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1.
Int J Mol Sci ; 22(5)2021 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-33799975

RESUMO

Migraine is a common neurological disease that affects about 11% of the adult population. The disease is divided into two main clinical subtypes: migraine with aura and migraine without aura. According to the neurovascular theory of migraine, the activation of the trigeminovascular system (TGVS) and the release of numerous neuropeptides, including calcitonin gene-related peptide (CGRP) are involved in headache pathogenesis. TGVS can be activated by cortical spreading depression (CSD), a phenomenon responsible for the aura. The mechanism of CSD, stemming in part from aberrant interactions between neurons and glia have been studied in models of familial hemiplegic migraine (FHM), a rare monogenic form of migraine with aura. The present review focuses on those interactions, especially as seen in FHM type 1, a variant of the disease caused by a mutation in CACNA1A, which encodes the α1A subunit of the P/Q-type voltage-gated calcium channel.


Assuntos
Canais de Cálcio/metabolismo , Transtornos de Enxaqueca/etiologia , Neuroglia/patologia , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Cálcio/metabolismo , Canais de Cálcio/genética , Canais de Cálcio Tipo N/química , Canais de Cálcio Tipo N/genética , Canais de Cálcio Tipo N/metabolismo , Humanos , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/fisiopatologia , Mutação , Neuroglia/metabolismo
2.
J Med Chem ; 64(6): 3427-3438, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33715378

RESUMO

Inhibition of the pituitary adenylate cyclase 1 receptor (PAC1R) is a novel mechanism that could be used for abortive treatment of acute migraine. Our research began with comparative analysis of known PAC1R ligand scaffolds, PACAP38 and Maxadilan, which resulted in the selection of des(24-42) Maxadilan, 6, as a starting point. C-terminal modifications of 6 improved the peptide metabolic stability in vitro and in vivo. SAR investigations identified synergistic combinations of amino acid replacements that significantly increased the in vitro PAC1R inhibitory activity of the analogs to the pM IC90 range. Our modifications further enabled deletion of up to six residues without impacting potency, thus improving peptide ligand binding efficiency. Analogs 17 and 18 exhibited robust in vivo efficacy in the rat Maxadilan-induced increase in blood flow (MIIBF) pharmacodynamic model at 0.3 mg/kg subcutaneous dosing. The first cocrystal structure of a PAC1R antagonist peptide (18) with PAC1R extracellular domain is reported.


Assuntos
Circulação Sanguínea/efeitos dos fármacos , Peptídeos/química , Peptídeos/farmacologia , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/antagonistas & inibidores , Animais , Humanos , Proteínas de Insetos/farmacologia , Masculino , Camundongos , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/metabolismo , Transtornos de Enxaqueca/fisiopatologia , Simulação de Acoplamento Molecular , Peptídeos/farmacocinética , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/química , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Vasodilatadores/farmacologia
3.
Lancet ; 397(10283): 1496-1504, 2021 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-33773610

RESUMO

Migraine is a disabling neurological disorder, diagnosis of which is based on clinical criteria. A shortcoming of these criteria is that they do not fully capture the heterogeneity of migraine, including the underlying genetic and neurobiological factors. This complexity has generated momentum for biomarker research to improve disease characterisation and identify novel drug targets. In this Series paper, we present the progress that has been made in the search for biomarkers of migraine within genetics, provocation modelling, biochemistry, and neuroimaging research. Additionally, we outline challenges and future directions for each biomarker modality. We also discuss the advances made in combining and integrating data from multiple biomarker modalities. These efforts contribute to developing precision medicine that can be applied to future patients with migraine.


Assuntos
Transtornos de Enxaqueca/fisiopatologia , Biomarcadores/sangue , Marcadores Genéticos , Humanos , Transtornos de Enxaqueca/classificação , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/genética , Neuroimagem , Medicina de Precisão
4.
Clin Biomech (Bristol, Avon) ; 82: 105276, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33561677

RESUMO

BACKGROUND: Despite previous reports supporting cervical muscle weakness and altered motor control in migraine, the endurance under standardized submaximal loads has not been investigated. Therefore, this study aimed to assess the endurance and muscle activity of the cervical musculature during submaximal isometric contractions in women with migraine and those without headache. METHODS: Cervical muscle endurance tests were performed for flexors and extensors at 25%, 50%, and 75% of the output force during maximal isometric contraction using the Multi-Cervical Rehabilitation Unit with customized biofeedback. Initial values and relative rates of changes in root mean square and median frequency were calculated using cervical muscle superficial electromyography. FINDINGS: Women with chronic migraine presented significantly shorter flexor endurance time in all load tests than controls (25%, P = .001, 50%, P = .005; 75%, P = .013), while episodic migraine only differed from controls at 75% (P = .018). The frequency of neck pain and/or pain referred to the head after the endurance test was up 12% in the control group, 40% in the episodic migraine group and 68% of the chronic migraine group. Few differences between groups were observed in the electromyographic variables and none of them was related to a worse performance in the endurance tests. INTERPRETATION: Cervical flexor endurance was reduced in women with chronic migraine when independent of the load, whereas it was reduced to 75% of the maximal force in those with episodic migraine. No difference in the electromyographic variables could be related to this reduced flexor endurance. Also, no differences were detected in extensors endurance.


