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Meningeal mast cell-mediated mechanisms of cholinergic system modulation in neurogenic inflammation underlying the pathophysiology of migraine.

Growing evidence indicates that the parasympathetic system is implicated in migraine headache. However, the cholinergic mechanisms in the pathophysiology of migraine remain unclear. We investigated the effects and mechanisms of cholinergic modulation and a mast cell stabilizer cromolyn in the nitroglycerin-induced in-vivo migraine model and in-vitro hemiskull preparations in rats. Effects of cholinergic agents (acetylcholinesterase inhibitor neostigmine, or acetylcholine, and muscarinic antagonist atropine) and mast cell stabilizer cromolyn or their combinations were tested in the in-vivo and in-vitro experiments. The mechanical hyperalgesia was assessed by von-Frey hairs. Calcitonin gene-related peptide (CGRP) and C-fos levels were measured by enzyme-linked immunosorbent assay. Degranulation and count of meningeal mast cells were determined by toluidine-blue staining. Neostigmine augmented the nitroglycerin-induced mechanical hyperalgesia, trigeminal ganglion CGRP levels, brainstem CGRP and C-fos levels, as well as degranulation of mast cells in-vivo. Atropine inhibited neostigmine-induced additional increases in CGRP levels in trigeminal ganglion and brainstem while it failed to do this in the mechanical hyperalgesia, C-fos levels, and the mast cell degranulation. However, all systemic effects of neostigmine were abolished by cromolyn. The cholinergic agents or cromolyn did not alter basal release of CGRP, in-vitro, but cromolyn alleviated the CGRP-inducing effect of capsaicin while atropine failed to do it. These results ensure for a first time direct evidence that endogenous acetylcholine contributes to migraine pathology mainly by activating meningeal mast cells while muscarinic receptors are involved in CGRP release from trigeminal ganglion and brainstem, without excluding the possible role of nicotinic cholinergic receptors.

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Cerebral perfusion variance in new daily persistent headache and chronic migraine: an arterial spin-labeled MR imaging study.

New daily persistent headache (NDPH) and chronic migraine (CM) are two different types of headaches that might involve vascular dysregulation. There is still a lack of clarity about altered brain perfusion in NDPH and CM. This study aimed to investigate the cerebral perfusion variances of NDPH and CM using multi-delay pseudo-continuous arterial spin-labeled magnetic resonance imaging (pCASL-MRI).

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Current perspectives on the recognition and diagnosis of low CSF pressure headache syndromes.

Headaches occur when cerebrospinal fluid (CSF) pressure drops following dural puncture or trauma or spontaneously. As the features of these headaches and their accompanying symptoms might not be typical, low CSF pressure headache syndromes, and spontaneous intracranial hypotension in particular, are often misdiagnosed and underdiagnosed.

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Headache in pregnancy: a brief practical guide.

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Associations between Fatty Acid Intake and Tension-Type Headache: A Cross-Sectional Study.

Patients with tension-type headache (TTH) are characterized by recurrent pain that can become disabling. Identifying the dietary triggers of headaches has led to defining dietary strategies to prevent this disease. In fact, excessive dietary intake of Omega-6 (ω-6) fatty acids, or an ω-6: ω3 ≥ 5 ratio, typical of Western diets, has been associated with a higher prevalence of headaches. The objectives of the present study were to compare dietary fatty acid intake between participants with and without chronic TTH and to investigate the association between dietary fatty acid intake, pain characteristics, and quality of life in patients with chronic TTH.

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Expression of vasopressin and its receptors in migraine-related regions in CNS and the trigeminal system: influence of sex.

Hypothalamus is a key region in migraine attacks. In addition, women are disproportionately affected by migraine. The calcitonin gene-related peptide (CGRP) system is an important key player in migraine pathophysiology. CGRP signaling could be a target of hormones that influence migraine. Our aim is to identify the expression of vasopressin and its receptors in the brain and in the trigeminovascular system with focus on the migraine-related regions and, furthermore, to examine the role of sex on the expression of neurohormones in the trigeminal ganglion.

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Inter-individual variability in mechanical pain sensation in patients with cervicogenic headache: an explorative study.

Currently, evidence for effective physiotherapy interventions in patients with cervicogenic headache (CeH) is inconsistent. Although inter-individual variability in pain response is predictive for successful physiotherapy interventions, it was never explored in patients with CeH. Therefore the objective of the current study was to explore inter-individual variability in mechanical pain sensation, and its association with biopsychosocial-lifestyle (BPSL) characteristics in patients with CeH. A cross-sectional explorative analysis of inter-individual variability in mechanical pain sensation in 18 participants with CeH (29-51 years) was conducted. Inter-individual variability in mechanical pain sensation (standard deviations (SDs), F-statistics, Measurement System Analysis) was deducted from bilateral pressure pain thresholds of the suboccipitals, erector spine, tibialis anterior. BPSL-characteristics depression, anxiety, stress (Depression Anxiety Stress Scale-21), quality of life (Headache Impact Test-6), sleep-quality (Pittsburgh Sleep Quality Index), and sedentary time (hours/week) were questioned. Inter-individual variability in mechanical pain sensation explained 69.2% (suboccipital left), 86.8% (suboccipital right), 94.6% (erector spine left), 93.2% (erector spine right), 91.7% (tibialis anterior left), and 82% (tibialis anterior right) of the total variability in patients with CeH. The significant p-values and large F-statistic values indicate inter-individual differences in SDs. Significant associations between (1) lower quality of life and lower SDs of the suboccipital left PPT (p .005), and (2) longer sedentary time and higher SDs of the suboccipital left PPT (p .001) were observed. Results from our explorative study could suggest inter-individual variability in mechanical pain sensation at the left suboccipitals which associates with quality of life and sedentary time. These novel findings should be considered when phenotyping patients and 'individually' match interventions.

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Expanding the clinical spectrum of idiopathic intracranial hypertension.

Idiopathic intracranial hypertension (IIH) is a disorder of raised intracranial pressure (ICP). Although the majority of patients with IIH present classically with headache and papilledema, some patients may have unusual presentations or manifestations. Recent advancements in neuroimaging have facilitated the identification of other presentations associated with IIH. This review provides an overview of the expanding clinical spectrum of IIH.

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Diagnosing new daily persistent headache in children and adolescents: A survey of clinicians.

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Is prednisone still a reasonable option in the treatment of withdrawal headache in patients with chronic migraine and medication overuse headache in the age of CGRP antibodies? A narrative review.

Along with the development of novel migraine therapies as the monoclonal antibodies against calcitonin gene-related peptide (CGRP) and its receptor, the question arises if the treatment of chronic migraine (CM) and medication overuse headache (MOH) must be reconsidered. Have previous therapeutic approaches, including glucocorticoids, lost their role in the management of this debilitating disorder? In this narrative review, we present an overview of the available treatment options in CM and MOH in light of CGRP antibodies as well as an evaluation of the role of glucocorticoids in withdrawal therapy.

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