{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:25:47Z","timestamp":1790861147093,"version":"4.1.0"},"reference-count":62,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T00:00:00Z","timestamp":1751068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82274664"],"award-info":[{"award-number":["82274664"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82430124"],"award-info":[{"award-number":["82430124"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82004486"],"award-info":[{"award-number":["82004486"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Chronic migraine (CM) is a debilitating neurological disorder, yet the glial-specific mechanisms underlying its pathophysiology in the trigeminal nucleus caudalis (TNC)\u2014a critical hub for craniofacial pain processing\u2014remain poorly understood. Here, we employed single-nucleus RNA sequencing (snRNA-seq) to resolve cell-type-specific transcriptional landscapes in a nitroglycerin (NTG)-induced CM rat model, with a particular focus on microglia and astrocytes. We identified 19 transcriptional clusters representing nine major cell types, among which reactive microglia (NTG-Mic) and astrocytes (NTG-Asts) were markedly expanded. The NTG-Mic displayed a glycolysis-dominant, complement-enriched state, whereas the NTG-Asts exhibited concurrent activation of amino acid transport and cytokine signaling pathways. Pseudotime trajectory analysis revealed bifurcated glial activation paths, with NTG driving both cell types toward terminal reactive states. Intercellular communication inference uncovered suppressed homeostatic interactions (e.g., CSF1-CSF1R) alongside enhanced proinflammatory signaling (e.g., FGF1-FGFR2, PTN-SDC4), particularly affecting neuron\u2013glia and glia\u2013glia crosstalk. Together, these findings define a high-resolution atlas of glial reprogramming in CM, implicating state-specific metabolic\u2013immune transitions and dysregulated glial communication as potential targets for therapeutic intervention.<\/jats:p>","DOI":"10.3390\/biom15070942","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T07:55:43Z","timestamp":1751442943000},"page":"942","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Single-Nucleus Transcriptomics Reveals Glial Metabolic\u2013Immune Rewiring and Intercellular Signaling Disruption in Chronic Migraine"],"prefix":"10.3390","volume":"15","author":[{"given":"Shuangyuan","family":"Hu","sequence":"first","affiliation":[{"name":"School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zili","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqi","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyan","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longyao","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yuan","sequence":"additional","affiliation":[{"name":"School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingsheng","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"},{"name":"Key Laboratory of Acupuncture for Senile Disease, Chengdu University of Traditional Chinese Medicine, Ministry of Education, Chengdu 611137, China"},{"name":"Acupuncture & Chronobiology Key Laboratory of Sichuan Province, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/nrneurol.2016.93","article-title":"Chronic migraine: Risk factors, mechanisms and treatment","volume":"12","author":"May","year":"2016","journal-title":"Nat. Rev. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1016\/S0140-6736(20)32160-7","article-title":"Migraine: Epidemiology and systems of care","volume":"397","author":"Ashina","year":"2021","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/s11916-024-01228-4","article-title":"Influences of Genetic and Environmental Factors on Chronic Migraine: A Narrative Review","volume":"28","author":"Yeh","year":"2024","journal-title":"Curr. Pain Headache Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s10194-024-01800-8","article-title":"Altered immunity in migraine: A comprehensive scoping review","volume":"25","author":"Ha","year":"2024","journal-title":"J. Headache Pain"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/S1474-4422(19)30185-1","article-title":"Migraine and the trigeminovascular system-40 years and counting","volume":"18","author":"Ashina","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.it.2020.07.009","article-title":"Microglia and Astrocyte Crosstalk in Immunity","volume":"41","author":"Sacristan","year":"2020","journal-title":"Trends Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.neuron.2020.08.012","article-title":"Astrocyte Crosstalk in CNS