{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:57:52Z","timestamp":1792789072800,"version":"4.5.0"},"reference-count":81,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T00:00:00Z","timestamp":1664496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Funding for Neuroscience Research"},{"name":"IRCCS Mondino Foundation, Pavia, Italy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Calcitonin-gene-related peptide (CGRP) plays a key role in migraine pathophysiology and more specifically in the mechanisms underlying peripheral and central sensitization. Here, we explored the interaction of CGRP with other pain mediators relevant for neuronal sensitization in an animal model of chronic migraine. Male Sprague-Dawley rats were exposed to nitroglycerin (NTG, 5 mg\/kg, i.p.) or vehicle co-administered with the CGRP receptor antagonist olcegepant (2 mg\/kg i.p.), or its vehicle, every other day over a 9-day period. Twenty-four hours after the last injection of NTG (or vehicle), behavioral test and ex vivo analysis were performed. Olcegepant attenuated NTG-induced trigeminal hyperalgesia in the second phase of the orofacial formalin test. Interestingly, it also reduced gene expression and protein levels of CGRP, pro-inflammatory cytokines, inflammatory-associated miRNAs (miR-155-5p, miR-382-5p, and miR-34a-5p), and transient receptor potential ankyrin channels in the medulla\u2013pons area, cervical spinal cord, and trigeminal ganglia. Similarly, olcegepant reduced the NTG-induced increase in CGRP and inflammatory cytokines in serum. The findings show that the activation of the CGRP pathway in a migraine animal model was associated to the persistent activation of inflammatory pathways, which was paralleled by a condition of hyperalgesia. These molecular events are relevant for informing us about the mechanisms underlying chronic migraine.<\/jats:p>","DOI":"10.3390\/cells11193092","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T01:52:21Z","timestamp":1665193941000},"page":"3092","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Antagonism of CGRP Receptor: Central and Peripheral Mechanisms and Mediators in an Animal Model of Chronic Migraine"],"prefix":"10.3390","volume":"11","author":[{"given":"Rosaria","family":"Greco","sequence":"first","affiliation":[{"name":"Unit of Translational Neurovascular Research, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8494-7773","authenticated-orcid":false,"given":"Chiara","family":"Demartini","sequence":"additional","affiliation":[{"name":"Unit of Translational Neurovascular Research, IRCCS Mondino Foundation, 27100 Pavia, Italy"},{"name":"Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Francavilla","sequence":"additional","affiliation":[{"name":"Unit of Translational Neurovascular Research, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Zanaboni","sequence":"additional","affiliation":[{"name":"Unit of Translational Neurovascular Research, IRCCS Mondino Foundation, 27100 Pavia, Italy"},{"name":"Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1513-2113","authenticated-orcid":false,"given":"Cristina","family":"Tassorelli","sequence":"additional","affiliation":[{"name":"Unit of Translational Neurovascular Research, IRCCS Mondino Foundation, 27100 Pavia, Italy"},{"name":"Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1152\/physrev.00034.2015","article-title":"Pathophysiology of Migraine: A Disorder of Sensory Processing","volume":"97","author":"Goadsby","year":"2017","journal-title":"Physiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.neurol.2021.06.003","article-title":"CGRP and migraine: From bench to bedside","volume":"177","author":"Edvinsson","year":"2021","journal-title":"Rev. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/0306-4522(88)90018-8","article-title":"Differential expression of alpha-CGRP and beta-CGRP by primary sensory neurons and enteric autonomic neurons of the rat","volume":"25","author":"Mulderry","year":"1988","journal-title":"Neuroscience"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1111\/head.13529","article-title":"CGRP and the Trigeminal System in Migraine","volume":"59","author":"Iyengar","year":"2019","journal-title":"Headache"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1002\/cne.21607","article-title":"Calcitonin receptor-like receptor (CLR), receptor activity-modifying protein 1 (RAMP1), and calcitonin gene-related peptide (CGRP) immunoreactivity in the rat trigeminovascular system: Differences between peripheral and central CGRP receptor distribution","volume":"507","author":"Lennerz","year":"2008","journal-title":"J. Comp. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.brainresrev.2004.11.006","article-title":"The role of mast cells in migraine pathophysiology","volume":"49","author":"Theoharides","year":"2005","journal-title":"Brain Res. Brain Res. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Afroz, S., Arakaki, R., Iwasa, T., Oshima, M., Hosoki, M., Inoue, M., Baba, O., Okayama, Y., and Matsuka, Y. (2019). CGRP Induces Differential Regulation of Cytokines from Satellite Glial Cells in Trigeminal Ganglia and Orofacial Nociception. