{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T13:42:30Z","timestamp":1791726150616,"version":"4.3.4"},"reference-count":153,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,27]],"date-time":"2022-11-27T00:00:00Z","timestamp":1669507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"New National Excellence Program of the Ministry for Culture and Innovation","award":["\u00daNKP-22-4"],"award-info":[{"award-number":["\u00daNKP-22-4"]}]},{"name":"New National Excellence Program of the Ministry for Culture and Innovation","award":["NKFIH 138125"],"award-info":[{"award-number":["NKFIH 138125"]}]},{"DOI":"10.13039\/501100018818","name":"National Research, Development and Innovation Office","doi-asserted-by":"publisher","award":["\u00daNKP-22-4"],"award-info":[{"award-number":["\u00daNKP-22-4"]}],"id":[{"id":"10.13039\/501100018818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018818","name":"National Research, Development and Innovation Office","doi-asserted-by":"publisher","award":["NKFIH 138125"],"award-info":[{"award-number":["NKFIH 138125"]}],"id":[{"id":"10.13039\/501100018818","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Migraine is a complex neurovascular disorder, which causes intense socioeconomic problems worldwide. The pathophysiology of disease is enigmatic; accordingly, therapy is not sufficient. In recent years, migraine research focused on tryptophan, which is metabolized via two main pathways, the serotonin and kynurenine pathways, both of which produce neuroactive molecules that influence pain processing and stress response by disturbing neural and brain hypersensitivity and by interacting with molecules that control vascular and inflammatory actions. Serotonin has a role in trigeminal pain processing, and melatonin, which is another product of this pathway, also has a role in these processes. One of the end products of the kynurenine pathway is kynurenic acid (KYNA), which can decrease the overexpression of migraine-related neuropeptides in experimental conditions. However, the ability of KYNA to cross the blood\u2013brain barrier is minimal, necessitating the development of synthetic analogs with potentially better pharmacokinetic properties to exploit its therapeutic potential. This review summarizes the main translational and clinical findings on tryptophan metabolism and certain neuropeptides, as well as therapeutic options that may be useful in the prevention and treatment of migraine.<\/jats:p>","DOI":"10.3390\/cells11233795","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T04:56:25Z","timestamp":1669611385000},"page":"3795","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Exploring the Tryptophan Metabolic Pathways in Migraine-Related Mechanisms"],"prefix":"10.3390","volume":"11","author":[{"given":"Tam\u00e1s","family":"K\u00f6rt\u00e9si","sequence":"first","affiliation":[{"name":"Faculty of Health Sciences and Social Studies, University of Szeged, Temesv\u00e1ri krt. 31, H-6726 Szeged, Hungary"},{"name":"ELKH-SZTE Neuroscience Research Group, University of Szeged, H-6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0888-9353","authenticated-orcid":false,"given":"Eleon\u00f3ra","family":"Spekker","sequence":"additional","affiliation":[{"name":"ELKH-SZTE Neuroscience Research Group, University of Szeged, H-6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1szl\u00f3","family":"V\u00e9csei","sequence":"additional","affiliation":[{"name":"ELKH-SZTE Neuroscience Research Group, University of Szeged, H-6725 Szeged, Hungary"},{"name":"Department of Neurology, Faculty of Medicine, Albert Szent-Gy\u00f6rgyi Clinical Center, University of Szeged, H-6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/s10194-016-0699-5","article-title":"GBD 2015: Migraine is the third cause of disability in under 50s","volume":"17","author":"Steiner","year":"2016","journal-title":"J. Headache Pain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"s15","DOI":"10.1007\/s101940170003","article-title":"Socio\u2013economic costs of migraine","volume":"2","author":"Cerbo","year":"2001","journal-title":"J. Headache Pain"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e403","DOI":"10.37765\/ajmc.2020.88547","article-title":"Estimating the Economic Burden of Migraine on US Employers","volume":"26","author":"Yucel","year":"2020","journal-title":"Am. J. Manag. Care"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Headache Classification Committee of the International Headache Society (IHS) (2013). