The journal of headache and pain
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Spreading depolarization (SD) is a complex event that induces significant cellular stress in the central nervous system, leading to a robust inflammatory response without causing cell death in healthy tissues which may be called as neuro-parainflammation. Research has established a clear link between SD and the activation of pro-inflammatory pathways, particularly through the release of cytokines like interleukin-1β and tumor necrosis factor-α, and the involvement of inflammatory mediators such as cyclooxygenase-2 and high mobility group box 1 (HMGB1). Mechanistically, the opening of pannexin-1 (Panx1) channels and the activation of the (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome play critical roles in this process, facilitating the release of inflammatory signals that can exacerbate conditions like migraine. ⋯ Inflammation extends beyond the central nervous system to peripheral structures, including the meninges and trigeminovascular system, which are critical for headache initiation. Genetic factors, particularly familial hemiplegic migraine (FHM), exacerbate neuroinflammatory responses to SD, leading to increased susceptibility and prolonged headache behaviors. Collectively, these findings underscore the complex cellular interactions and innate inflammatory processes underlying SD and their relevance to migraine mechanisms, suggesting potential avenues for therapeutic intervention.
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Epidemiological studies on migraine are valuable for tracking disease trends, identifying risk factors, and informing treatment strategies. This study assessed the prevalence and annual incidence of clinically significant migraine in Israel from 2017 to 2022, with analyses stratified by age, sex, socioeconomic status, and district. Additionally, we compared relevant characteristics between adult migraine and non-migraine members of Leumit Healthcare Services (LHS), a national health provider in Israel. ⋯ This study provides a detailed epidemiological and clinical profile of patients with clinically significant migraine in LHS from 2017 to 2022. Notable trends include higher rates of migraine among patients with lower BMI, higher diastolic BP, lower glucose, and higher hemoglobin, suggesting potential modifiable risk factors.
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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.