Assuntos
Vértebras Cervicais/fisiopatologia , Eletromiografia , Transtornos de Enxaqueca/fisiopatologia , Fadiga Muscular , Músculos do Pescoço/fisiopatologia , Adulto , Feminino , Humanos , Contração Isométrica
5.
Lancet Neurol ; 20(4): 304-315, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33600767

RESUMO

The term menstrual migraine refers to migraine that is associated with menstruation by more than chance, but it does not define pathophysiology. Menstrual migraine affects about 20-25% of female migraineurs in the general population, and 22-70% of patients presenting to headache clinics. In women diagnosed with menstrual migraine, perimenstrual migraine attacks are associated with substantially greater disability than their non-menstrual attacks. Loose interpretation of diagnostic criteria has led to conflicting results in studies on prevalence figures, clinical characteristics, and response to treatment. Importantly, clinical trials often do not distinguish between perimenstrual attacks in women diagnosed with menstrual migraine and attacks associated with menstruation by chance. Two pathophysiological mechanisms have been identified: oestrogen withdrawal and prostaglandin release. Although management strategies targeting these mechanisms might be effective, the evidence is not robust. Given how common and debilitating this distinct condition is, more research investment is needed to expand understanding of its pathophysiology and to develop more effective treatment strategies.


Assuntos
Menstruação , Transtornos de Enxaqueca/etiologia , Transtornos de Enxaqueca/fisiopatologia , Adulto , Feminino , Humanos
6.
Neurología (Barc., Ed. impr.) ; 36(1): 24-28, ene.-feb. 2021. tab
Artigo em Espanhol | IBECS | ID: ibc-200442

RESUMO

INTRODUCCIÓN: El pensamiento catastrófico (PC) hace referencia a un tipo de respuesta cognitiva y emocional negativa ante el dolor y se considera que contribuye a su cronificación. Pretendemos evaluar su presencia en una población de pacientes migrañosos. MÉTODOS: Pacientes atendidos en una unidad de cefaleas de un hospital terciario (enero-junio de 2015). Se recogieron datos sociodemográficos y características de la migraña. Se midió el PC mediante la versión española de la Pain Catastrophizing Scale (PCS). Se comparó la presencia de PC en pacientes con migraña crónica y episódica y su correlación con las medidas de impacto (Escala HIT-6), de depresión y ansiedad (Escala Hospitalaria de Ansiedad y Depresión [HADS]) y la presencia de uso excesivo de medicación. RESULTADOS: Se incluyeron 96 pacientes (16 varones y 80 mujeres). Sesenta y siete (69,8%) con migraña crónica y 29 (30,2%) con migraña episódica. El 85,4% presentó un impacto de la migraña al menos moderado (HIT-6 ≥ 56), el 24% superó el punto de corte para la ansiedad y el 9,4% para depresión. El 34,4% de la muestra superó el punto de corte de la PCS. En el grupo de pacientes con PC, mayor puntuación en la escala HADS-ansiedad (p < 0,001), HADS-depresión (p < 0,001) y HIT-6 (p < 0,001). CONCLUSIONES: El PC es frecuente en pacientes con migraña. Se relaciona con la severidad de la misma y la asociación a ansiedad y depresión. Su presencia parece no incrementar la cronificación de la migraña ni el uso excesivo de medicación sintomática


INTRODUCTION: Catastrophic thought refers to a negative cognitive and emotional response to pain, and is thought to contribute to pain chronification. We aimed to evaluate pain catastrophising PC in a population of patients with migraine. METHODS: We collected sociodemographic data and clinical data on migraine from patients attended at a tertiary hospital headache unit between January and June 2015. PC was measured with the Spanish-language version of the Pain Catastrophizing Scale (PCS). We compared presence of PC in patients with episodic and chronic migraine, and its correlation with clinical impact (measured by the Headache Impact Test-6 [HIT-6] scale), comorbid depression and anxiety (measured with the Hospital Anxiety and Depression Scale [HADS]), and the presence of medication overuse. RESULTS: The study included 96 patients (16 men and 80 women); 67 (69.8%) were diagnosed with chronic migraine and 29 (30.2%) with episodic migraine. Migraine impact was at least moderate (HIT-6 ≥ 56) in 85.4% of cases, and 24% exceeded the cut-off point for anxiety and 9.4% for depression. A total of 34.4% presented PC. Patients with chronic migraine scored higher than those with episodic symptoms on the HADS for anxiety (P < .001) and depression (P < .001) and on the HIT-6 (P < .001). CONCLUSIONS: PC is common among patients with migraine. It is related to migraine severity and to comorbid anxiety and depression. PC does not appear to increase the likelihood of migraine chronification or medication overuse