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia, 33, 629\u2013808.","DOI":"10.1177\/0333102413485658"},{"key":"ref_5","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_6","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1177\/0333102411398152","article-title":"Tracing neural connections to pain pathways with relevance to primary headaches","volume":"31","author":"Edvinsson","year":"2011","journal-title":"Cephalalgia"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Spekker, E., Tanaka, M., Szab\u00f3, A., and V\u00e9csei, L. (2021). Neurogenic Inflammation: The Participant in Migraine and Recent Advancements in Translational Research. Biomedicines, 10.","DOI":"10.3390\/biomedicines10010076"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/jcbfm.1992.32","article-title":"The Effect of Glutamate Receptor Blockade on Anoxic Depolarization and Cortical Spreading Depression","volume":"12","author":"Lauritzen","year":"1992","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.jocn.2015.08.004","article-title":"Cortical spreading depolarization: Pathophysiology, implications, and future directions","volume":"24","author":"Kramer","year":"2016","journal-title":"J. Clin. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s13311-018-0616-5","article-title":"Glutamate and Its Receptors as Therapeutic Targets for Migraine","volume":"15","author":"Hoffmann","year":"2018","journal-title":"Neurotherapeutics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1212\/WNL.40.10.1582","article-title":"Neuroexcitatory plasma amino acids are elevated in migraine","volume":"40","author":"Ferrari","year":"1990","journal-title":"Neurology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1046\/j.1468-2982.1993.1302089.x","article-title":"Neuroexcitatory Amino Acid Levels in Plasma and Cerebrospinal Fluid During Migraine Attacks","volume":"13","author":"Castillo","year":"1993","journal-title":"Cephalalgia"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1111\/j.1468-2982.2004.00750.x","article-title":"Cerebrospinal Fluid Glutamate Levels in Chronic Migraine","volume":"24","author":"Peres","year":"2004","journal-title":"Cephalalgia"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1046\/j.1471-4159.1995.65020578.x","article-title":"Neurochemical Characterization of Extracellular Serotonin in the Rostral Ventromedial Medulla and Its Modulation by Noxious Stimuli","volume":"65","author":"Taylor","year":"1995","journal-title":"J. Neurochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3666","DOI":"10.1073\/pnas.91.9.3666","article-title":"Selective 5-HT1Da serotonin receptor gene expression in trigeminal ganglia: Implications for antimigraine drug development","volume":"91","author":"Rebeck","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1111\/j.1526-4610.2006.00528.x","article-title":"Serotonin in Trigeminal Ganglia of Female Rodents: Relevance to Menstrual Migraine","volume":"46","author":"Berman","year":"2006","journal-title":"Headache"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/S0165-6147(98)01228-0","article-title":"5-HT 1-like receptors: A time to bid goodbye","volume":"19","author":"Saxena","year":"1998","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1111\/head.12601","article-title":"Triptans in the Acute Treatment of Migraine: A Systematic Review and Network Meta-Analysis","volume":"55","author":"Cameron","year":"2015","journal-title":"Headache"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s00702-011-0665-y","article-title":"Kynurenines and headache","volume":"119","author":"Fejes","year":"2012","journal-title":"J. Neural Transm."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/nrd870","article-title":"Endogenous kynurenines as targets for drug discovery and development","volume":"1","author":"Stone","year":"2002","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/bs.acc.2019.08.005","article-title":"Tryptophan in health and disease","volume":"95","author":"Comai","year":"2020","journal-title":"Adv. Clin. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.bbrc.2017.11.203","article-title":"Low levels of serum serotonin and amino acids identified in migraine patients","volume":"496","author":"Ren","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1007\/s10072-014-1867-5","article-title":"Tryptamine levels are low in plasma of chronic migraine and chronic tension-type headache","volume":"35","author":"Bussone","year":"2014","journal-title":"Neurol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/S0022-510X(98)00023-9","article-title":"Plasma levels of neuroexcitatory amino acids in patients with migraine or tension headache","volume":"156","author":"Alam","year":"1998","journal-title":"J. Neurol. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s10194-016-0638-5","article-title":"Altered kynurenine pathway metabolites in serum of chronic migraine patients","volume":"17","author":"Curto","year":"2015","journal-title":"J. Headache Pain"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s10194-016-0620-2","article-title":"Altered serum levels of kynurenine metabolites in patients affected by cluster headache","volume":"17","author":"Curto","year":"2015","journal-title":"J. Headache Pain"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1503\/jpn.120209","article-title":"Acute tryptophan depletion in humans: A review of theoretical, practical and ethical aspects","volume":"38","author":"Young","year":"2013","journal-title":"J. Psychiatry Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1177\/0333102416640501","article-title":"Serotonergic mechanisms in the migraine brain\u2014A systematic review","volume":"37","author":"Deen","year":"2017","journal-title":"Cephalalgia"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/S0893-133X(97)00198-X","article-title":"Tryptophan Depletion During Continuous CSF Sampling in Healthy Human Subjects","volume":"19","author":"Carpenter","year":"1998","journal-title":"Neuropsychopharmacology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1046\/j.1471-4159.1999.721641.x","article-title":"Effects of acute tryptophan depletion on plasma and cerebrospinal fluid tryptophan and 5-hydroxyindoleacetic acid in normal volunteers","volume":"72","author":"Williams","year":"1999","journal-title":"J. Neurochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s00213-003-1632-6","article-title":"Effects of dietary tryptophan variations on extracellular serotonin in the dorsal hippocampus of rats","volume":"172","author":"Broersen","year":"2004","journal-title":"Psychopharmacology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1111\/j.1468-2982.2006.01212.x","article-title":"Tryptophan Depletion Increases Nausea, Headache and Photophobia in Migraine Sufferers","volume":"26","author":"Drummond","year":"2006","journal-title":"Cephalalgia"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1007\/s10072-019-03984-3","article-title":"The association between dietary tryptophan intake and migraine","volume":"40","author":"Jahromi","year":"2019","journal-title":"Neurol. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/s41598-021-04647-0","article-title":"Association of plasma tryptophan concentration with periaqueductal gray matter functional connectivity in migraine patients","volume":"12","author":"Gecse","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_35","first-page":"928","article-title":"The Role of 5-Hydroxytryptamine in the Pathophysiology of Migraine and its Relevance to the Design of Novel Treatments","volume":"17","author":"vanDenBrink","year":"2017","journal-title":"Med. Chem."},{"key":"ref_36","unstructured":"Comings, D.E. (1994). Serotonin: A Key to Migraine Disorders?. Health Fit. Mag."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1021\/cr078224o","article-title":"Serotonin Receptors","volume":"108","author":"Nichols","year":"2008","journal-title":"Chem. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1002\/hbm.20035","article-title":"Autoradiographic distribution of serotonin transporters and receptor subtypes in human brain","volume":"22","author":"Halldin","year":"2004","journal-title":"Hum. Brain Mapp."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1016\/S0028-3908(99)00010-6","article-title":"A review of central 5-HT receptors and their function","volume":"38","author":"Barnes","year":"1999","journal-title":"Neuropharmacology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1159\/000229194","article-title":"Biochemical investigations in headache: Increase in hydroxytryindoleacetic acid excretion during migraine attacks","volume":"19","author":"Sicuteri","year":"1961","journal-title":"Int. Arch. Allergy"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1001\/archneur.1967.00470230096013","article-title":"Plasma Serotonin in Migraine and