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030711"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/S0197-0186(01)00094-8","article-title":"Substance P and calcitonin gene-related peptide increase IL-1 beta, IL-6 and TNF alpha secretion from human peripheral blood mononuclear cells","volume":"40","author":"Cuesta","year":"2002","journal-title":"Neurochem. Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"11193","DOI":"10.1073\/pnas.1307445110","article-title":"Fractalkine mediates inflammatory pain through activation of satellite glial cells","volume":"110","author":"Souza","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1177\/154405910708600612","article-title":"NGF up-regulates TRPA1: Implications for orofacial pain","volume":"86","author":"Diogenes","year":"2007","journal-title":"J. Dent. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"31962","DOI":"10.1074\/jbc.M112.361139","article-title":"Hypoxia-inducible factor-1\u03b1 (HIF1\u03b1) switches on transient receptor potential ankyrin repeat 1 (TRPA1) gene expression via a hypoxia response element-like motif to modulate cytokine release","volume":"287","author":"Hatano","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4381","DOI":"10.1038\/ncomms5381","article-title":"H2S and NO cooperatively regulate vascular tone by activating a neuroendocrine HNO-TRPA1-CGRP signalling pathway","volume":"5","author":"Eberhardt","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.pain.2010.08.021","article-title":"TRPA1 receptors mediate environmental irritant-induced meningeal vasodilatation","volume":"152","author":"Kunkler","year":"2011","journal-title":"Pain"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1038\/s41582-019-0216-y","article-title":"Does inflammation have a role in migraine?","volume":"15","author":"Edvinsson","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/BF02333240","article-title":"Causes and mechanisms of primary headaches: Toward a bio-behavioral model","volume":"16","author":"Buzzi","year":"1995","journal-title":"Ital. J. Neurol. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2490","DOI":"10.1093\/brain\/124.12.2490","article-title":"Delayed inflammation in rat meninges: Implications for migraine pathophysiology","volume":"124","author":"Reuter","year":"2001","journal-title":"Brain"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/nm0202-136","article-title":"Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model","volume":"8","author":"Bolay","year":"2002","journal-title":"Nat. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S1471-4892(02)00016-4","article-title":"The neuronal versus vascular hypothesis of migraine and cortical spreading depression","volume":"3","author":"Parsons","year":"2003","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e01701","DOI":"10.1002\/brb3.1701","article-title":"Gepants for abortive treatment of migraine: A network meta-analysis","volume":"10","author":"Hong","year":"2020","journal-title":"Brain Behav."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/bs.pbr.2020.06.019","article-title":"Calcitonin gene-related peptide (CGRP)-targeted therapies as preventive and acute treatments for migraine-The monoclonal antibodies and gepants","volume":"255","author":"Chiang","year":"2020","journal-title":"Prog. Brain Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1186\/s10194-021-01335-2","article-title":"CGRP monoclonal antibodies in migraine: An efficacy and tolerability comparison with standard prophylactic drugs","volume":"22","author":"Vandervorst","year":"2021","journal-title":"J. Headache Pain"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2919","DOI":"10.2174\/1381612825666190709204107","article-title":"Novelty in Inflammation and Immunomodulation in Migraine","volume":"25","author":"Cavestro","year":"2019","journal-title":"Curr. Pharm. Des."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1093\/cei\/uxab025","article-title":"Immunological findings in patients with migraine and other primary headaches: A narrative review","volume":"207","author":"Biscetti","year":"2022","journal-title":"Clin. Exp. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1152\/physrev.00006.2010","article-title":"MicroRNAs in development and disease","volume":"91","author":"Sayed","year":"2011","journal-title":"Physiol. