CGRP physiology, pharmacology, and therapeutic targets: migraine and beyond

Physiological Reviews, Journal Year: 2022, Volume and Issue: 103(2), P. 1565 - 1644

Published: Dec. 1, 2022

Calcitonin gene-related peptide (CGRP) is a neuropeptide with diverse physiological functions. Its two isoforms (α and β) are widely expressed throughout the body in sensory neurons as well other cell types, such motor neuroendocrine cells. CGRP acts via at least G protein-coupled receptors that form unusual complexes receptor activity-modifying proteins. These AMY

Language: Английский

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Role of Estrogens in Menstrual Migraine

Cells, Journal Year: 2022, Volume and Issue: 11(8), P. 1355 - 1355

Published: April 15, 2022

Migraine is a major neurological disorder affecting one in nine adults worldwide with significant impact on health care and socioeconomic systems. more prevalent women than men, 17% of all meeting the diagnostic criteria for migraine. In women, frequency migraine attacks shows variations over menstrual cycle pregnancy, use combined hormonal contraception (CHC) or hormone replacement therapy (HRT) can unveil modify disease. general population, 18–25% female migraineurs display association their headache. Here we present an overview evidence supporting role reproductive hormones, particular estrogens, pathophysiology We also analyze efficacy safety prescribing exogenous estrogens as potential treatment menstrual-related Finally, point to controversial issues future research areas field hormones

Language: Английский

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Sex and gender differences in migraines: a narrative review

Neurological Sciences, Journal Year: 2022, Volume and Issue: 43(9), P. 5729 - 5734

Published: June 8, 2022

Abstract Introduction Gender medicine is a new medical approach aimed at the study of differences between women and men in terms prevention, diagnosis, outcome all diseases. Migraines are among these. They represent most common neurological illness; they prevalent adults 20 50 years age three to four times more frequent woman than men. Affecting people working age, migraines problem that strongly impacts psychophysical health productivity workers, regardless specific job task have. Methods A narrative review was performed, searching for relevant articles describing gender suffering from migraines, particularly workers. Results Migraine global prevalence 20.7% 9.7% whereas Italy 32.9% only 13.0% This difference partly explained by hormonal differences, as well brain structure, genetic polymorphisms neuronal pathways. Sex may also play role progression episodic chronic migraine. In mostly associated with strenuous physical work men, whilst triggered night shifts, lack sleep, or irregular sleep patterns women. Conclusions To this day, reasons sex/gender disparity migraine still obscure. However, particular, have negative impact on lives individuals affected disease, but which family cares activity often superimposed. prevention strategies should be planned workers through occupational physician.

Language: Английский

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Neural Functions of Hypothalamic Oxytocin and its Regulation

ASN NEURO, Journal Year: 2022, Volume and Issue: 14, P. 175909142211007 - 175909142211007

Published: Jan. 1, 2022

Oxytocin (OT), a nonapeptide, has variety of functions. Despite extensive studies on OT over past decades, our understanding its neural functions and their regulation remains incomplete. is mainly produced in neurons the supraoptic nucleus (SON), paraventricular (PVN) accessory nuclei between SON PVN. exerts neuromodulatory effects brain spinal cord. While magnocellular PVN innervate pituitary forebrain regions, parvocellular brainstem cord, two sets have close interactions histologically functionally. expression occurs at early life to promote mental physical development, while subsequent decrease later stage accompanies aging diseases. Adaptive changes this system, however, take place under different conditions upon maturation release machinery. can modulate social recognition behaviors, learning memory, emotion, reward, other higher also regulates eating drinking, sleep wakefulness, nociception analgesia, sexual behavior, parturition, lactation instinctive behaviors. autonomic nervous somatic specialized senses. Notably, modulatory same function conditions. Such divergence may derive from connections, receptor gene dimorphism methylation, complex with hormones. In review, underlying mechanisms as well perspectives clinical usage are presented.