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Catastrofização/psicologia , Transtornos de Enxaqueca/psicologia , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença , Catastrofização/fisiopatologia , Transtornos de Enxaqueca/fisiopatologia , Depressão/fisiopatologia , Depressão/psicologia , Ansiedade/fisiopatologia , Ansiedade/psicologia , Fatores de Risco
7.
Am J Med ; 134(6): 756-762.e5, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33444588

RESUMO

BACKGROUND: There is interest in whether supplements, including vitamin D and marine omega-3 (n-3) fatty acids, may be effective migraine prophylaxis. However, few studies have evaluated whether vitamin D or n-3 fatty acid supplementation may reduce migraine frequency or severity. METHODS: Participants in the VITamin D and OmegA-3 TriaL (VITAL) were assigned to vitamin D3 (2000 IU/d) or marine n-3 fatty acid (1 g/d) supplementation in a 2-by-2 factorial design. Lifetime history of migraine was assessed a median of 4.6 years after the start of the trial. Individuals were asked to self-report changes in migraine frequency (no change, more frequent, or less frequent) and severity (no change, more severe, less severe) in the past 5 years. We used χ2 tests to compare proportions of individuals reporting changes in migraine frequency and severity between active and placebo groups. RESULTS: Among the 25,871 participants in VITAL, 1032 participants had a history of probable migraine and provided information on changes in migraine frequency and severity. The percentage of individuals reporting decreases in migraine frequency did not differ between active (69.0%) and placebo vitamin D (68.4%) (P value = 0.54) or between active (67.8%) and placebo n-3 fatty acid (69.6%) (P value = 0.82). Similarly, the percentage of individuals reporting decreases in migraine severity did not differ between active (64.1%) and placebo vitamin D (65.0%) (P value = 0.86) or between active (64.5%) and placebo n-3 fatty acid (64.5%) (P value = 0.96). CONCLUSIONS: Neither vitamin D nor marine n-3 fatty acid supplementation, compared to placebo, affected migraine frequency or severity among middle-aged or older adults.


Assuntos
Ácidos Graxos Ômega-3/farmacologia , Transtornos de Enxaqueca/tratamento farmacológico , Vitamina D/farmacologia , Idoso , Método Duplo-Cego , Ácidos Graxos Ômega-3/uso terapêutico , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/fisiopatologia , Dor/tratamento farmacológico , Dor/prevenção & controle , Inquéritos e Questionários , Vitamina D/uso terapêutico
8.
Expert Opin Drug Metab Toxicol ; 17(2): 179-199, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33470852

RESUMO

Introduction: In addition to serotonin (5-hydroxytryptamine; 5-HT) and other (neuro)mediators, the role of neuropeptides in migraine pathophysiology is relevant. Indeed, while some molecules interfering with calcitonin gene-related peptide (CGRP) transmission have recently been approved for clinical antimigraine use, other neuropeptides with translational use are in the pipeline. Among others, hypothalamic neuropeptides such as pituitary adenylate cyclase-activating peptide (PACAP), oxytocin (OT), and orexins stand out as potential novel targets to treat this neurovascular disorder. Areas covered: Based on the aforementioned findings, the present review: (i) summarizes the current knowledge on the role of the above neuropeptides in the trigeminovascular system, and migraine pathophysiology; and (ii) discusses some issues related with the mechanisms of action and side effects concerns that could be elicited when targeting the CGRPergic, PACAPergic, oxytocinergic and orexinergic systems. Expert opinion: Specific antimigraine pharmacotherapies have evolved from the enhancement of serotonergic 5-HT1B/1D/1F transmission to the use of compounds interacting with neuropeptidergic systems. Canonically, neuropeptides cause an array of complex intracellular mechanisms that, after modifying neuronal and/or vascular transmission, result in antimigraine action and also potential side effects. Furthermore, due to the chemical nature of some molecules targeting the above neuropeptidergic transmission (e.g., monoclonal antibodies, peptides), there are some limiting pharmacokinetics issues.