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ahmad, L., Demartini, C., Corrado, M., Vaghi, G., Piella, E.M., Allena, M., Zanaboni, A.M., Greco, R., Tassorelli, C., and De Icco, R. (2021). Expression of Selected microRNAs in Migraine: A New Class of Possible Biomarkers of Disease?. Processes, 9.","DOI":"10.3390\/pr9122199"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s10194-020-01189-0","article-title":"Plasma levels of CGRP and expression of specific microRNAs in blood cells of episodic and chronic migraine subjects: Towards the identification of a panel of peripheral biomarkers of migraine?","volume":"21","author":"Greco","year":"2020","journal-title":"J. Headache Pain"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9367","DOI":"10.3892\/mmr.2017.7779","article-title":"Calcitonin gene-related peptide induces IL-6 expression in RAW264.7 macrophages mediated by mmu_circRNA_007893","volume":"16","author":"Deng","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1186\/s10194-015-0560-2","article-title":"Evaluation of ADMA-DDAH-NOS axis in specific brain areas following nitroglycerin administration: Study in an animal model of migraine","volume":"16","author":"Greco","year":"2015","journal-title":"J. Headache Pain"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"105157","DOI":"10.1016\/j.nbd.2020.105157","article-title":"Characterization of the peripheral FAAH inhibitor, URB937, in animal models of acute and chronic migraine","volume":"147","author":"Greco","year":"2021","journal-title":"Neurobiol. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s10194-019-1043-7","article-title":"Animal models of migraine and experimental techniques used to examine trigeminal sensory processing","volume":"20","author":"Harriott","year":"2019","journal-title":"J. Headache Pain"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/0304-3959(83)90201-4","article-title":"Ethical guidelines for investigations of experimental pain in conscious animals","volume":"16","author":"Zimmermann","year":"1983","journal-title":"Pain"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1177\/0333102413502735","article-title":"Nitric oxide synthase, calcitonin gene-related peptide and NK-1 receptor mechanisms are involved in GTN-induced neuronal activation","volume":"34","author":"Ramachandran","year":"2014","journal-title":"Cephalalgia"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1038\/s41598-018-19901-1","article-title":"A unique inbred rat strain with sustained cephalic hypersensitivity as a model of chronic migraine-like pain","volume":"8","author":"Munro","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1097\/j.pain.0000000000002142","article-title":"Therapeutic targeting of nitroglycerin-mediated trigeminovascular neuronal hypersensitivity predicts clinical outcomes of migraine abortives","volume":"162","author":"Akerman","year":"2021","journal-title":"Pain"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"104624","DOI":"10.1016\/j.nbd.2019.104624","article-title":"FAAH inhibition as a preventive treatment for migraine: A pre-clinical study","volume":"134","author":"Greco","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1046\/j.1468-2982.2001.00140.x","article-title":"Neuropeptide localization in the \u201cmigraine generator\u201d region of the human brainstem","volume":"21","author":"Tajti","year":"2001","journal-title":"Cephalalgia"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1097\/j.pain.0000000000001421","article-title":"Divergent influences of the locus coeruleus on migraine pathophysiology","volume":"160","author":"Strother","year":"2019","journal-title":"Pain"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1177\/0333102416678000","article-title":"Effects of kynurenic acid analogue 1 (KYNA-A1) in nitroglycerin-induced hyperalgesia: Targets and anti-migraine mechanisms","volume":"37","author":"Greco","year":"2017","journal-title":"Cephalalgia"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s10194-021-01374-9","article-title":"IL-17 crosses the blood-brain barrier to trigger neuroinflammation: A novel mechanism in nitroglycerin-induced chronic migraine","volume":"23","author":"Chen","year":"2022","journal-title":"J. Headache Pain"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.neulet.2014.12.021","article-title":"Effects of rizatriptan on the expression of calcitonin gene-related peptide and cholecystokinin in the periaqueductal gray of a rat migraine model","volume":"587","author":"Yao","year":"2015","journal-title":"Neurosci. Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"254","DOI":"10.2174\/157015908785777193","article-title":"Functional neuroanatomy of the noradrenergic locus coeruleus: Its roles in the regulation of arousal and autonomic function part II: Physiological and pharmacological manipulations and pathological alterations of locus coeruleus activity in humans","volume":"6","author":"Samuels","year":"2008","journal-title":"Curr. Neuropharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.neuron.2015.07.002","article-title":"CRH Engagement of the Locus Coeruleus Noradrenergic System Mediates Stress-Induced Anxiety","volume":"87","author":"McCall","year":"2015","journal-title":"Neuron"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.neuroscience.2016.05.057","article-title":"Noradrenergic Locus Coeruleus pathways in pain modulation","volume":"338","author":"Borges","year":"2016","journal-title":"Neuroscience"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1002\/ana.410280213","article-title":"Vasoactive peptide release in the extracerebral circulation of humans