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TWIK-related spinal cord potassium channel (TRESK) background potassium channels have a key role in controlling resting membrane potential and excitability of sensory neurons. A frameshift mutation leading to complete loss of TRESK function has been identified in members of a family suffering from migraine with aura. In the present study, we examined the role of TRESK channels on nociceptor function in mice.
Learn More >To estimate the prevalence, burden and current treatment of disabling primary headaches in a large sample of the Greek population aged 18-70 years old.
Learn More >Botulinum neurotoxin (BoNT) is an effective treatment for many neurologic disorders. This article gives a comprehensive overview of the clinical applications of BoNT across the field of neurology.
Learn More >Migraine affects ∼15% of the world's population greatly diminishing their quality of life. Current preventative treatments are effective in only a subset of migraine patients, and while cannabinoids appear beneficial in alleviating migraine symptoms, central nervous system (CNS) side effects limit their widespread use. We developed peripherally-restricted cannabinoids (PRCBs) that relieve chronic pain symptoms of cancer and neuropathies, without appreciable CNS side effects or tolerance development. Here we determined PRCB effectiveness in alleviating hypersensitivity symptoms in mouse models of migraine and medication overuse headache (MOH). Chronic glyceryl trinitrate (GTN, 10 mg/kg) administration led to increased sensitivity to mechanical stimuli, and increased expression of phosphorylated protein kinase A (p-PKA), neuronal nitric oxide synthase (nNOS), and transient receptor potential ankyrin 1 (TRPA1) proteins in trigeminal ganglia. PRCB pretreatment, but not posttreatment, prevented behavioral and biochemical correlates of GTN-induced sensitization. Low pH- and allyl isothiocyanate-activated currents in acutely isolated trigeminal neurons were reversibly attenuated by PRCB application. Chronic GTN treatment significantly enhanced these currents. Chronic sumatriptan treatment also led to development of allodynia to mechanical and cold stimuli which was slowly reversible after sumatriptan discontinuation. Subsequent challenge with a previously ineffective low-dose GTN (0.1-0.3 mg/kg) revealed latent behavioral sensitization and increased expression of p-PKA, nNOS, and TRPA1 proteins in trigeminal ganglia. PRCB pretreatment prevented all behavioral and biochemical correlates of allodynia and latent sensitization. Importantly, chronic PRCB treatment alone did not produce any behavioral or biochemical signs of sensitization. These data validate peripheral cannabinoid receptors as potential therapeutic targets in migraine and MOH.
Learn More >The International Headache Society criteria were written in order to help physicians establish a headache diagnosis. However, sometimes children with headache do not seem to fit any diagnosis. The purpose of our study was to assess the application of the criteria in a clinical setting.
Learn More >In this study we used nitroglycerin (NTG)-induced migraine attacks as a translational human disease model. Static and dynamic functional connectivity (FC) analyses were applied to study the associated functional brain changes. A spontaneous migraine-like attack was induced in five episodic migraine (EM) patients using a NTG challenge. Four task-free functional magnetic resonance imaging (fMRI) scans were acquired over the study: baseline, prodromal, full-blown, and recovery. Seed-based correlation analysis (SCA) was applied to fMRI data to assess static FC changes between the thalamus and the rest of the brain. Wavelet coherence analysis (WCA) was applied to test time-varying phase-coherence changes between the thalamus and salience networks (SNs). SCA results showed significantly FC changes between the right thalamus and areas involved in the pain circuits (insula, pons, cerebellum) during the prodromal phase, reaching its maximal alteration during the full-blown phase. WCA showed instead a loss of synchronisation between thalami and SN, mainly occurring during the prodrome and full-blown phases. These findings further support the idea that a temporal change in thalamic function occurs over the experimentally induced phases of NTG-induced headache in migraine patients. Correlation of FC changes with true clinical phases in spontaneous migraine would validate the utility of this model.
Learn More >Migraine is the second largest cause of years lost to disability globally among all diseases, with a worldwide prevalence over 1 billion. Despite the global burden of migraine, few classes of therapeutics have been specifically developed to combat migraine. After 30 years of translational research, calcitonin gene-related peptide (CGRP) inhibitors have emerged as a promising new tool in the prevention of migraine. Like all new therapeutics; however, we have limited real-world experience and CGRP has several known systemic actions that warrant consideration. This article provides a narrative review of the evidence for CGRP antagonists and summarises the known and potential side effects that should be considered.
Learn More >Primary headaches are one of the most common conditions; migraine being most prevalent. Recent work on the pathophysiology of migraine suggests a mismatch in the communication or tuning of the trigeminovascular system, leading to sensitization and the release of calcitonin gene-related peptide (CGRP). In the current Opinion, we use the up-to-date molecular understanding of mechanisms behind migraine pain, to provide novel aspects on how to modify the system and for the development of future treatments; acute as well as prophylactic. We explore the distribution and the expression of neuropeptides themselves, as well as certain ion channels, and most importantly how they may act in concert as modulators of excitability of both the trigeminal C neurons and the Aδ neurons.
Learn More >Tension-type headache (TTH) is the most prevalent primary headache disorder. We assessed the cross-sectional impact of TTH on health related quality of life (HRQoL) in a general population. We also examined the association of HRQoL scores with headache frequency, disability, medication overuse, poor self-rated health, psychiatric comorbidity, and pain sensitivity in individuals with TTH.
Learn More >To evaluate the measurement properties of all three domains of the Migraine-Specific Quality of Life questionnaire version 2.1 (MSQ v2.1) electronic patient-reported outcome (ePRO) to assess the functional impact of migraine in patients with episodic or chronic migraine (CM); and identify meaningful within-patient change thresholds for the Role Function-Restrictive (RFR), Role Function-Preventive (RFP), and Emotional Function (EF) domains.
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