Assuntos
Transtornos de Enxaqueca/tratamento farmacológico , Neuropeptídeos/metabolismo , Animais , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Humanos , Transtornos de Enxaqueca/fisiopatologia , Orexinas/metabolismo , Ocitocina/metabolismo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Serotonina/metabolismo
9.
J Ethnopharmacol ; 265: 113326, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32877718

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Migraines have become a major threat to human health, as they significantly affect human health and quality of life due to a high prevalence rate, attack rate and pain intensity. Aromatherapy, with its comfortable and pleasant natural characteristics and rapid and efficient characteristics, is widely favored by patients in the folk. Chinese folk also have the application history and related records of aromatic plants in the treatment of migraine. AIM OF THE STUDY: This study was conducted to review the pathogenesis of migraine, the application of plant essential oils in the treatment of migraine, and further explore the material basis and mechanism of action of plant essential oils against migraine. MATERIALS AND METHODS: Search the electronic literature of essential oils with anti-migraine effect in Google Scholar, PubMed and China National Knowledge Infrastructure, and further search the research situation of the monomer components of essential oils in migraine, inflammation, pain and other aspects. RESULTS: studies show that there are 10 types of plant essential oils that could relieve migraine symptoms, and that 16 monomers may play a role in migraine treatment by effectively inhibiting neurogenic inflammation, hyperalgesia and balancing vasorelaxation. CONCLUSION: Aromatic plant essential oils can relieve migraine effectively, these findings can be used as an important part of the development of anti-migraine drugs.


Assuntos
Aromaterapia/métodos , Transtornos de Enxaqueca/terapia , Óleos Voláteis/administração & dosagem , Animais , Humanos , Transtornos de Enxaqueca/fisiopatologia , Óleos Voláteis/farmacologia , Óleos Vegetais/administração & dosagem , Óleos Vegetais/farmacologia , Qualidade de Vida
10.
Ann Neurol ; 89(3): 459-473, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33314303

RESUMO

OBJECTIVE: The purpose of this study was to investigate the significance of circulating micro RNAs (miRNAs) in the pathogenesis of reversible cerebral vasoconstriction syndrome (RCVS). METHODS: We prospectively recruited 3 independent cohorts of patients with RCVS and age-matched and sex-matched controls in a single medical center. Next-generation small RNA sequencing followed by quantitative polymerase chain reaction (PCR) was used to identify and validate differentially expressed miRNAs, which was cross-validated in migraine patients in ictal stage or interictal stage. Computational analysis was used to predict the target genes of miRNAs, followed by in vitro functional analysis. RESULTS: We identified a panel of miRNAs including miR-130a-3p, miR-130b-3p, let-7a-5p, let-7b-5p, and let-7f-5p that well differentiated patients with RCVS from controls (area under the receiver operating characteristics curve [AUC] was 0.906, 0.890, and 0.867 in the 3 cohorts, respectively). The abundance of let-7a-5p, let-7b-5p, and let-7f-5p, but not miR-130a-3p nor miR-130b-3p, was significantly higher in patients with ictal migraine compared with that of controls and patients with interictal migraine. Target prediction and pathway enrichment analysis suggested that the transforming growth factor-ß signaling pathway and endothelin-1 responsible for vasomotor control might link these miRNAs to RCVS pathogenesis, which was confirmed in vitro by transfecting miRNAs mimics or incubating the patients' cerebrospinal fluid (CSF) in 3 different vascular endothelial cells. Moreover, miR-130a-3p was associated with imaging-proven disruption of the blood-brain barrier (BBB) in patients with RCVS and its overexpression led to reduced transendothelial electrical resistance (ie, increased permeability) in in vitro human BBB model. INTERPRETATION: We identified the circulating miRNA signatures associated with RCVS, which may be functionally linked to its headache, BBB integrity, and vasomotor function. ANN NEUROL 2021;89:459-473.


Assuntos
Barreira Hematoencefálica/fisiopatologia , Transtornos Cerebrovasculares/genética , MicroRNA Circulante/sangue , Células Endoteliais , MicroRNAs/sangue , Vasoconstrição/genética , Adulto , Permeabilidade Capilar , Estudos de Casos e Controles , Transtornos Cerebrovasculares/sangue , Transtornos Cerebrovasculares/fisiopatologia , MicroRNA Circulante/genética , Simulação por Computador , Impedância Elétrica , Endotelina-1/genética , Endotelina-1/metabolismo , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Células Endoteliais da Veia Umbilical Humana , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/sangue , Transtornos de Enxaqueca/genética , Transtornos de Enxaqueca/fisiopatologia , Reprodutibilidade dos Testes , Análise de Sequência de RNA , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Sistema Vasomotor/fisiopatologia
11.
Am J Chin Med ; 48(8): 1731-1748, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33308095

