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Currently, there is no biologically based rationale for drug selection in migraine prophylactic treatment.
Learn More >ObjectiveTo determine whether the intravenous infusion of adrenomedullin, a potent vasodilator belonging to calcitonin family of peptides, provokes attacks of migraine in patients.MethodsTwenty migraine without aura patients participated in a placebo-controlled and double-blinded clinical study. In a randomized and crossover design the patients received an intravenous infusion of human adrenomedullin (19.9 picomole/kg/min) or placebo (saline) administrated via an automated intravenous pump (20 minutes). The patients participated in two study days with washout period of minimum of seven days. The primary outcome of the study was predefined as a difference in migraine incidence (0-12 h) and the secondary outcome were the headache intensity score's area under curve (AUC) and the (AUC ) for MAP, flushing and HR.ResultsEleven migraine without aura patients (55%) fulfilled migraine attacks criteria after adrenomedullin infusion in comparison to only three patients reported attack (15%) after placebo ( 0.039). We found that patients reported in a period of (0-12 hours) stronger headache intensity after adrenomedullin in comparison to placebo infusion ( 0.035). AUC for HR and, flushing ( < 0.05) were significant and MAP ( = 0.502) remain unchanged. Common adverse events reported were facial flushing, heat sensation and palpitation ( <0.001)ConclusionOur data implicate adrenomedullin in migraine pathogenesis. This suggests that adrenomedullin and/or its receptors are novel therapeutic targets for the treatment of migraine. However, we cannot discount for the possibility that adrenomedullin may be acting through the canonical CGRP receptor.
Learn More >The neuromodulator calcitonin gene-related peptide (CGRP) is known to facilitate nociceptive transmission in the superficial laminae of the spinal trigeminal nucleus caudalis (Sp5C). The central effects of CGRP in the Sp5C are very likely to contribute to the activation of central nociceptive pathways leading to attacks of severe headaches like migraine. To examine the potential impacts of CGRP on laminae I/II neurons at cellular and synaptic levels, we performed whole-cell patch-clamp recordings in juvenile mouse brainstem slices. First, we tested the effect of CGRP on cell excitability, focusing on neurons with tonically firing action potentials upon depolarizing current injection. CGRP (100 nM) enhanced tonic discharges together with membrane depolarization, an excitatory effect that was significantly reduced when the fast synaptic transmissions were pharmacologically blocked. However, CGRP at 500 nM was capable of exciting the functionally isolated cells, in a nifedipine-sensitive manner, indicating its direct effect on membrane intrinsic properties. In voltage-clamped cells, 100 nM CGRP effectively increased the frequency of excitatory synaptic inputs, suggesting its preferential presynaptic effect. Both CGRP-induced changes in cell excitability and synaptic drives were prevented by the CGRP receptor inhibitor BIBN 4096BS. Our data provide evidence that CGRP increases neuronal activity in Sp5C superficial laminae by dose-dependently promoting excitatory synaptic drive and directly enhancing cell intrinsic properties. We propose that the combination of such pre- and postsynaptic actions of CGRP might underlie its facilitation in nociceptive transmission in situations like migraine with elevated CGRP levels.
Learn More >Given the potential for obesity to complicate migraine treatment outcomes, there is a need to understand patterns and correlates of acute medication use among individuals with this comorbidity. Experience sampling methodology (ESM) was used to characterize patterns of acute medication use among those with migraine and overweight/obesity and to examine individual and momentary factors related to medication use (both migraine-specific and nonspecific medications). Women with migraine and overweight/obesity (N = 170) seeking behavioral migraine treatment completed questionnaires followed by 28 days of daily ESM headache diaries. Participants used medications to treat 71.9% of attacks, 20% of which were treated with migraine-specific medications. Participants were more likely to use medication in the context of longer and more severe attacks that started earlier in the day. Presence of aura and greater work-related pain interference uniquely related to migraine-specific medication use. Questionnaire-assessed factors were not related to medication use, although older age and higher educational attainment related to more frequent use. A substantial proportion of attacks were left untreated, suggesting unmet treatment needs in this population. Results also suggest that ESM-assessed factors are more salient correlates of medication use compared to questionnaires. Additional investigation of barriers to medication use is needed.
Learn More >To evaluate the impact of two calcitonin gene-related peptide (CGRP)-targeted monoclonal antibodies (mAbs), erenumab and galcanezumab, on the pharmacokinetic (PK) profile, safety, and tolerability of ubrogepant.
Learn More >Migraine has been associated with many comorbidities. However, lifestyle factors and the presence of comorbid diseases have not previously been extensively studied in the same sample. This study aimed to compare the prevalence of unhealthy lifestyle factors and comorbid diseases between patients with migraine and migraine-free controls with subgroup analyses to determine the pathophysiology and possible consequences.
Learn More >Migraine sufferers often exhibit photophobia and physical hypoactivity in the postdrome and interictal periods, for which no effective therapy currently exists. Cortical spreading depolarization (CSD) is a neural phenomenon underlying migraine aura. We previously reported that CSD induced trigeminal sensitization, photophobia, and hypomobility at 24 h in mice. Here, we examined the effects of CSD induction on light sensitivity and physical activity in mice at 48 h and 72 h. Trigeminal sensitization was absent at both time points. CSD-subjected mice exhibited significantly less ambulatory time in both light (P = 0.0074, the Bonferroni test) and dark (P = 0.0354, the Bonferroni test) zones than sham-operated mice at 72 h. CSD-subjected mice also exhibited a significantly shorter ambulatory distance in the light zone at 72 h than sham-operated mice (P = 0.0151, the Bonferroni test). Neurotropin® is used for the management of chronic pain disorders, mainly in Asian countries. The CSD-induced reductions in ambulatory time and distance in the light zone at 72 h were reversed by Neurotropin® at 0.27 NU/kg. Our experimental model seems to recapitulate migraine-associated clinical features observed in the postdrome and interictal periods. Moreover, Neurotropin® may be effective in ameliorating postdromal/interictal hypoactivity, especially in a light environment.
Learn More >Migraine is a complex, multifaceted, and disabling headache disease that is often complicated by gastrointestinal (GI) conditions, such as gastroparesis, functional dyspepsia, and cyclic vomiting syndrome (CVS). Functional dyspepsia and CVS are part of a spectrum of disorders newly classified as disorders of gut-brain interaction (DGBI). Gastroparesis and functional dyspepsia are both associated with delayed gastric emptying, while nausea and vomiting are prominent in CVS, which are also symptoms that commonly occur with migraine attacks. Furthermore, these gastric disorders are comorbidities frequently reported by patients with migraine. While very few studies assessing GI disorders in patients with migraine have been performed, they do demonstrate a physiological link between these conditions.
Learn More >To assess support for a causal relationship between hemostatic measures and migraine susceptibility using genetic instrumental analysis.
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