natriuretic-peptide--brain and Migraine-with-Aura

Migraine with aura (MA) was found to be associated with increased cardiovascular events (CVE), whereas left ventricular (LV) mechanics were not previously studied in migraineurs. In this study, we aimed to assess LV functions with the utility of two-dimensional speckle tracking echocardiography (2D-STE) and cardiac biomarkers with respect to the headache-free and attack periods and frequency of migraine attacks. Sixty-eight patients with MA were enrolled. During headache-free and attack periods, all patients underwent echocardiographic examination including 2D-STE, and cardiac biomarkers, B-type natriuretic peptide (BNP) and high sensitive cTnT (hs-cTnT) were studied. The impact of headache periods and frequency of attacks on cardiac mechanics and biomarkers were investigated. The mean age of study population was 38.1 ± 7.7 years (56 female) and thirty-one patients (44.6%) had high-frequency migraine attacks. Patients who suffered headache-attack periods had higher frequency of detectable hs-cTnT levels and increased NT-proBNP values which did not differ between low- and high-frequency migraine groups in both periods. Headache attack periods had decreased global longitudinal strain (GLS), increased LV end-systolic volume (LVESV), E/Em ratio and LV torsion (LV-tor) during headache-attack periods. In multivariate analysis; LVESV, LV-tor and high frequency of migraine attacks were associated with decreased GLS (≤ - 20.8), (p 0.038, p 0.026 and p 0.013, respectively). Consequently, 2D-STE findings revealed that migraine attacks, especially with increasing frequencies, could have negative impact on LV mechanics, which adds a new perspective about increased CVE in subjects with MA.

Topics: Adult; Biomarkers; Echocardiography, Doppler, Pulsed; Female; Humans; Male; Middle Aged; Migraine with Aura; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; Risk Factors; Stroke Volume; Troponin T; Ventricular Dysfunction, Left; Ventricular Function, Left

On trigeminal ganglion neurons, pain-sensing P2X3 receptors are constitutively inhibited by brain natriuretic peptide via its natriuretic peptide receptor-A. This inhibition is associated with increased P2X3 serine phosphorylation and receptor redistribution to non-lipid raft membrane compartments. The natriuretic peptide receptor-A antagonist anantin reverses these effects. We studied whether P2X3 inhibition is dysfunctional in a genetic familial hemiplegic migraine type-1 model produced by introduction of the human pathogenic R192Q missense mutation into the mouse CACNA1A gene (knock-in phenotype). This model faithfully replicates several properties of familial hemiplegic migraine type-1, with gain-of-function of CaV2.1 Ca(2+) channels, raised levels of the algogenic peptide calcitonin gene-related peptide, and enhanced activity of P2X3 receptors in trigeminal ganglia.. In knock-in neurons, anantin did not affect P2X3 receptor activity, membrane distribution, or serine phosphorylation level, implying ineffective inhibition by the constitutive brain natriuretic peptide/natriuretic peptide receptor-A pathway. However, expression and functional properties of this pathway remained intact together with its ability to downregulate TRPV1 channels. Reversing the familial hemiplegic migraine type-1 phenotype with the CaV2.1-specific antagonist, ω-agatoxin IVA restored P2X3 activity to wild-type level and enabled the potentiating effects of anantin again. After blocking calcitonin gene-related peptide receptors, P2X3 receptors exhibited wild-type properties and were again potentiated by anantin.. P2X3 receptors on mouse trigeminal ganglion neurons are subjected to contrasting modulation by inhibitory brain natriuretic peptide and facilitatory calcitonin gene-related peptide that both operate via complex intracellular signaling. In the familial hemiplegic migraine type-1 migraine model, the action of calcitonin gene-related peptide appears to prevail over brain natriuretic peptide, thus suggesting that peripheral inhibition of P2X3 receptors becomes insufficient and contributes to trigeminal pain sensitization.

Topics: Animals; Calcitonin Gene-Related Peptide Receptor Antagonists; Disease Models, Animal; Gene Knock-In Techniques; Mice; Migraine with Aura; Models, Biological; Natriuretic Peptide, Brain; omega-Agatoxin IVA; Peptides, Cyclic; Phenotype; Purinergic P2X Receptor Antagonists; Receptors, Atrial Natriuretic Factor; Receptors, Calcitonin Gene-Related Peptide; Receptors, Purinergic P2X3; Sensory Receptor Cells; Trigeminal Ganglion; TRPV Cation Channels