during migraine headache","volume":"28","author":"Goadsby","year":"1990","journal-title":"Ann. Neurol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.pain.2003.09.008","article-title":"NO-induced migraine attack: Strong increase in plasma calcitonin gene-related peptide (CGRP) concentration and negative correlation with platelet serotonin release","volume":"106","author":"Juhasz","year":"2003","journal-title":"Pain"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/j.1468-2982.2005.00836.x","article-title":"Sumatriptan causes parallel decrease in plasma calcitonin gene-related peptide (CGRP) concentration and migraine headache during nitroglycerin induced migraine attack","volume":"25","author":"Juhasz","year":"2005","journal-title":"Cephalalgia"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2468","DOI":"10.1523\/JNEUROSCI.08-07-02468.1988","article-title":"Enrichment of a vasoactive neuropeptide (calcitonin gene related peptide) in the trigeminal sensory projection to the intracranial arteries","volume":"8","year":"1988","journal-title":"J. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e36","DOI":"10.1017\/S1462399411002067","article-title":"Calcitonin gene-related peptide in migraine: Intersection of peripheral inflammation and central modulation","volume":"13","author":"Raddant","year":"2011","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/s10194-017-0804-4","article-title":"The role of the transient receptor potential ankyrin type-1 (TRPA1) channel in migraine pain: Evaluation in an animal model","volume":"18","author":"Demartini","year":"2017","journal-title":"J. Headache Pain"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00726-011-1161-2","article-title":"Modulation of immune responses by the neuropeptide CGRP","volume":"45","author":"Holzmann","year":"2013","journal-title":"Amino. Acids"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"277","DOI":"10.4103\/aian.AIAN_371_18","article-title":"Association of Serum Levels of Calcitonin Gene-related Peptide and Cytokines during Migraine Attacks","volume":"22","author":"Han","year":"2019","journal-title":"Ann. Indian Acad. Neurol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.ejphar.2018.12.004","article-title":"Progression in migraine: Role of mast cells and pro-inflammatory and anti-inflammatory cytokines","volume":"844","author":"Conti","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/1744-8069-7-94","article-title":"Calcitonin gene-related peptide promotes cellular changes in trigeminal neurons and glia implicated in peripheral and central sensitization","volume":"7","author":"Cady","year":"2011","journal-title":"Mol. Pain"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.neulet.2010.01.074","article-title":"Calcitonin gene-related peptide differentially regulates gene and protein expression in trigeminal glia cells: Findings from array analysis","volume":"473","author":"Vause","year":"2010","journal-title":"Neurosci. Lett."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3638","DOI":"10.1523\/JNEUROSCI.6440-10.2011","article-title":"Calcitonin gene-related peptide-mediated enhancement of purinergic neuron\/glia communication by the algogenic factor bradykinin in mouse trigeminal ganglia from wild-type and R192Q Cav2.1 Knock-in mice: Implications for basic mechanisms of migraine pain","volume":"31","author":"Ceruti","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.pharep.2019.02.015","article-title":"Effect of TRPA1 activator allyl isothiocyanate (AITC) on rat dural and pial arteries","volume":"71","author":"Hansted","year":"2019","journal-title":"Pharmacol. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1093\/brain\/awr272","article-title":"The \u2018headache tree\u2019 via umbellulone and TRPA1 activates the trigeminovascular system","volume":"135","author":"Nassini","year":"2012","journal-title":"Brain"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"15294","DOI":"10.1523\/JNEUROSCI.0921-11.2011","article-title":"Change in microRNAs associated with neuronal adaptive responses in the nucleus accumbens under neuropathic pain","volume":"31","author":"Imai","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1177\/0333102417742375","article-title":"Elevated circulating endothelial-specific microRNAs in migraine patients: A pilot study","volume":"38","author":"Cheng","year":"2018","journal-title":"Cephalalgia"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1186\/s12974-021-02342-5","article-title":"MicroRNA-155-5p promotes neuroinflammation and central sensitization via inhibiting SIRT1 in a nitroglycerin-induced chronic migraine mouse model","volume":"18","author":"Wen","year":"2021","journal-title":"J. Neuroinflammation"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1007\/s12035-015-9106-5","article-title":"Serum MicroRNA Signatures in Migraineurs During Attacks and in Pain-Free Periods","volume":"53","author":"Andersen","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1002\/ana.10159","article-title":"Nuclear factor-kappaB