Migraine Pathology Research Articles

Exploring the Spectrum of Migraine: Beyond Auras and Multisensory Unusual Experiences

The aim of this study is to compare the visual and non-visual aura experiences of migraine patients. By analyzing demographic data, pain intensity, attack frequency, and migraine-related disability, this research seeks to identify patterns and differences in sensory experiences among individuals diagnosed with migraine according to the International Headache Society criteria. This study involves 50 participants aged 18 to 56 years who have experienced unusual sensory experiences in the auditory, visual, olfactory, somatic-tactile, and gustatory domains. The findings will provide insights into the relationship between different types of aura experiences and various demographic and clinical factors, contributing to a deeper understanding of migraine pathology and potentially informing better-targeted treatments and management strategies.

MIGRAINE

Background Migraine is a prevalent neurological disorder characterized by chronic headaches, significantly impacting the global population. This comprehensive review aims to advance the understanding of migraine pathogenesis and treatment, focusing on molecular markers and novel therapeutic strategies. Material Molecular markers such as calcitonin gene-related peptide (CGRP) and their role in migraine development. Traditional medical treatments and emerging therapeutic strategies, including neuromodulation, are analyzed for their effectiveness and limitations. Clinical studies and imaging techniques are leveraged to identify key mechanisms and triggers in migraine pathology. Approximately 95% of people experience a headache at some point, with migraines being a significant contributor. Migraine is recognized by the World Health Organization as one of the top ten causes of disability globally, particularly affecting women. CGRP is identified as a crucial factor in migraine development. Inhibitors targeting CGRP have shown significant effectiveness in managing migraines. Other molecular markers, including proinflammatory cytokines and neurotransmitters, are discussed for their roles in pain transmission and migraine pathophysiology. Traditional treatments, such as triptans and NSAIDs, are evaluated alongside new therapies, including CGRP inhibitors and neuromodulation techniques. Neuromodulation, involving devices like external trigeminal nerve stimulators, shows promise in migraine management. Genetic markers associated with familial hemiplegic migraine (FHM) and common migraine forms are reviewed. Recent genome-wide association studies (GWAS) have identified several genetic variants linked to migraine susceptibility. Conclusion This presentation enhances the understanding of migraine pathogenesis and introduces novel therapeutic possibilities. By focusing on molecular markers like CGRP and exploring advanced treatment options, the study aims to improve migraine management and patient care. The findings underscore the need for continued research and innovation in migraine treatments to reduce the global burden of this debilitating condition.

Chronic overlapping pain conditions and nociplastic pain

Chronic Overlapping Pain Conditions (COPCs) are a subset of chronic pain conditions commonly comorbid with one another and more prevalent in women and assigned female at birth (AFAB) individuals. Pain experience in these conditions may better fit with a new mechanistic pain descriptor, nociplastic pain, and nociplastic pain may represent a shared underlying factor among COPCs. We applied GenomicSEM common-factor genome wide association study (GWAS) and multivariate transcriptome-wide association (TWAS) analyses to existing GWAS output for six COPCs in order to find genetic variation associated with nociplastic pain, followed by genetic correlation (linkage-disequilibrium score regression), gene-set and tissue enrichment analyses. We found 24 independent single nucleotide polymorphisms (SNPs), and 127 unique genes significantly associated with nociplastic pain, and showed nociplastic pain to be a polygenic trait with significant SNP-heritability. We found significant genetic overlap between multisite chronic pain and nociplastic pain, and to a smaller extent with rheumatoid arthritis and a neuropathic pain phenotype. Tissue enrichment analyses highlighted cardiac and thyroid tissue, and gene set enrichment analyses emphasized potential shared mechanisms in cognitive, personality, and metabolic traits and nociplastic pain along with distinct pathology in migraine and headache. We use a well-powered network approach to investigate nociplastic pain using existing COPC GWAS output, and show nociplastic pain to be a complex, heritable trait, in addition to contributing to understanding of potential mechanisms in development of nociplastic pain.