Language: Английский

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Sex Hormones and Calcitonin Gene–Related Peptide in Women With Migraine

Neurology, Journal Year: 2023, Volume and Issue: 100(17)

Published: Feb. 22, 2023

Sex hormones may modulate calcitonin gene-related peptide (CGRP) release in the trigeminovascular system. We studied CGRP concentrations plasma and tear fluid female participants with episodic migraine (EM) a regular menstrual cycle (RMC), EM combined oral contraception (COC), postmenopause. For control, we analyzed 3 corresponding groups of age-matched without EM.Participants an RMC had 2 visits: during menstruation on day ± periovulatory period 13 2. Participants COC were examined at 4 hormone-free interval (HFI) between days 7 14 hormone intake (HI). Postmenopausal assessed once random time point. Plasma samples collected each visit for determination levels ELISA.A total 180 (n = 30 per group) completed study. showed statistically significantly higher compared (plasma: 5.95 pg/mL [IQR 4.37-10.44] vs 4.61 2.83-6.92], p 0.020 [Mann-Whitney U test]; fluid: 1.20 ng/mL 0.36-2.52] 0.4 0.14-1.22], 0.005 test]). In contrast, postmenopause similar control groups. RMC, but not under (p 0.015 HFI 0.029 HI, Mann-Whitney test).Different sex profiles influence people, current or past capacity to menstruate, migraine. Measurement was feasible warrants further investigation.

Language: Английский

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Biomarkers of Migraine: An Integrated Evaluation of Preclinical and Clinical Findings

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5334 - 5334

Published: March 10, 2023

In recent years, numerous efforts have been made to identify reliable biomarkers useful in migraine diagnosis and progression or associated with the response a specific treatment. The purpose of this review is summarize alleged diagnostic therapeutic found biofluids discuss their role pathogenesis disease. We included most informative data from clinical preclinical studies, particular emphasis on calcitonin gene-related peptide (CGRP), cytokines, endocannabinoids, other biomolecules, majority which are related inflammatory aspects mechanisms migraine, as well actors that play potential issues affecting biomarker analysis also discussed, such how deal bias confounding data. CGRP biological factors trigeminovascular system may offer intriguing novel precision medicine opportunities, although stability samples used, effects age, gender, diet, metabolic should be considered.

Language: Английский

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The association between lipid-related obesity indicators and severe headache or migraine: a nationwide cross sectional study from NHANES 1999 to 2004

Lipids in Health and Disease, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 11, 2025

Abstract Background The connection between lipid-related obesity indices and severe headache or migraine in young middle-aged people aged 20–60 remains ambiguous, there are gaps the discriminative ability of different indicators for headaches migraines. Consequently, we set out to look into this association utilizing National Health Nutrition Examination Survey (NHANES) data from 1999 2004. Methods After values waist-to-height ratio (WHtR), body-mass index (BMI), body roundness (BRI), visceral adiposity (VAI), lipid accumulation product (LAP), triglyceride glucose (TyG), cardiac metabolism (CMI), waist Index (WTI), conicity (CI) weight-adjusted (WWI) were estimated, with minimal sufficient adjustment confounders determined by directed acyclic graph (DAG), weighted univariable multivariable logistic regression analyses carried ascertain relationship them migraine. Stratified analysis cross-effect implemented examine variability intergroup correlations. Restricted cubic splines (RCS) receiver operating characteristic (ROC) then employed nonliner relationships its discriminatory migraine, respectively. Results 3354 United States adults involved our study, whom 839 (25.01%) had adjusting relevant covariables, WHtR, BRI, BMI, LAP, WTI VAI all associated WHtR (OR = 6.38, 95% CI: 2.25,18.09, P < 0.01) showed best predictive ability. Additionally, BRI demonstrated linear dose-response prevalence (all overall 0.05, non−linearity > 0.05). Conclusions Among those ten evaluated BMI positive individuals within Our study can provide important insight epidemiological research comprehensive management obese patients

Language: Английский

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Prolactin and oxytocin: potential targets for migraine treatment

The Journal of Headache and Pain, Journal Year: 2023, Volume and Issue: 24(1)

