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PREMISE:Migraine is a complex neurologic disorder that leads to significant disability, yet remains poorly understood. PROBLEM:One potential triggering mechanism in migraine with aura is cortical spreading depression, which can activate the trigeminal nociceptive system both peripherally and centrally in animal models. A primary neuropeptide of the trigeminal system is calcitonin gene-related peptide, which is a potent vasodilatory peptide and is currently a major therapeutic target for migraine treatment. Despite the importance of both cortical spreading depression and calcitonin gene-related peptide in migraine, the relationship between these two players has been relatively unexplored. However, recent data suggest several potential vascular and neural connections between calcitonin gene-related peptide and cortical spreading depression. CONCLUSION:This review will outline calcitonin gene-related peptide-cortical spreading depression connections and propose a model in which cortical spreading depression and calcitonin gene-related peptide act at the intersection of the vasculature and cortical neurons, and thus contribute to migraine pathophysiology.

Objective: To identify and disseminate research priorities for the headache field that should be areas of research focus during the next 10 years. Background: Establishing research priorities helps focus and synergize the work of headache investigators, allowing them to reach the most important research goals more efficiently and completely. Methods: The Headache Research Priorities organizing and executive committees and working group chairs led a multistakeholder and international group of experts to develop headache research priorities. The research priorities were developed and reviewed by clinicians, scientists, people with headache, representatives from headache organizations, health‐care industry representatives, and the public. Priorities were revised and finalized after receiving feedback from members of the research priorities working groups and after a public comment period. Results: Twenty‐five research priorities across eight categories were identified: human models, animal models, pathophysiology, diagnosis and management, treatment, inequities and disparities, research workforce development, and quality of life. The priorities address research models and methods, development and optimization of outcome measures and endpoints, pain and non‐pain symptoms of primary and secondary headaches, investigations into mechanisms underlying headache attacks and chronification of headache disorders, treatment optimization, research workforce recruitment, development, expansion, and support, and inequities and disparities in the headache field. The priorities are focused enough that they help to guide headache research and broad enough that they are widely applicable to multiple headache types and various research methods. Conclusions: These research priorities serve as guidance for headache investigators when planning their research studies and as benchmarks by which the headache field can measure its progress over time. These priorities will need updating as research goals are met and new priorities arise. Plain Language Summary: The American Headache Society led a large, international, multistakeholder process to identify headache research topics that should be prioritized during the next 10 years. With input from headache clinicians, scientists, people with headache, representatives from headache organizations, health‐care industry representatives, and the public, 25 research priorities within 8 categories were identified. These research priorities can help guide headache researchers when planning their studies and as benchmarks by which the headache field can measure its progress over time. [ABSTRACT FROM AUTHOR]

Introduction Stem cell niches in adult organs play important roles in maintaining organ integrity in the setting of normal cellular turnover and injury. These microenvironments are unique and control intrinsic [...], In cystic fibrosis (CF), a lack of functional CF transmembrane conductance regulator (CFTR) chloride channels causes defective secretion by submucosal glands (SM[G.sub.s]), leading to persistent bacterial infection that damages airways and necessitates tissue repair. SM[G.sub.s] are also important niches for slow-cycling progenitor cells (SCP[C.sub.s]) in the proximal airways, which may be involved in disease-related airway repair. Here, we report that calcitonin generelated peptide (CGRP) activates CFTR-dependent SMG secretions and that this signaling pathway is hyperactivated in CF human, pig, ferret, and mouse SM[G.sub.s]. Since CGRP-expressing neuroendocrine cells reside in bronchiolar SCPC niches, we hypothesized that the glandular SCPC niche may be dysfunctional in CF. Consistent with this hypothesis, CFTR-deficient mice failed to maintain glandular SCP[C.sub.s] following airway injury. In wild-type mice, CGRP levels increased following airway injury and functioned as an injury-induced mitogen that stimulated SMG progenitor cell proliferation in vivo and altered the proliferative potential of airway progenitors in vitro. Components of the receptor for CGRP (RAMP1 and CLR) were expressed in a very small subset of SCP[C.sub.s], suggesting that CGRP indirectly stimulates SCPC proliferation in a non-cell-autonomous manner. These findings demonstrate that CGRP-dependent pathways for CFTR activation are abnormally upregulated in CF SM[G.sub.s] and that this sustained mitogenic signal alters properties of the SMG progenitor cell niche in CF airways. This discovery may have important implications for injury/repair mechanisms in the CF airway.

Migraine is a disabling neurological disease characterized by moderate or severe headaches and accompanied by sensory abnormalities, e.g., photophobia, allodynia, and vertigo. It affects approximately 15% of people worldwide. Despite advancements in current migraine therapeutics, mechanisms underlying migraine remain elusive. Within the central nervous system, studies have hinted that the cerebellum may play an important sensory integrative role in migraine. More specifically, the cerebellum has been proposed to modulate pain processing, and imaging studies have revealed cerebellar alterations in migraine patients. This review aims to summarize the clinical and preclinical studies that link the cerebellum to migraine. We will first discuss cerebellar roles in pain modulation, including cerebellar neuronal connections with pain-related brain regions. Next, we will review cerebellar symptoms and cerebellar imaging data in migraine patients. Lastly, we will highlight the possible roles of the neuropeptide calcitonin gene-related peptide (CGRP) in migraine symptoms, including preclinical cerebellar studies in animal models of migraine. [ABSTRACT FROM AUTHOR]