The journal of headache and pain
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Substance P, previously dismissed as a therapeutic target for migraine due to the failure of neurokinin-1 receptor antagonists, warrants renewed attention. Building on the success of therapies targeting the calcitonin gene-related peptide (CGRP) system and pituitary adenylate cyclase-activating peptide (PACAP) in migraine prevention, which highlight the importance of targeting peptides, this proposal reexamines substance P as a mediator in migraine pathophysiology. Using an established methodological framework, migraine-inducing properties of substance P can be evaluated through randomized, double-blind, placebo-controlled crossover studies involving healthy volunteers and individuals with a history of migraine. This approach aims to establish proof of concept for substance P's role in migraine, laying the groundwork for investigations with animal and cell-based models and advancing the development of innovative treatments for patients refractory to current therapies.
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Letter Review
Fitness-to-work considerations in the paradigmatic pain condition of headache disorder.
Headache disorders are common, including in the working population. Clinicians caring for patients with headache need to be aware of work-related factors as potential causes or triggers of headache disorders, and consider the impact of headache on fitness-to-work, especially in safety-sensitive and decision-critical roles. Such fitness-to-work determination should include individualized consideration of the nature of the headache disorder itself, the pattern of the headache, the impact of sleep deprivation on the headache as it relates to fitness to do shiftwork, medication and substance side effects, fitness-to-work implications of associated medical or psychiatric conditions, and the potential of symptom feigning or malingering for secondary gain. As clinicians often struggle with fitness-to-work determinations, a structured approach to fitness-to-work assessments in headache conditions and other pain conditions would improve clarity for clinicians and increase the quality of care provided to patients, with potential benefits for workplace safety and policy in this arena as well.
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Proton pump inhibitor (PPI) drugs are widely used and are among the most significant achievements of modern pharmacology. Their primary purpose is treating and preventing gastric acid-related disorders. Migraine and PPI intake are prevalent, and many people are affected by both. In the last few years, a potential link between PPI intake and the development of headaches-especially migraine-has come to increased attention. In this review, we critically examine the scientific data concerning the co-occurrence of these two entities. ⋯ A relation between the prevalence of migraine and the use of PPIs on a population and personal level seems likely. Although PPIs have many advantages, they should be prescribed with caution, especially in patients who suffer from headaches and migraine. In this narrative review, we aim to critically evaluate existing data and offer a potential approach to accurately identify any connections and interactions, leading to a better understanding of how these conditions may influence each other.
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A key unanswered question in migraine neurobiology concerns the mechanisms that make the brain of migraineurs susceptible to cortical spreading depression (CSD, a spreading depolarization that underlies migraine aura and may trigger the migraine pain mechanisms). Important insights into this question can be obtained by studying the mechanisms of facilitation of CSD initiation in genetic mouse models of the disease. These models, all generated from families with hereditary migraine, allow the investigation of the functional consequences of disease-causing mutations at the molecular, cellular, synaptic and neural circuit levels. In this review, after describing the available genetic mouse models of migraine, which all share increased susceptibility to experimentally induced CSD, we will discuss the functional alterations in their cerebral cortex and the mechanisms underlying the facilitation of CSD initiation in their cortex, as well as the insights that these mechanisms may give into the mechanisms of initiation of spontaneous CSDs in migraine.
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The term "aura" refers to a well-defined pattern of usually positive, progressive, and reversible neurological symptoms, with spreading depolarization as the underlying mechanism. While commonly associated with migraine, aura can also occur in other neurological disorders (i.e., cerebrovascular disorders). However, current terminology inadequately describes its different underlying clinical etiologies. ⋯ This nuanced classification aims to aid in the diagnostic evaluation and phenotyping of aura phenomenon, ultimately improving the diagnosis and management of the different associated neurological conditions. Moreover, it could promote effective communication and translational mechanistic research.