Inflammation","volume":"108","author":"Linnerbauer","year":"2020","journal-title":"Neuron"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e101997","DOI":"10.15252\/embj.2019101997","article-title":"Microglial subtypes: Diversity within the microglial community","volume":"38","author":"Stratoulias","year":"2019","journal-title":"EMBO J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s10194-023-01707-w","article-title":"Microglia TREM1-mediated neuroinflammation contributes to central sensitization via the NF-kappaB pathway in a chronic migraine model","volume":"25","author":"Sun","year":"2024","journal-title":"J. Headache Pain"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2386","DOI":"10.1097\/j.pain.0000000000002229","article-title":"Astrocytes mediate migraine-related intracranial meningeal mechanical hypersensitivity","volume":"162","author":"Zhao","year":"2021","journal-title":"Pain"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1186\/s40001-024-01919-z","article-title":"A comprehensive exploration of astrocytes in migraine: A bibliometric and visual analysis","volume":"29","author":"Wei","year":"2024","journal-title":"Eur. J. Med. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1038\/s41586-024-07606-7","article-title":"Single-cell multiregion dissection of Alzheimer\u2019s disease","volume":"632","author":"Mathys","year":"2024","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1177\/0333102418762476","article-title":"Localization of migraine susceptibility genes in human brain by single-cell RNA sequencing","volume":"38","author":"Renthal","year":"2018","journal-title":"Cephalalgia"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1177\/0333102419877834","article-title":"Migraine-associated gene expression in cell types of the central and peripheral nervous system","volume":"40","author":"Vgontzas","year":"2019","journal-title":"Cephalalgia"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.trsl.2022.07.004","article-title":"Single-cell RNA sequencing in the context of neuropathic pain: Progress, challenges, and prospects","volume":"251","author":"Chen","year":"2023","journal-title":"Transl. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1806","DOI":"10.1016\/j.neuron.2022.03.003","article-title":"Human and mouse trigeminal ganglia cell atlas implicates multiple cell types in migraine","volume":"110","author":"Yang","year":"2022","journal-title":"Neuron"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Sureda-Gibert, P., Romero-Reyes, M., and Akerman, S. (2022). Nitroglycerin as a model of migraine: Clinical and preclinical review. Neurobiol. Pain, 12.","DOI":"10.1016\/j.ynpai.2022.100105"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.pneurobio.2019.02.002","article-title":"Nitroglycerin as a comparative experimental model of migraine pain: From animal to human and back","volume":"177","author":"Demartini","year":"2019","journal-title":"Prog. Neurobiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s10194-020-01145-y","article-title":"Calcitonin gene-related peptide facilitates sensitization of the vestibular nucleus in a rat model of chronic migraine","volume":"21","author":"Zhang","year":"2020","journal-title":"J. Headache Pain"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.cels.2019.03.003","article-title":"DoubletFinder: Doublet Detection in Single-Cell RNA Sequencing Data Using Artificial Nearest Neighbors","volume":"8","author":"McGinnis","year":"2019","journal-title":"Cell Syst."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Yang, S., Corbett, S.E., Koga, Y., Wang, Z., Johnson, W.E., Yajima, M., and Campbell, J.D. (2020). Decontamination of ambient RNA in single-cell RNA-seq with DecontX. Genome Biol., 21.","DOI":"10.1186\/s13059-020-1950-6"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","article-title":"Integrated analysis of multimodal single-cell data","volume":"184","author":"Hao","year":"2021","journal-title":"Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"D870","DOI":"10.1093\/nar\/gkac947","article-title":"CellMarker 2.0: An updated database of manually curated cell markers in human\/mouse and web tools based on scRNA-seq data","volume":"51","author":"Hu","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Valihrach, L., Matusova, Z., Zucha, D., Klassen, R., Benesova, S., Abaffy, P., Kubista, M., and Anderova, M. (2022). Recent advances in deciphering oligodendrocyte heterogeneity with single-cell transcriptomics. Front. Cell. Neurosci., 16.","DOI":"10.3389\/fncel.2022.1025012"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1126\/science.aaf6463","article-title":"Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system","volume":"352","author":"Marques","year":"2016","journal-title":"Science"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/j.cell.2021.01.010","article-title":"A