as a molecular target for migraine therapy","volume":"51","author":"Reuter","year":"2002","journal-title":"Ann. Neurol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.neuro.2005.02.005","article-title":"Activation of the transcription factor NF-kappaB in the nucleus trigeminalis caudalis in an animal model of migraine","volume":"26","author":"Greco","year":"2005","journal-title":"Neurotoxicology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1111\/j.1468-2982.2006.01164.x","article-title":"NF-\u03baB activity and iNOS expression in monocytes from internal jugular blood of migraine without aura patients during attacks","volume":"26","author":"Sarchielli","year":"2006","journal-title":"Cephalalgia"},{"key":"ref_65","first-page":"2022","article-title":"MiR-30a relieves migraine by degrading CALCA","volume":"22","author":"Zhai","year":"2018","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"468","DOI":"10.3109\/07853890.2015.1071871","article-title":"MicroRNA profiling in migraine without aura: Pilot study","volume":"47","author":"Tafuri","year":"2015","journal-title":"Ann. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1177\/0333102420942230","article-title":"Neurophysiological and biomolecular effects of erenumab in chronic migraine: An open label study","volume":"40","author":"Fiamingo","year":"2020","journal-title":"Cephalalgia"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"11193","DOI":"10.1073\/pnas.1019536108","article-title":"MicroRNA-155 as a proinflammatory regulator in clinical and experimental arthritis","volume":"108","author":"Alivernini","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2056","DOI":"10.1093\/rheumatology\/kew272","article-title":"MicroRNA-155 regulates monocyte chemokine and chemokine receptor expression in Rheumatoid Arthritis","volume":"55","author":"Elmesmari","year":"2016","journal-title":"Rheumatology"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/s10194-016-0696-8","article-title":"Risk of medication overuse headache across classes of treatments for acute migraine","volume":"17","author":"Thorlund","year":"2016","journal-title":"J. Headache Pain"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2681","DOI":"10.1093\/brain\/awaa211","article-title":"Differential medication overuse risk of novel anti-migraine therapeutics","volume":"143","author":"Saengjaroentham","year":"2020","journal-title":"Brain"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1177\/0333102420938652","article-title":"Ubrogepant does not induce latent sensitization in a preclinical model of medication overuse headache","volume":"40","author":"Navratilova","year":"2020","journal-title":"Cephalalgia"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e2309","DOI":"10.1212\/WNL.0000000000007497","article-title":"Erenumab in chronic migraine with medication overuse: Subgroup analysis of a randomized trial","volume":"92","author":"Tepper","year":"2019","journal-title":"Neurology"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Moreno-Ajona, D., Villar-Mart\u00ednez, M.D., and Goadsby, P.J. (2022). New Generation Gepants: Migraine Acute and Preventive Medications. J. Clin. Med., 11.","DOI":"10.3390\/jcm11061656"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1056\/NEJMoa030505","article-title":"Calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine","volume":"350","author":"Olesen","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1177\/0333102420963857","article-title":"No additive effect of combining sumatriptan and olcegepant in the GTN mouse model of migraine","volume":"41","author":"Ernstsen","year":"2021","journal-title":"Cephalalgia"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1177\/0333102410363491","article-title":"CGRP receptor antagonist olcegepant (BIBN4096BS) does not prevent glyceryl trinitrate-induced migraine","volume":"30","author":"Tvedskov","year":"2010","journal-title":"Cephalalgia"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1177\/0333102417736900","article-title":"Recognizing the role of CGRP and CGRP receptors in migraine and its treatment","volume":"39","author":"Edvinsson","year":"2019","journal-title":"Cephalalgia"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1177\/0333102420914913","article-title":"No central action of CGRP antagonising drugs in the GTN mouse model of migraine","volume":"40","author":"Christensen","year":"2020","journal-title":"Cephalalgia"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3134","DOI":"10.1093\/brain\/awp168","article-title":"Calcitonin gene-related peptide receptor antagonist olcegepant acts in the spinal trigeminal nucleus","volume":"132","author":"Sixt","year":"2009","journal-title":"Brain"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s10194-019-1070-4","article-title":"Microglia P2X4R-BDNF signalling contributes to central sensitization in a recurrent nitroglycerin-induced chronic migraine model","volume":"21","author":"Long","year":"2020","journal-title":"J. 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