RESUMO

Migraine is a recurrent disease with complex pathogenesis and is difficult to cure. At present, commercially available western migraine drugs are prone to generate side effects while treating the disease. Traditional Chinese medicine (TCM) avoids side effects via treatment with the principles of "treating both symptoms and root causes", "overall adjustment", and "treatment based on syndrome differentiation". Three strategies of drug treatment were developed based on the syndromes, i.e., removing stasis, calming liver Yang, and reinforcing deficiency. Prescriptions of removing stasis mostly contain Chuanxiong rhizome (Chuan Xiong) to remove blood stasis by promoting blood circulation and improve properties of hemorheology, and Da Chuan Xiong Formula (DCXF) is a traditional prescription widely used in clinical practice. Prescriptions of calming liver Yang usually take Ramulus Uncariae cum Uncis (Gou Teng) as the main herb, which can calm the liver Yang via improving vasomotor function, and Tian Ma Gou Teng Decoction (TMGTD) is the representative drug. For reinforcing deficiency, Chinese doctors frequently utilize Angelica Sinensis (Dang Gui) and Astragali Radix (Huang Qi) to nourish blood and Qi in order to improve the weak state of human body; Dang Gui Bu Xue Decoction (DGBXD) is the commonly used prescription. These strategies not only treat the symptoms of diseases but also their root causes, and with the features of multiple targets, in multiple ways. Therefore, TCM prescriptions have obvious advantages in the treatment of chronic diseases such as migraine. In this review, we provided an overview of the pathogenesis of migraine and the function of representative TCM preparations in therapy of migraine as well as the mechanism of action according to effective researches, in order to provide reference and clue for further researches.


Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Medicina Tradicional Chinesa/tendências , Transtornos de Enxaqueca/tratamento farmacológico , Fitoterapia , Circulação Sanguínea , Humanos , Transtornos de Enxaqueca/etiologia , Transtornos de Enxaqueca/fisiopatologia
12.
J Headache Pain ; 21(1): 131, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33167864

RESUMO

BACKGROUND: Migraine occurs 2-3 times more often in females than in males and is in many females associated with the onset of menstruation. The steroid hormone, 17ß-estradiol (estrogen, E2), exerts its effects by binding and activating several estrogen receptors (ERs). Calcitonin gene-related peptide (CGRP) has a strong position in migraine pathophysiology, and interaction with CGRP has resulted in several successful drugs for acute and prophylactic treatment of migraine, effective in all age groups and in both sexes. METHODS: Immunohistochemistry was used for detection and localization of proteins, release of CGRP and PACAP investigated by ELISA and myography/perfusion arteriography was performed on rat and human arterial segments. RESULTS: ERα was found throughout the whole brain, and in several migraine related structures. ERß was mainly found in the hippocampus and the cerebellum. In trigeminal ganglion (TG), ERα was found in the nuclei of neurons; these neurons expressed CGRP or the CGRP receptor in the cytoplasm. G-protein ER (GPER) was observed in the cell membrane and cytoplasm in most TG neurons. We compared TG from males and females, and females expressed more ER receptors. For neuropeptide release, the only observable difference was a baseline CGRP release being higher in the pro-estrous state as compared to estrous state. In the middle cerebral artery (MCA), we observed similar dilatory ER-responses between males and females, except for vasodilatory ERß which we observed only in female arteries. CONCLUSION: These data reveal significant differences in ER receptor expression between male and female rats. This contrasts to CGRP and PACAP release where we did not observe discernable difference between the sexes. Together, this points to a hypothesis where estrogen could have a modulatory role on the trigeminal neuron function in general rather than on the acute CGRP release mechanisms and vasomotor responses.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Sistema Nervoso Central/metabolismo , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Gânglio Trigeminal/metabolismo , Animais , Feminino , Humanos , Masculino , Transtornos de Enxaqueca/fisiopatologia , Neurônios/metabolismo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Peptídeo Relacionado com o Gene de Calcitonina/metabolismo , Transdução de Sinais
13.
J Headache Pain ; 21(1): 115, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32972360

