neurons and glial cells at a rate of 2-5 mm/min. Clinically, CSD is often accompanied by neurological diseases, such as migraine with aura, sudden convulsions, cerebral infarction and ischemic brain injury [2] . Although it is generally accepted that CSD may induce migraine with aura, the underlying mechanisms remain unclear [3][4][5] . The change in cerebral blood flow following CSD suggests that vasoactive molecules may play important roles in CSD-induced migraine with aura [6][7][8] . Several studies have examined the impact of CSD on gene expression. Following CSD, the mRNA and protein levels of nitric oxide synthase are increased in cortical astrocytes [9] . The spinal trigeminal nucleus plays an important role in migraine headaches as a primary headache nerve center. Recent studies have shown that CSD can activate the trigeminal vascular system [10] . In order to explore CSD-induced changes in gene expression in the spinal trigeminal nucleus, we first established a rat model of migraine with aura by high potassium stimulation and then conducted gene expression microarray analysis of the trigeminal vascular system. This study aimed to provide important insight into the molecular mechanism of CSD-induced migraine with aura.

[19] Migraine and neuroinflammation: the inflammasome perspective

• Authors: O. Kurşun, M. Yemisci, A. M. van den Maagdenberg, H. Karatas
• Year: 2021
• Venue: The Journal of Headache and Pain
• URL: https://www.semanticscholar.org/paper/0b77a3ff9880c41a016bcf9a2736db950b9608fb
• DOI: 10.1186/s10194-021-01271-1
• PMID: 34112082
• PMCID: 8192049
• Citations: 177
• Influential citations: 6
• Summary: Findings of cortical spreading depolarization (CSD)-induced neuroinflammatory signaling in brain parenchyma from the inflammasome perspective are highlighted and neuroinflammatory pathways, specifically those involving inflammaome proteins, seem promising candidates as treatment targets, and perhaps even biomarkers, in migraine.
• Evidence snippets:
• Snippet 1 (score: 0.459) > Migraine pathophysiology is the result of interactions of neurons, glial cells, the vasculature, and inflammatory signaling, cumulating into a highly debilitating neurological disorder that is characterized by recurrent unilateral headaches that last 4 to 72 h and that are accompanied by other features, such as nausea and photo/phonophobia [1]. Two main types of migraine are distinguished based on the presence of an aura (preceding the headache) and that is characterized by slowly spreading visual and sensory disturbances, hence [1], migraine with aura (MA) and migraine without aura (MO). Migraine affects over 15% of the general population and is among the most prevalent and disabling chronic disease conditions, also in terms of morbidity and lost productivity due to absenteeism of work [2]. Migraine occurs three times more often in women than men [3]. The high economic burden of migraine loads heavily on healthcare systems of countries worldwide [4]. Therefore, reducing the burden of migraine remains key but the development of better treatment options is hampered by our incomplete understanding of the pathophysiology of migraine through basic and clinical research models. > Neuroinflammation is regarded as the adaptive reaction initiated by noxious stimuli, such as infection, injury and tissue stress, and plays an important role in the pathophysiology of various diseases of the central nervous system [5]. In the context of migraine, neurogenic neuroinflammation is defined by inflammatory reactions in the central and peripheral parts of the trigeminovascular system in response to neuronal activity [6]. Although the term is mainly applied to central nervous system (CNS) components it is also relevant to peripheral nervous system (PNS) structures, such as the trigeminal ganglion. The immune system is divided into a more primitive innate immune system and an acquired or adaptive immune system, each of which contain both humoral and cellular immune elements. Over the past decade, there has been a surge in information regarding the composition and actions of the innate immune system of the CNS, which includes microglia, trafficking macrophages and astrocytes [7].

[20] Role of dopaminergic system in migraine

• Authors: A. Cherchi, Erminia Stochino, M. Piccardi, M. Del Zompo
• Year: 2001
• Venue: The Journal of Headache and Pain
• URL: https://www.semanticscholar.org/paper/5780715472efff4dc809537ade29b1c178e6e6c3
• DOI: 10.1007/s101940170009
• PMCID: 3451826
• Citations: 4
• Summary: A positive association between the “dopaminergic” phenotype of migraine without aura and the D2 receptor gene has been found and this finding reaffirms the role of central neurogenic mechanisms in the regulation of the cerebral circulation and further supports the major role of dopamine in the neurogenic mechanism of migraine.
• Evidence snippets:
• Snippet 1 (score: 0.456) > The theory that hypersensitivity of the DA system is involved in the pathogenesis of migraine has been supported by various authors on the basis of clinical, pharmacological and, recently, genetic evidence. ther supports the major role of dopamine in the neurogenic mechanisms of migraine. Various studies have been carried out to verify the involvement of DA in migraine pathogenesis using molecular genetics as a tool. A positive association between the "dopaminergic" phenotype of migraine without aura and the D2 receptor gene has been found. To explain dopaminergic hypersensitivity in migraine without aura, we will study the genes encoding proteins involved in the signal transduction system.

Notes

• This provider combines search_papers_by_relevance with snippet_search.
• No synthesis or second-stage model call is performed.