Antimigraine activity of Asarinin by OPRM1 pathway with multifaceted impacts through network analysis

Migraine is a debilitating neurological disorder impacting millions worldwide. Calcitonin Gene-Related Peptide (CGRP) has emerged as a key player in migraine pathophysiology, leading to the development of targeted therapies. This study reviews novel CGRP-targeted treatments, including monoclonal antibodies small molecule inhibitors/nutraceuticals and introduces Asarinin as a potential modulator of the pathway. Asarinin, a natural compound found in various plants, is examined for its pharmacological potential in migraine management. Pharmacokinetic assessments, toxicological modelling, molecular property analysis, and network pharmacology were conducted. Molecular docking and dynamics studies with CGRP reveal potential interactions, providing a foundation for understanding Asarinin's therapeutic effects. Asarinin's favourable pharmacokinetics, safety profile, and bioactivity, supporting its candidacy as a therapeutic agent. In-depth molecular docking studies with the CGRP receptor (PDB: 6ZHO) demonstrate strong binding affinity (− 10.3kcal/mol), while molecular dynamics simulations unveil the dynamic behavior of the Asarinin-CGRP complex, (− 10.53 kcal/mol) for Atogepant-CGRP complex. Network analysis highlights key proteins in migraine pathology, indicating Asarinin's potential efficacy. The groundwork for future investigations, suggests Asarinin as a promising candidate for migraine management by targeting OPRM1 pathway. The integration of diverse assessments provides a comprehensive understanding of Asarinin's potential and paves the way for further preclinical and clinical research.

Functional properties of a disease mutation for migraine in Kv2.1/6.4 channels

Voltage-gated potassium (Kv) channels are integral to cellular excitability, impacting the resting membrane potential, repolarization, and shaping action potentials in neurons and cardiac myocytes. Structurally, Kv channels are homo or heterotetramers comprising four α-subunits, each with six transmembrane segments (S1–S6). Silent Kv (KvS), includes Kv5.1, Kv6.1–6.4, Kv8.1–8.2, and Kv9.1–9.3, they do not form functional channels on their own but modulate the properties of heteromeric channels. Recent studies have identified the Kv6.4 subunit as a significant modulator within heteromeric channels, such as Kv2.16.4. The Kv2.16.4 heteromer exhibits altered biophysical properties, including a shift in voltage-dependent inactivation and a complex activation. Current genetic studies in migraine patients have revealed a single missense mutation in the Kv6.4 gene. The single missense mutation, L360P is in the highly conserved S4–S5 linker region. This study aims to demonstrate the biophysical effects of the L360P mutation in Kv2.1 6.4 channels with a fixed 2:2 stoichiometry, using monomeric (Kv2.1/6.4) and tandem dimer (Kv2.1_6.4) configurations. Our findings suggest that the L360P mutation significantly impacts the function and regulation of Kv2.1/6.4 channels, providing insights into the molecular mechanisms underlying channel dysfunction in migraine pathology.

A role of NLRP3 and MMP9 in migraine progression: a systematic review of translational study.

Migraines affect one billion individuals globally, with a higher occurrence among young adults and women. A significant survey in the United States indicated that 17.1% of women and 5.6% of men suffer from migraines. This study seeks to investigate the potential connection between NLRP3 and MMP9 in migraine pathology. The research involved searching databases such as PubMed, Scopus, Science Direct, Google Scholar, and Proquest, with the search concluding on March 31, 2024. Following PRISMA guidelines, PICO data were collected, focusing exclusively on animal models induced by Nitroglycerine (10 mg/kg), while excluding clinical studies. The study, originally registered in Prospero Reg. No. CRD42022355893, conducted bias analysis using SYRCLE's RoB tool and evaluated author consensus using GraphPad v9.5.1. Out of 7,359 search results, 22 papers met the inclusion criteria. Inter-rater reliability among reviewers was assessed using Cohen's kappa statistics. This review summarizes 22 preclinical studies on Nitroglycerin (NTG), NLRP3, MMP9, and related biomarkers in migraine. They reveal that NTG, especially at 10 mg/kg, consistently induces migraine-like symptoms in rodents by activating NLRP3 inflammasome and stimulating proinflammatory molecule production. https://www.crd.york.ac.uk/prospero/, CRD42022355893.