RESUMO

BACKGROUND: Since the declaration COVID-19 as a pandemic, healthcare systems around the world have faced a huge challenge in managing patients with chronic diseases. Patients with migraine were specifically vulnerable to inadequate medical care. We aimed to investigate the "real-world" impact of COVID-19 pandemic on migraine patients, and to identify risk factors for poor outcome. METHODS: We administered an online, self-reported survey that included demographic, migraine-related, COVID-19-specific and overall psychosocial variables between July 15 and July 30, 2020. We recruited a sample of patients with migraine from headache clinic registry and via social media to complete an anonymous survey. Outcomes included demographic variables, change in migraine frequency and severity during the lockdown period, communication with treating physician, compliance to migraine treatment, difficulty in getting medications, medication overuse, symptoms of anxiety and/or depression, sleep and eating habits disturbance, screen time exposure, work during pandemic, use of traditional medicine, effect of Botox injection cancellation, and overall worries and concerns during pandemic. RESULTS: A total of 1018 patients completed the survey. Of the respondents, 859 (84.3%) were females; 733 (71.9%) were aged 20 to 40 years, 630 (61.8%) were married, and 466 (45.7%) reported working during the pandemic. In comparison to pre-pandemic period, 607 respondents (59.6%) reported increase in migraine frequency, 163 (16%) reported decrease in frequency, and 105 (10.3%) transformed to chronic migraine. Severity was reported to increase by 653 (64.1%) respondents. The majority of respondents; 626 (61.5%) did not communicate with their neurologists, 477 (46.9%) reported compliance to treatment, and 597 (58.7%) reported overuse of analgesics. Botox injections cancellation had a negative impact on 150 respondents (66.1%) from those receiving it. Forty-one respondents (4%) were infected with COVID-19; 26 (63.4%) reported worsening of their headaches amid infection period. Sleep disturbance was reported by 794 (78.1%) of respondents, and 809 (79.5%) reported having symptoms of anxiety and/or depression. CONCLUSIONS AND RELEVANCE: COVID-19 pandemic had an overall negative impact on patients with migraine. Several risk factors for poor outcome were identified. Long-term strategies should be validated and implemented to deliver quality care for patients with migraine, with emphasis on psychosocial well-being.


Assuntos
Infecções por Coronavirus/epidemiologia , Transtornos de Enxaqueca/fisiopatologia , Pneumonia Viral/epidemiologia , Uso Excessivo de Medicamentos Prescritos/estatística & dados numéricos , Adulto , Analgésicos/uso terapêutico , Ansiedade/psicologia , Betacoronavirus , Toxinas Botulínicas Tipo A/uso terapêutico , Comunicação , Depressão/psicologia , Feminino , Acesso aos Serviços de Saúde , Humanos , Internet , Kuweit/epidemiologia , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/prevenção & controle , Transtornos de Enxaqueca/psicologia , Fármacos Neuromusculares/uso terapêutico , Pandemias , Relações Médico-Paciente , Fatores de Risco , Sono , Distúrbios do Início e da Manutenção do Sono/fisiopatologia , Distúrbios do Início e da Manutenção do Sono/psicologia , Inquéritos e Questionários , Adulto Jovem
14.
Plast Reconstr Surg ; 146(2): 187e-195e, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32740592

RESUMO

BACKGROUND: Recent clinical experience with migraine surgery has demonstrated both the safety and the efficacy of operative decompression of the peripheral nerves in the face, head, and neck for the alleviation of migraine symptoms. Because of the perceived novelty of these procedures, and the paranoia surrounding a theoretical loss of clinical territory, neurologists have condemned the field of migraine surgery. The Patient Safety Subcommittee of the American Society of Plastic Surgeons ventured to investigate the published safety track record of migraine surgery in the existing body of literature. METHODS: A comprehensive review of the relevant published literature was performed. The relevant databases and literature libraries were reviewed from the date of their inception through early 2018. These articles were reviewed and their findings analyzed. RESULTS: Thirty-nine published articles were found that demonstrated a substantial, extensively replicated body of data that demonstrate a significant reduction in migraine headache symptoms and frequency (even complete elimination of headache pain) following trigger-site surgery. CONCLUSIONS: Migraine surgery is a valid method of treatment for migraine sufferers when performed by experienced plastic surgeons following a methodical protocol. These operations are associated with a high level of safety. The safety and efficacy of migraine surgery should be recognized by plastic surgeons, insurance companies, and the neurology societies.


Assuntos
Descompressão Cirúrgica/métodos , Transtornos de Enxaqueca/cirurgia , Procedimentos Neurocirúrgicos/métodos , Nervos Periféricos/fisiopatologia , Descompressão Cirúrgica/efeitos adversos , Humanos , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/fisiopatologia , Procedimentos Neurocirúrgicos/efeitos adversos , Medição da Dor , Resultado do Tratamento
15.
J Headache Pain ; 21(1): 95, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32746775