Published: March 26, 2023

Abstract Migraine is a severe neurovascular disorder of which the pathophysiology not yet fully understood. Besides role inflammatory mediators that interact with trigeminovascular system, cyclic fluctuations in sex steroid hormones are involved dimorphism migraine attacks. In addition, pituitary-derived hormone prolactin and hypothalamic neuropeptide oxytocin have been reported to play modulating contribute its sex-dependent differences. The current narrative review explores relationship between these two migraine. We describe physiological oxytocin, pain, potential therapies targeting or their receptors. summary, nociception opposite ways. Both operate at peripheral central levels, however, has pronociceptive effect, while appears an antinociceptive effect. Therefore, treatment should aim block effects using receptor antagonists monoclonal antibodies specifically acting migraine-pain related structures. This action be local order avoid decrease levels throughout body associated adverse effects. contrast, enhance signalling effects, for example intranasal administration possibly other agonists. Interestingly, co-localized estrogen receptors as well calcitonin gene-related peptide receptor, providing positive perspective on possibilities adequate pharmacological nociceptive pathways. Nevertheless, many questions remain answered. More particularly, there insufficient data men correct dosing according differences, hormonal changes comorbidities. above remains major challenge future development.

Language: Английский

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The Registry for Migraine (REFORM) study: methodology, demographics, and baseline clinical characteristics

The Journal of Headache and Pain, Journal Year: 2023, Volume and Issue: 24(1)

Published: June 11, 2023

Erenumab has demonstrated effectiveness for prevention of migraine attacks, but the treatment is costly, and a considerable proportion patients do not respond to it. The Registry Migraine study (REFORM) was initiated discover biomarkers that can predict response erenumab in with migraine. specific objective investigate differences efficacy based on clinical information, blood-based biomarkers, structural functional magnetic resonance imaging (MRI), intravenous infusion calcitonin gene-related peptide (CGRP). In this first report REFORM study, we provide comprehensive description methodology, present baseline characteristics population.The single-center, prospective, longitudinal cohort adults who were scheduled receive preventive as part separate, open-label, single-arm phase IV trial. included four periods: 2-week screening period (Weeks -6 -5), 4-week (Week -4 Day 1), 24-week (Day 1 Week 24), follow-up without 25 48). Demographic recorded using semi-structured interview, whilst outcome data obtained headache diary, patient-reported outcomes, blood sampling, brain MRI, responsiveness CGRP.The enrolled 751 participants, mean age ± SD 43.8 12.2 years, which 88.8% (n = 667) female. At enrollment, 64.7% 486) diagnosed chronic migraine, 30.2% 227) had history aura. monthly days (MMDs) 14.5 7.0. Concomitant medications used by 48.5% 364) 39.9% 300) failed ≥ 4 medications.The population high burden frequent use concomitant medications. representative specialized clinics. Future publications will results investigations presented article.The sub-studies registered ClinicalTrials.gov (NCT04592952; NCT04603976; NCT04674020).

Language: Английский

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Sex differences in migraine attack characteristics: A longitudinal E‐diary study

Headache The Journal of Head and Face Pain, Journal Year: 2023, Volume and Issue: 63(3), P. 333 - 341

Published: March 1, 2023

Abstract Objective In this prospective cohort study, characteristics of perimenstrual and non‐perimenstrual migraine attacks in women were compared with men. Background Women report longer more accompanying symptoms than men cross‐sectional questionnaire studies, but has not been confirmed longitudinal studies. Supposed differences could result from different specific to attacks, or general. Methods This study was performed among patients who treated at the Leiden Headache Clinic. We assessed attack between prospectively followed by a previously validated electronic headache diary. The primary outcome “attack” duration. Differences (Days −2 +3 menstrual cycle) versus corrected for age, chronic migraine, medication overuse headache. Results A total 1347 284 included, reflecting preponderance prevalence. Crude median (first third quartile [Q1−Q3]) duration 32.1 [17.7–53.6] h, 36.7 [21.9–62.4] h 44.4 [17.9–79.0] women. After correction confounding, 1.62 (95% confidence interval [CI] 1.47–1.79; p < 0.001) 1.15 CI 1.05–1.25; = 0.003) times mean relapse percentage 9.2%, 12.6% 15.7% attacks. Relapse risk greater (odds ratio [OR] 2.39, 95% 1.93–2.95; 0.001), (OR 1.18, 0.97–1.45; 0.060) Migraine often accompanied photophobia, phonophobia, nausea, less aura. Conclusion Compared men, both are associated symptoms. sex‐specific approach treatment research is needed.

Language: Английский

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