A Review of the CACNA Gene Family: Its Role in Neurological Disorders.

Calcium channels are specialized ion channels exhibiting selective permeability to calcium ions. Calcium channels, comprising voltage-dependent and ligand-gated types, are pivotal in neuronal function, with their dysregulation is implicated in various neurological disorders. This review delves into the significance of the CACNA genes, including CACNA1A, CACNA1B, CACNA1C, CACNA1D, CACNA1E, CACNA1G, and CACNA1H, in the pathogenesis of conditions such as migraine, epilepsy, cerebellar ataxia, dystonia, and cerebellar atrophy. Specifically, variants in CACNA1A have been linked to familial hemiplegic migraine and epileptic seizures, underscoring its importance in neurological disease etiology. Furthermore, different genetic variants of CACNA1B have been associated with migraine susceptibility, further highlighting the role of CACNA genes in migraine pathology. The complex relationship between CACNA gene variants and neurological phenotypes, including focal seizures and ataxia, presents a variety of clinical manifestations of impaired calcium channel function. The aim of this article was to explore the role of CACNA genes in various neurological disorders, elucidating their significance in conditions such as migraine, epilepsy, and cerebellar ataxias. Further exploration of CACNA gene variants and their interactions with molecular factors, such as microRNAs, holds promise for advancing our understanding of genetic neurological disorders.

Is functional MRI meaningful in migraine?

Functional magnetic resonance imaging (fMRI) is an imaging method that enables us to understand brain anatomy, mapping and its function. While fMRI was previously used in experimental studies, it has now been used in clinical studies. Imaging in fMRI is based on measuring the increase in regional blood flow caused by cortical activation. fMRI indirectly demonstrates neural activation by detecting increases in oxygenation. fMRI relies on the sensitivity of magnetic resonance signals to changes in deoxyhemoglobin levels or perfusion, reflecting the metabolic and hemodynamic responses associated with neural activation. Imaging is arranged in the clinic for primary headaches if needed for a differential diagnosis. However, imaging studies are utilized in scientific research to elucidate the pathophysiology. Migraine is a common episodic disorder characterized by recurring attacks. Investigating the functional structure of the brain during both attack and interictal periods is crucial in understanding migraine pathology. However, capturing patients' migraine attacks for monitoring purposes without treatment is considered unethical in many countries. Moreover, conducting such studies is hindered by the requirement for prolonged hospital stays and extended imaging times, which significantly increase costs. Despite the challenges of conducting research in migraine patients, fMRI stands out as an excellent imaging method for investigating the functional brain structures involved in this episodic disorder. Several fMRI studies have yielded valuable insights into the pathophysiology of migraine. fMRI is believed to offer valuable guidance in refining our understanding of migraine-specific mechanisms, facilitating biomarker studies for migraine activity, and elucidating abnormal functions in regions affected by migraine. Monitoring treatment response using biomarkers is anticipated to be an effective tool for identifying targets for migraine treatment, including assessing treatment efficacy in the development of new migraine-specific therapies.

Cryo-EM Structure of the Human Amylin 1 Receptor in Complex with CGRP and Gs Protein.

Inhibition of calcitonin gene-related peptide (CGRP) or its cognate CGRP receptor (CGRPR) has arisen as a major breakthrough in the treatment of migraine. However, a second CGRP-responsive receptor exists, the amylin (Amy) 1 receptor (AMY1R), yet its involvement in the pathology of migraine is poorly understood. AMY1R and CGRPR are heterodimers consisting of receptor activity-modifying protein 1 (RAMP1) with the calcitonin receptor (CTR) and the calcitonin receptor-like receptor (CLR), respectively. Here, we present the structure of AMY1R in complex with CGRP and Gs protein and compare it with the reported structures of the AMY1R complex with rat amylin (rAmy) and the CGRPR in complex with CGRP. Despite similar protein backbones observed within the receptors and the N- and C-termini of the two peptides bound to the AMY1R complexes, they have distinct organization in the peptide midregions (the bypass motif) that is correlated with differences in the dynamics of the respective receptor extracellular domains. Moreover, divergent conformations of extracellular loop (ECL) 3, intracellular loop (ICL) 2, and ICL3 within the CTR and CLR protomers are evident when comparing the CGRP bound to the CGRPR and AMY1R, which influences the binding mode of CGRP. However, the conserved interactions made by the C-terminus of CGRP to the CGRPR and AMY1R are likely to account for cross-reactivity of nonpeptide CGRPR antagonists observed at AMY1R, which also extends to other clinically used CGRPR blockers, including antibodies.