pan-cancer single-cell transcriptional atlas of tumor infiltrating myeloid cells","volume":"184","author":"Cheng","year":"2021","journal-title":"Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/nbt.2859","article-title":"The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells","volume":"32","author":"Trapnell","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1038\/s41467-021-21246-9","article-title":"Inference and analysis of cell-cell communication using CellChat","volume":"12","author":"Jin","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"eaat7554","DOI":"10.1126\/science.aat7554","article-title":"Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation","volume":"363","author":"Sankowski","year":"2019","journal-title":"Science"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1016\/j.neuron.2021.01.027","article-title":"White matter aging drives microglial diversity","volume":"109","author":"Safaiyan","year":"2021","journal-title":"Neuron"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/s41392-023-01588-0","article-title":"Microglia in neurodegenerative diseases: Mechanism and potential therapeutic targets","volume":"8","author":"Gao","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"107843","DOI":"10.1016\/j.celrep.2020.107843","article-title":"Alzheimer\u2019s Patient Microglia Exhibit Enhanced Aging and Unique Transcriptional Activation","volume":"31","author":"Srinivasan","year":"2020","journal-title":"Cell Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e25552","DOI":"10.1002\/cne.25552","article-title":"Astrocyte ensheathment of calyx-forming axons of the auditory brainstem precedes accelerated expression of myelin genes and myelination by oligodendrocytes","volume":"532","author":"Heller","year":"2024","journal-title":"J. Comp. Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Alghamdi, B., and Fern, R. (2015). Phenotype overlap in glial cell populations: Astroglia, oligodendroglia and NG-2(+) cells. Front. Neuroanat., 9.","DOI":"10.3389\/fnana.2015.00049"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1111\/head.14740","article-title":"Glial activation in pain and emotional processing regions in the nitroglycerin mouse model of chronic migraine","volume":"64","author":"Cropper","year":"2024","journal-title":"Headache: J. Head Face Pain"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/s12974-019-1459-7","article-title":"Microglial NLRP3 inflammasome activation mediates IL-1\u03b2 release and contributes to central sensitization in a recurrent nitroglycerin-induced migraine model","volume":"16","author":"He","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"15132","DOI":"10.1038\/ncomms15132","article-title":"Neurons and neuronal activity control gene expression in astrocytes to regulate their development and metabolism","volume":"8","author":"Hasel","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/nrneurol.2014.207","article-title":"Microglial and macrophage polarization\u2014New prospects for brain repair","volume":"11","author":"Hu","year":"2015","journal-title":"Nat. Rev. Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s40478-023-01526-9","article-title":"Roles of neuropathology-associated reactive astrocytes: A systematic review","volume":"11","author":"Lawrence","year":"2023","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Shao, F., Wang, X., Wu, H., Wu, Q., and Zhang, J. (2022). Microglia and Neuroinflammation: Crucial Pathological Mechanisms in Traumatic Brain Injury-Induced Neurodegeneration. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.825086"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1038\/s41467-019-14198-8","article-title":"Identification of region-specific astrocyte subtypes at single cell resolution","volume":"11","author":"Batiuk","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1186\/s12974-024-03207-3","article-title":"Single-cell sequencing reveals glial cell involvement in development of neuropathic pain via myelin sheath lesion formation in the spinal cord","volume":"21","author":"Li","year":"2024","journal-title":"J. Neuroinflamm."