9a4c96a47be0d51e25293eb9d0ca3cf7 320000.pdf d1f599b7a5cfee1c9a12df74aa653bca2c5a072f 320000.pdf 09024e1caa3c24d2c7fd70926055a84923c05b4bad0a478c8e8a8adac8c27171 320000.pdf Title: The Role of Glial Cells in Different Phases of Migraine: Lessons from Preclinical Studies Subject: Migraine is a complex and debilitating neurological disease that affects 15% of the population worldwide. It is defined by the presence of recurrent severe attacks of disabling headache accompanied by other debilitating neurological symptoms. Important advancements have linked the trigeminovascular system and the neuropeptide calcitonin gene-related peptide to migraine pathophysiology, but the mechanisms underlying its pathogenesis and chronification remain unknown. Glial cells are essential for the correct development and functioning of the nervous system and, due to its implication in neurological diseases, have been hypothesised to have a role in migraine. Here we provide a narrative review of the role of glia in different phases of migraine through the analysis of preclinical studies. Current evidence shows that astrocytes and microglia are involved in the initiation and propagation of cortical spreading depolarization, the neurophysiological correlate of migraine aura. Furthermore, satellite glial cells within the trigeminal ganglia are implicated in the initiation and maintenance of orofacial pain, suggesting a role in the headache phase of migraine. Moreover, microglia in the trigeminocervical complex are involved in central sensitization, suggesting a role in chronic migraine. Taken altogether, glial cells have emerged as key players in migraine pathogenesis and chronification and future therapeutic strategies could be focused on targeting them to reduce the burden of migraine. Keywords: migraine; glia; astrocyte; microglia; satellite glial cell; cortical spreading depolarization; orofacial pain; headache; chronic migraine; migraine chronification Author: Marta Vila-Pueyo, Otilia Gliga, Víctor José Gallardo and Patricia Pozo-Rosich Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Aug 8 09:29:58 2023 CEST ModDate: Tue Aug 8 09:35:50 2023 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 16 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1518723 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- RVAGIN+VnURWPalladioL Type 1 Custom yes yes no 10 0 EYYOGN+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 DFQXMD+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 ORFPWQ+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 YSPQJI+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 46 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 49 0 HBBNGB+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 81 0 HBBNGD+PalatinoLinotype TrueType WinAnsi yes yes no 84 0 HBBNGF+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 87 0 HBBNGB+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 110 0 HBBNGD+PalatinoLinotype TrueType WinAnsi yes yes no 113 0 HBBNGF+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 116 0 QDCWHF+EURM10 Type 1 Builtin yes yes no 123 0 HBBNGB+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 139 0 HBBNGD+PalatinoLinotype TrueType WinAnsi yes yes no 142 0 HBBNGF+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 145 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2026-01-20 03:08:45 CET RepresentationInformation: 320000.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2026-01-19 14:16:19 CET Size: 1518723 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 493 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Children: Item: Title: Migraine Destination: subsection.1.1 Item: Title: Glial Cells Destination: subsection.1.2 Item: Title: Overview of the Role of Glia in Neurological Diseases Destination: subsection.1.3 Item: Title: Role of Glia in Cortical Spreading Depolarization: Implications for the Migraine Aura Phase Destination: section.2 Item: Title: Role of Glia in Orofacial Pain: Implications for the Migraine Headache Phase Destination: section.3 Item: Title: Role of Glia in Chronic Pain: Implications for Migraine Chronification Destination: section.4 Item: Title: Targeting Glia: Potential Future Therapeutic and Diagnostic Opportunities for Migraine Destination: section.5 Item: Title: Conclusions and Future Perspectives Destination: section.6 Item: Title: References Destination: section.7 Info: Title: The Role of Glial Cells in Different Phases of Migraine: Lessons from Preclinical Studies Author: Marta Vila-Pueyo, Otilia Gliga, Víctor José Gallardo and Patricia Pozo-Rosich Subject: Migraine is a complex and debilitating neurological disease that affects 15% of the population worldwide. It is defined by the presence of recurrent severe attacks of disabling headache accompanied by other debilitating neurological symptoms. Important advancements have linked the trigeminovascular system and the neuropeptide calcitonin gene-related peptide to migraine pathophysiology, but the mechanisms underlying its pathogenesis and chronification remain unknown. Glial cells are essential for the correct development and functioning of the nervous system and, due to its implication in neurological diseases, have been hypothesised to have a role in migraine. Here we provide a narrative review of the role of glia in different phases of migraine through the analysis of preclinical studies. Current evidence shows that astrocytes and microglia are involved in the initiation and propagation of cortical spreading depolarization, the neurophysiological correlate of migraine aura. Furthermore, satellite glial cells within the trigeminal ganglia are implicated in the initiation and maintenance of orofacial pain, suggesting a role in the headache phase of migraine. Moreover, microglia in the trigeminocervical complex are involved in central sensitization, suggesting a role in chronic migraine. Taken altogether, glial cells have emerged as key players in migraine pathogenesis and chronification and future therapeutic strategies could be focused on targeting them to reduce the burden of migraine. 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