Models of Trigeminal Activation: Is There an Animal Model of Migraine?

Migraine, recognized as a severe headache disorder, is widely prevalent, significantly impacting the quality of life for those affected. This article aims to provide a comprehensive review of the application of animal model technologies in unraveling the pathomechanism of migraine and developing more effective therapies. It introduces a variety of animal experimental models used in migraine research, emphasizing their versatility and importance in simulating various aspects of the condition. It details the benefits arising from the utilization of these models, emphasizing their role in elucidating pain mechanisms, clarifying trigeminal activation, as well as replicating migraine symptoms and histological changes. In addition, the article consciously acknowledges the inherent limitations and challenges associated with the application of animal experimental models. Recognizing these constraints is a fundamental step toward fine-tuning and optimizing the models for a more accurate reflection of and translatability to the human environment. Overall, a detailed and comprehensive understanding of migraine animal models is crucial for navigating the complexity of the disease. These findings not only provide a deeper insight into the multifaceted nature of migraine but also serve as a foundation for developing effective therapeutic strategies that specifically address the unique challenges arising from migraine pathology.

Benefit of Dietary Supplementation of Nutraceuticals as an Integrative Approach for Management of Migraine: Evidence From Preclinical and Clinical Studies.

To provide information from preclinical and clinical studies on the biological activity and health benefits of dietary inclusion of nutraceuticals as a safe, effective, non-pharmacological approach for the treatment of migraine. There is emerging evidence of the therapeutic benefit of nutraceuticals to inhibit oxidative stress, suppress inflammation, and prevent changes in the normal gut microbiome, which are implicated in migraine pathology. Nutraceuticals can be enriched in polyphenols, which act as molecular scavengers to reduce the harmful effects of reactive oxygen species and phytosterols that suppress inflammation. Nutraceuticals also function to inhibit dysbiosis and to maintain the commensal intestinal bacteria that produce anti-inflammatory molecules including short-chain fatty acids that can act systemically to maintain a healthy nervous system. Dietary inclusion of nutraceuticals that exhibit antioxidant, anti-inflammatory, and anti-nociceptive properties and maintain the gut microbiota provides a complementary and integrative therapeutic strategy for migraine.

Blood donation and migraine relief: A national population cohort study in Denmark.

Migraine is a prevalent neurological headache disorder. Due to challenges associated with finding effective treatment, many individuals with migraine feel compelled to explore alternative treatment strategies, such as blood donation, hypothesized to provide migraine relief. Through logistic, Poisson, and Cox regression methods, we examined the links between migraine and blood donation activities in two population cohorts: Danish blood donors in the Scandinavian Donations and Transfusions Database (SCANDAT-DK, N >1 million) and the Danish Blood Donor Study (N ~ 100,000). SCANDAT-DK analyses showed no link between migraine and the propensity to become a blood donor among males (odds ratio [OR]Males = 0.95 [95% Confidence Interval: 0.86-1.04], and a reduced propensity among females ORFemales = 0.88 [0.83-0.93]). The incidence of migraine was not reduced upon blood donation (standardized incidence ratio [SIR]Males = 0.94 [0.83-1.06]; SIRFemales = 1.04 [0.99-1.10]). Donors with migraine demonstrated longer intervals between donations (hazard ratio [HR]Males = 0.87 [0.85-0.91], HRFemales = 0.80 [0.78-0.82]), and an increased risk of donor lapse (ORMales = 1.23 [1.14-1.32]; ORFemales = 1.28 [1.22-1.33]). Results were corroborated in DBDS using self-reported migraine. Genetic predisposition to migraine associated with longer intervals in females (HRFemales = 0.98 [0.97-0.99]), but not in males. Our findings do not support the hypothesis that blood donation serves as a viable treatment strategy among migraine patients. Future prospective investigations may help to elucidate the underlying biological mechanisms by which blood donation may influence migraine pathology.