RESUMO

BACKGROUND: We performed a post hoc, subgroup analysis of a phase 3, randomized, double-blind, placebo-controlled study of erenumab for prevention of episodic migraine (STRIVE) to determine the efficacy and safety of erenumab in women with self-reported menstrual migraine. METHODS: Patients received placebo, erenumab 70 mg, or erenumab 140 mg subcutaneously once monthly during the 6-month double-blind treatment phase of STRIVE. Women who reported history of menstrual migraine and who were ≤ 50 years old were included in the analysis. Endpoints were change from baseline in monthly migraine days (MMD) and monthly acute migraine-specific medication days (MSMD; among patients who took acute migraine-specific medications at baseline), proportion of patients achieving ≥ 50% reduction from baseline in MMD, and incidence of adverse events. RESULTS: Among 814 women enrolled in STRIVE, 232 (28.5%) reported a history of menstrual migraine and were ≤ 50 years old. Of the 232 patients, 214 (92%) had a baseline MMD > 5, suggesting a high proportion of women with attacks outside of the 5-day perimenstrual window (2 days before and 3 days after the start of menstruation). Information on "migraine days" includes (and does not discriminate between) perimenstrual and intermenstrual migraine attacks. Between-group differences from placebo over months 4-6 for erenumab 70 mg and 140 mg were - 1.8 (P = 0.001) and - 2.1 (P < 0.001) days for MMD and - 1.6 (P = 0.002) and - 2.4 (P < 0.001) days for acute MSMD, respectively. The odds of having a ≥ 50% reduction from baseline in MMD over months 4-6 were 2.2 (P = 0.024) and 2.8 (P = 0.002) times greater for erenumab 70 mg and 140 mg, respectively, than for placebo. Erenumab had an overall safety profile comparable to placebo. CONCLUSION: Data from this subgroup analysis of women with menstrual migraine are consistent with data from the overall STRIVE episodic migraine population, supporting the efficacy and safety of erenumab in women who experience menstrual migraine. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02456740. Registered 28 May 2015.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/uso terapêutico , Ciclo Menstrual/efeitos dos fármacos , Transtornos de Enxaqueca/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/farmacologia , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/farmacologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Ciclo Menstrual/fisiologia , Pessoa de Meia-Idade , Transtornos de Enxaqueca/fisiopatologia , Autorrelato , Resultado do Tratamento , Adulto Jovem
17.
J Headache Pain ; 21(1): 90, 2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32664898

RESUMO

BACKGROUND: According to the International Classification of Headache Disorders 3, post-traumatic headache (PTH) attributed to traumatic brain injury (TBI) is a secondary headache reported to have developed within 7 days from head injury, regaining consciousness following the head injury, or discontinuation of medication(s) impairing the ability to sense or report headache following the head injury. It is one of the most common secondary headache disorders, and it is defined as persistent when it lasts more than 3 months. MAIN BODY: Currently, due to the high prevalence of this disorder, several preclinical studies have been conducted using different animal models of mild TBI to reproduce conditions that engender PTH. Despite representing a simplification of a complex disorder and displaying different limitations concerning the human condition, animal models are still a mainstay to study in vivo the mechanisms of PTH and have provided valuable insight into the pathophysiology and possible treatment strategies. Different models reproduce different types of trauma and have been ideated in order to ensure maximal proximity to the human condition and optimal experimental reproducibility. CONCLUSION: At present, despite its high prevalence, PTH is not entirely understood, and the differential contribution of pathophysiological mechanisms, also observed in other conditions like migraine, has to be clarified. Although facing limitations, animal models are needed to improve understanding of PTH. The knowledge of currently available models is necessary to all researchers who want to investigate PTH and contribute to unravel its mechanisms.


Assuntos
Concussão Encefálica/fisiopatologia , Modelos Animais de Doenças , Transtornos de Enxaqueca/fisiopatologia , Cefaleia Pós-Traumática/fisiopatologia , Animais , Concussão Encefálica/complicações , Concussão Encefálica/diagnóstico , Humanos , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/etiologia , Cefaleia Pós-Traumática/diagnóstico , Cefaleia Pós-Traumática/etiologia , Prevalência , Reprodutibilidade dos Testes
18.
J Headache Pain ; 21(1): 71, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32522164

RESUMO

Migraine is a leading cause of disability worldwide, but it is still underdiagnosed and undertreated. Research on the pathophysiology of this neurological disease led to the discovery that calcitonin gene-related peptide (CGRP) is a key neuropeptide involved in pain signaling during a migraine attack. CGRP-mediated neuronal sensitization and glutamate-based second- and third-order neuronal signaling may be an important component involved in migraine pain. The activation of several serotonergic receptor subtypes can block the release of CGRP, other neuropeptides, and neurotransmitters, and can relieve the symptoms of migraine. Triptans were the first therapeutics developed for the treatment of migraine, working through serotonin 5-HT1B/1D receptors. The discovery that the serotonin 1F (5-HT1F) receptor was expressed in the human trigeminal ganglion suggested that this receptor subtype may have a role in the treatment of migraine. The 5-HT1F receptor is found on terminals and cell bodies of trigeminal ganglion neurons and can modulate the release of CGRP from these nerves. Unlike 5-HT1B receptors, the activation of 5-HT1F receptors does not cause vasoconstriction.The potency of different serotonergic agonists towards 5-HT1F was correlated in an animal model of migraine (dural plasma protein extravasation model) leading to the development of lasmiditan. Lasmiditan is a newly approved acute treatment for migraine in the United States and is a lipophilic, highly selective 5-HT1F agonist that can cross the blood-brain barrier and act at peripheral nervous system (PNS) and central nervous system (CNS) sites.Lasmiditan activation of CNS-located 5-HT1F receptors (e.g., in the trigeminal nucleus caudalis) could potentially block the release of CGRP and the neurotransmitter glutamate, thus preventing and possibly reversing the development of central sensitization. Activation of 5-HT1F receptors in the thalamus can block secondary central sensitization of this region, which is associated with progression of migraine and extracephalic cutaneous allodynia. The 5-HT1F receptors are also elements of descending pain modulation, presenting another site where lasmiditan may alleviate migraine. There is emerging evidence that mitochondrial dysfunction might be implicated in the pathophysiology of migraine, and that 5-HT1F receptors can promote mitochondrial biogenesis. While the exact mechanism is unknown, evidence suggests that lasmiditan can alleviate migraine through 5-HT1F agonist activity that leads to inhibition of neuropeptide and neurotransmitter release and inhibition of PNS trigeminovascular and CNS pain signaling pathways.