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s13073-023-01257-5","article-title":"Acute ischemia induces spatially and transcriptionally distinct microglial subclusters","volume":"15","author":"Li","year":"2023","journal-title":"Genome Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1002\/ana.25169","article-title":"Activation of pial and dural macrophages and dendritic cells by cortical spreading depression","volume":"83","author":"Schain","year":"2018","journal-title":"Ann. Neurol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1177\/0333102419848122","article-title":"Investigating macrophage-mediated inflammation in migraine using ultrasmall superparamagnetic iron oxide-enhanced 3T magnetic resonance imaging","volume":"39","author":"Khan","year":"2019","journal-title":"Cephalalgia"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1016\/j.cell.2007.10.036","article-title":"The Classical Complement Cascade Mediates CNS Synapse Elimination","volume":"131","author":"Stevens","year":"2007","journal-title":"Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.cmet.2019.06.005","article-title":"A Breakdown in Metabolic Reprogramming Causes Microglia Dysfunction in Alzheimer\u2019s Disease","volume":"30","author":"Baik","year":"2019","journal-title":"Cell Metab."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.stem.2020.07.006","article-title":"A Widespread Neurogenic Potential of Neocortical Astrocytes Is Induced by Injury","volume":"27","author":"Zamboni","year":"2020","journal-title":"Cell Stem Cell"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Matusova, Z., Hol, E.M., Pekny, M., Kubista, M., and Valihrach, L. (2023). Reactive astrogliosis in the era of single-cell transcriptomics. Front. Cell. Neurosci., 17.","DOI":"10.3389\/fncel.2023.1212975"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic reactive astrocytes are induced by activated microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"106566","DOI":"10.1016\/j.phrs.2022.106566","article-title":"Targeting CSF-1R represents an effective strategy in modulating inflammatory diseases","volume":"187","author":"Xiang","year":"2023","journal-title":"Pharmacol. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1189\/jlb.0812429","article-title":"Insights into the role of progranulin in immunity, infection, and inflammation","volume":"93","author":"Jian","year":"2013","journal-title":"J. Leukoc. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/ni.2360","article-title":"IL-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia","volume":"13","author":"Wang","year":"2012","journal-title":"Nat. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.ydbio.2012.03.026","article-title":"The CSF-1 receptor ligands IL-34 and CSF-1 exhibit distinct developmental brain expression patterns and regulate neural progenitor cell maintenance and maturation","volume":"367","author":"Nandi","year":"2012","journal-title":"Dev. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1186\/s12967-023-04044-3","article-title":"CCL5\/CCR5-mediated peripheral inflammation exacerbates blood\u2013brain barrier disruption after intracerebral hemorrhage in mice","volume":"21","author":"Lin","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.gendis.2021.08.004","article-title":"CCL5\/CCR5 axis in human diseases and related treatments","volume":"9","author":"Zeng","year":"2022","journal-title":"Genes. Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"102383","DOI":"10.1016\/j.stemcr.2024.11.013","article-title":"Astrocyte-derived PTN alleviates deficits in hippocampal neurogenesis and cognition in models of multiple sclerosis","volume":"20","author":"Song","year":"2025","journal-title":"Stem Cell Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/s41392-020-00222-7","article-title":"FGF\/FGFR signaling in health and disease","volume":"5","author":"Xie","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Vila-Pueyo, M., Gliga, O., Gallardo, V.J., and Pozo-Rosich, P. (2023). The Role of Glial Cells in Different Phases of Migraine: Lessons from Preclinical Studies. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241612553"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"S44","DOI":"10.1016\/j.pain.2013.07.021","article-title":"Migraine pathophysiology: Anatomy of the trigeminovascular pathway and associated neurological symptoms, CSD, sensitization and modulation of pain","volume":"154","author":"Noseda","year":"2013","journal-title":"Pain"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.tins.2024.08.009","article-title":"Neuroimmune interactions in the development and chronification of migraine headache","volume":"47","author":"Zhang","year":"2024","journal-title":"Trends Neurosci."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/7\/942\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:01:00Z","timestamp":1760032860000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/7\/942"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,28]]},"references-count":62,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["biom15070942"],"URL":"https:\/\/doi.org\/10.3390\/biom15070942","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,28]]}}}