Comprehensive analysis of genetic associations and single-cell expression profiles reveals potential links between migraine and multiple diseases: a phenome-wide association study.

Migraine is a common neurological disorder that affects more than one billion people worldwide. Recent genome-wide association studies have identified 123 genetic loci associated with migraine risk. However, the biological mechanisms underlying migraine and its relationships with other complex diseases remain unclear. We performed a phenome-wide association study (PheWAS) using UK Biobank data to investigate associations between migraine and 416 phenotypes. Mendelian randomization was employed using the IVW method. For loci associated with multiple diseases, pleiotropy was tested using MR-Egger. Single-cell RNA sequencing data was analyzed to profile the expression of 73 migraine susceptibility genes across brain cell types. qPCR was used to validate the expression of selected genes in microglia. PheWAS identified 15 disorders significantly associated with migraine, with one association detecting potential pleiotropy. Single-cell analysis revealed elevated expression of seven susceptibility genes (including ZEB2, RUNX1, SLC24A3, ANKDD1B, etc.) in brain glial cells. And qPCR confirmed the upregulation of these genes in LPS-treated microglia. This multimodal analysis provides novel insights into the link between migraine and other diseases. The single-cell profiling suggests the involvement of specific brain cells and molecular pathways. Validation of gene expression in microglia supports their potential role in migraine pathology. Overall, this study uncovers pleiotropic relationships and the biological underpinnings of migraine susceptibility.

Potential genetic polymorphism of matrix metalloproteinase (MMP)-9 in Iranian migraine patients with Toxoplasma gondii infection.

Toxoplasma gondii is an intracellular protozoan parasite that causes neuroinflammation in the brain and a constant need for peripheral leukocyte migration. Matrix metalloproteinase 9 (MMP-9) can play a major role in this neuroinflammation and be implicated in some neurological disorders, such as migraines. Therefore, the genetic polymorphism evaluation of MMP-9 in migraine patients with T. gondii infection was performed. One hundred fourteen migraine patients and 114 healthy controls were evaluated for the presence of anti-Toxoplasma IgG antibodies. Seventy-two migraine patients and 40 healthy controls were randomly selected for assessment of the MMP 9-1562C/T genetic polymorphism. In the preliminary examination, 61 (53.5%) migraine patients and 43 (37.3%) healthy controls were positive for IgG antibodies, with a significant association between T. gondii seropositivity and migraine (OR = 1.90; 95% CI = 1.21-3.223; P = 0.012). Genetic distribution for the polymorphism was not in Hardy-Weinberg equilibrium in cases but showed no significant variation in control groups (P = 0.03 and P = 0.180, respectively). A significant preponderance of the CT + TT genotype was found in migraine subjects compared to controls (P = 0.042) (OR, 1.77, CI, 1.013-2.229). The homozygote muted allele TT had a higher rate in migraine patients (6.9%). There were significant differences in CT + TT genotype between T. gondii positive and negative migraine patients (P = 0.024), but T allele frequencies had no significant variation (OR 1.7 CI, 1.084-2.44 and 0.42 CI, 0.044-3.97, respectively). In conclusion, the results may provide the first evidence for the involvement of the MMP-9 gene polymorphism in the mechanism of migraine pathology following Toxoplasma infection.

Migraine Comorbidities.