Assuntos
Benzamidas/farmacologia , Transtornos de Enxaqueca/fisiopatologia , Piperidinas/farmacologia , Piridinas/farmacologia , Receptores de Serotonina , Agonistas do Receptor de Serotonina/farmacologia , Animais , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Humanos , Neurônios/metabolismo , Gânglio Trigeminal/metabolismo , Gânglio Trigeminal/fisiopatologia , Triptaminas , Vasoconstrição/efeitos dos fármacos
19.
J Headache Pain ; 21(1): 72, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32522232

RESUMO

BACKGROUND: Vestibular migraine has recently been recognized as a novel subtype of migraine. However, the mechanism that relate vestibular symptoms to migraine had not been well elucidated. Thus, the present study investigated vestibular dysfunction in a rat model of chronic migraine (CM), and to dissect potential mechanisms between migraine and vertigo. METHODS: Rats subjected to recurrent intermittent administration of nitroglycerin (NTG) were used as the CM model. Migraine- and vestibular-related behaviors were analyzed. Immunofluorescent analyses and quantitative real-time polymerase chain reaction were employed to detect expressions of c-fos and calcitonin gene-related peptide (CGRP) in the trigeminal nucleus caudalis (TNC) and vestibular nucleus (VN). Morphological changes of vestibular afferent terminals was determined under transmission electron microscopy. FluoroGold (FG) and CTB-555 were selected as retrograde tracers and injected into the VN and TNC, respectively. Lentiviral vectors comprising CGRP short hairpin RNA (LV-CGRP) was injected into the trigeminal ganglion. RESULTS: CM led to persistent thermal hyperalgesia, spontaneous facial pain, and prominent vestibular dysfunction, accompanied by the upregulation of c-fos labeling neurons and CGRP immunoreactivity in the TNC (c-fos: vehicle vs. CM = 2.9 ± 0.6 vs. 45.5 ± 3.4; CGRP OD: vehicle vs. CM = 0.1 ± 0.0 vs. 0.2 ± 0.0) and VN (c-fos: vehicle vs. CM = 2.3 ± 0.8 vs. 54.0 ± 2.1; CGRP mRNA: vehicle vs. CM = 1.0 ± 0.1 vs. 2.4 ± 0.1). Furthermore, FG-positive neurons was accumulated in the superficial layer of the TNC, and the number of c-fos+/FG+ neurons were significantly increased in rats with CM compared to the vehicle group (vehicle vs. CM = 25.3 ± 2.2 vs. 83.9 ± 3.0). Meanwhile, CTB-555+ neurons dispersed throughout the VN. The structure of vestibular afferent terminals was less pronounced after CM compared with the peripheral vestibular dysfunction model. In vivo knockdown of CGRP in the trigeminal ganglion significantly reduced the number of c-fos labeling neurons (LV-CGRP vs. LV-NC = 9.9 ± 3.0 vs. 60.0 ± 4.5) and CGRP mRNA (LV-CGRP vs. LV-NC = 1.0 ± 0.1 vs. 2.1 ± 0.2) in the VN, further attenuating vestibular dysfunction after CM. CONCLUSIONS: These data demonstrates the possibility of sensitization of vestibular nucleus neurons to impair vestibular function after CM, and anti-CGRP treatment to restore vestibular dysfunction in patients with CM.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Transtornos de Enxaqueca/fisiopatologia , Núcleos Vestibulares/metabolismo , Animais , Hiperalgesia/metabolismo , Masculino , Nitroglicerina/farmacologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Núcleo Inferior Caudal do Nervo Trigêmeo/metabolismo , Gânglio Trigeminal/metabolismo
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