Novel knowledge about the interrelationships and reciprocal effects of migraine and epilepsy, migraine and mood disorders, or migraine and irritable bowel syndrome has emerged in recent decades. Over time, comorbid pathologies associated with migraine that share common physiopathological mechanisms were studied. Among these studied pathologies is epilepsy, a disorder with common ion channel dysfunctions as well as dysfunctions in glutamatergic transmission. A high degree of neuronal excitement and ion channel abnormalities are associated with epilepsy and migraine and antiepileptic drugs are useful in treating both disorders. The coexistence of epilepsy and migraine may occur independently in the same individual or the two may be causally connected. The relationship between cortical spreading depression (CSD) and epileptic foci has been suggested by basic and clinical neuroscience research. The most relevant psychiatric comorbidities associated with migraine are anxiety and mood disorders, which influence its clinical course, treatment response, and clinical outcome. The association between migraine and major depressive disorder can be explained by a robust molecular genetic background. In addition to its role as a potent vasodilator, CGRP is also involved in the transmission of nociception, a phenomenon inevitably linked with the stress and anxiety caused by frequent migraine attacks. Another aspect is the role of gut microbiome in migraine's pathology and the gut-brain axis involvement. Irritable bowel syndrome patients are more likely to suffer migraines, according to other studies. There is no precise explanation for how the gut microbiota contributes to neurological disorders in general and migraines in particular. This study aims to show that migraines and comorbid conditions, such as epilepsy, microbiota, or mood disorders, can be connected from the bench to the bedside. It is likely that these comorbid migraine conditions with common pathophysiological mechanisms will have a significant impact on best treatment choices and may provide clues for future treatment options.

Integration of single-nucleus RNA sequencing and network disturbance to elucidate crosstalk between multicomponent drugs and trigeminal ganglia cells in migraine

Ethnopharmacological relevanceMigraine is caused by hyperactivity of the trigeminovascular system, where trigeminal ganglia (TG) plays an important role. TG is composed of multiple neuronal and non-neuronal cell types, which is related to “neuro-inflammation-vascular” disorder in migraine. Tou Tong Ning capsule (TTNC), a CFDA-approved traditional Chinese medicine for treating migraine, has the characteristics of “multicomponents, multitargets, multipathways". Aim of the studyTo clarify the mechanism of TTNC and elucidate crosstalk between multicomponent drugs and neuronal and non-neuronal functions and cells in migraine. Materials and methodsWe integrated single-nucleus RNA sequencing and a quantitative evaluation algorithm of the disturbance of multitarget drugs on the disease network and explored the specific pathology of migraine and corresponding compounds. A cerebrovascular smooth muscle spasmolytic activity experiment was carried out to verify the results of the bioinformatics analysis. ResultsTTNC exhibited its regulation activities in neuronal and non-neuronal aspects based on drugs attack to four subnetworks and cell specific networks, which explored the MoA of TTNC in comprehensive and refined perspectives. Compared to neuronal regulation, TTNC showed more significant attack score on non-neuronal biological function (smooth muscle and vessel). And TTNC compound clusters C1, C6 and C7, targeting non-neuronal function and cells, had larger group area than C10, C4 and C6 for neuronal function and cell, which implied that TTNC may mainly regulate the non-neuronal function, e.g., vessel smooth muscle contraction. Contraction of cerebrovascular smooth muscle of mice ex vivo confirmed the vasodilation activity of TTNC and active compounds from C1, C6, C9 (Emodin, Luteolin and Levistilide A). Literature mining confirmed the vasospasmodolytic activity and neuroprotective effect of TTNC. ConclusionsThe study found that TTNC may primarily alleviate non-neuronal functional disorders in migraine by relaxing cerebral vascular smooth muscle cell spasm to alleviate migraine. Integrating single-nucleus RNA sequencing data and network disturbance tools provides a new strategy for the pharmacological mechanism of multicomponent drugs through cell subtyping.

Glymphatic dysfunction in migraine mice model.

The glymphatic system is important for waste removal in the central nervous system. It removes soluble proteins and metabolic waste under the action of aquaporin-4 (AQP4) at the end of astrocytes. The glymphatic system plays a role in numerous neurological diseases; however, the relationship between migraine and the glymphatic system remains unclear. In this study, we explored the relationship between the glymphatic system and migraine using the nitroglycerin migraine model in C57/BL6mice. The glymphatic influx of cerebrospinal fluid tracer was reduced in mice in the migraine model, accompanied by decreased expression and impaired polarization of AQP4, thereby suggesting glymphatic dysfunction in migraine mice model. Then, further suppression of glymphatic function by TGN-020 (an AQP4 blocker) aggravated the migraine pathological changes in mice. The results indicated that glymphatic dysfunction may aggravate migraine pathology. Therefore, our findings revealed the potential role of the glymphatic system in migraine, providing possible targets for migraine prevention and treatment.

Migraine: Advances in the Pathogenesis and Treatment.

This article presents a comprehensive review on migraine, a prevalent neurological disorder characterized by chronic headaches, by focusing on their pathogenesis and treatment advances. By examining molecular markers and leveraging imaging techniques, the research identifies key mechanisms and triggers in migraine pathology, thereby improving our understanding of its pathophysiology. Special emphasis is given to the role of calcitonin gene-related peptide (CGRP) in migraine development. CGRP not only contributes to symptoms but also represents a promising therapeutic target, with inhibitors showing effectiveness in migraine management. The article further explores traditional medical treatments, scrutinizing the mechanisms, benefits, and limitations of commonly prescribed medications. This provides a segue into an analysis of emerging therapeutic strategies and their potential to enhance migraine management. Finally, the paper delves into neuromodulation as an innovative treatment modality. Clinical studies indicating its effectiveness in migraine management are reviewed, and the advantages and limitations of this technique are discussed. In summary, the article aims to enhance the understanding of migraine pathogenesis and present novel therapeutic possibilities that could revolutionize patient care.

CGRP, Migraine, and Brain MRI in CADASIL: A Pilot Study.

Migraine is associated with neuroimaging differences in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, it is unknown if migraine-related disability (MRD) or if calcitonin gene-related peptide (CGRP), a vasoactive peptide important in migraine pathology, have radiographic implications. The aims of this study were to identify whether MRD or interictal serum CGRP levels impacted neuroimaging findings for those with CADASIL. A cross-sectional analysis was performed. The primary outcomes were neuroimaging differences associated with MRD among those with migraine or interictal serum CGRP levels of those with and without migraine. MRD was defined by 2 migraine disability scales (Migraine Disability Assessment, Headache Impact Test-6). Retrospective brain magnetic resonance imaging was reviewed (average 1.7 ± 2.0y before enrollment). Rank-sum and χ 2 tests were used. Those with migraine (n=25, vs. n=14 without) were younger [median 49 (25 to 82)y vs. 60 (31 to 82)y, P <0.007], had fewer cerebral microbleeds (0 to 31 vs. 0 to 50, P =0.02) and less frequently had anterior temporal lobe T2 hyperintensities [68% (17/25) vs 100% (14/14), P =0.02]. MRD scale outcomes had no significant radiographic associations. Interictal serum CGRP did not differ (migraine: n=18, 27.0±9.6pg/mL vs. no migraine: n=10, 26.8±15.7pg/mL, P =0.965). Migraine may forestall microangiopathy in CADASIL, though possibly independent of severity as measured by MRD. Interictal serum CGRP did not differ in our cohort suggesting CGRP may not be vital to migraine pathophysiology in CADASIL. Larger studies are needed to account for age differences.

Assessment of Functional Characteristics of Small Arterioles and Capillaries Using an Intact Dura Mater Preparation

The dura mater, a protective layer surrounding the brain and spinal cord, plays a crucial role in maintaining homeostatic function of the central nervous system. The large arteries and veins of the dura mater are relatively sparse and have been extensively studied with respect to their contribution to pain sensation, with unclear and controversial contributions to headache and migraine pathology. Small arterioles and capillaries exhibit nearly ubiquitous coverage of the entire dura, yet their physiological and pathophysiological functions remain largely unexplored. Here, using ex vivo mouse dura, we examined the electrical (membrane potential recordings), Ca2+ signaling properties (GCaMP or Cal-520 AM imaging), and vasomotor behavior (pressurized dura vessels with diameter measurement) of these exquisitely small vessels. Furthermore, we show electrical and Ca2+ responses in smooth muscle and pericytes in response to calcitonin gene-related peptide (CGRP) receptor and transient receptor potential V1 (TRPV1) channel activation, which are two principal targets in headache and migraine pathology. Last, we highlight unique anatomical interactions between nerves and arterioles in the dura mater using immunostaining techniques. In conclusion, we hypothesize that microvessels consisting of arterioles and capillaries are a logical and unexplored region for studying homeostatic and pathological roles of the dura mater. Funding Provided by the Totman Medical Trust This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.