Stress","volume":"16","author":"Anthony","year":"1967","journal-title":"Arch. Neurol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1093\/brain\/88.5.997","article-title":"Total plasma serotonin, 5-hydroxyindoleacetic acid and p-hydroxy-m-methoxymandelic acid excretion in normal and migrainous subjects","volume":"88","author":"Curran","year":"1965","journal-title":"Brain"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1111\/head.1967.7.3.93","article-title":"The control of cranial arteries by humoral mechanisms and its relation to the migraine syndrome","volume":"7","author":"Lance","year":"1967","journal-title":"Headache"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1212\/WNL.10.2.107","article-title":"Effect of serotonin in migraine patients","volume":"10","author":"Kimball","year":"1960","journal-title":"Neurology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1212\/WNL.39.9.1239","article-title":"Serotonin metabolism in migraine","volume":"39","author":"Ferrari","year":"1989","journal-title":"Neurology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00228-007-0391-4","article-title":"Endocannabinoids in platelets of chronic migraine patients and medication-overuse headache patients: Relation with serotonin levels","volume":"64","author":"Rossi","year":"2008","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/1742-4682-7-34","article-title":"Serotonin synthesis, release and reuptake in terminals: A mathematical model","volume":"7","author":"Best","year":"2010","journal-title":"Theor. Biol. Med. Model."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"158","DOI":"10.3389\/fendo.2019.00158","article-title":"Tryptophan Metabolic Pathways and Brain Serotonergic Activity: A Comparative Review","volume":"10","author":"Winberg","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_49","first-page":"19","article-title":"Changes in 5-hydroxytryptamine and its metabolites in neuropsychiatric disorders","volume":"17","author":"Sandler","year":"1981","journal-title":"Psychopharmacol. Bull."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/j.1365-2885.2008.00944.x","article-title":"Serotonin: A review","volume":"31","author":"Moses","year":"2008","journal-title":"J. Vet.-Pharmacol. Ther."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/0169-328X(93)90069-2","article-title":"Regional brain expression of serotonin transporter mRNA and its regulation by reuptake inhibiting antidepressants","volume":"17","author":"Lesch","year":"1993","journal-title":"Mol. Brain Res."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Mylechrane, E.J., Angus, J.A., de la Lande, I.S., and Humphrey, P.P.A. (1989). Serotoninergic Function in Neuropsychiatric Disorders. Serotonin, Macmillan Press.","DOI":"10.1007\/978-1-349-10114-6"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1007\/s00415-006-0444-0","article-title":"Increased serotonin transporter availability in the brainstem of migraineurs","volume":"254","author":"Richter","year":"2007","journal-title":"J. Neurol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1177\/0333102411420584","article-title":"Hemiplegic migraine, seizures, progressive spastic paraparesis, mood disorder, and coma in siblings with low systemic serotonin","volume":"31","author":"Horvath","year":"2011","journal-title":"Cephalalgia"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1515\/REVNEURO.1998.9.4.275","article-title":"Physiological, pathophysiological and therapeutic roles of 5-HT systems in learning and memory","volume":"9","author":"Meneses","year":"1998","journal-title":"Rev. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1111\/j.1526-4610.2010.01669.x","article-title":"The Lack of Peripheral Pathology in Migraine Headache","volume":"50","author":"Lambert","year":"2010","journal-title":"Headache"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1046\/j.1468-2982.1997.1708833.x","article-title":"Differential Distribution of 5Ht1D-and 5HT1B-Immunoreactivity within the Human Trigemino-Cerebrovascular System: Implications for the Discovery of New Antimigraine Drugs","volume":"17","author":"Longmore","year":"1997","journal-title":"Cephalalgia"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/S0006-8993(01)02645-2","article-title":"5-HT1B and 5-HT1D receptors in the human trigeminal ganglion: Co-localization with calcitonin gene-related peptide, substance P and nitric oxide synthase","volume":"909","author":"Hou","year":"2001","journal-title":"Brain Res."},{"key":"ref_59","first-page":"219","article-title":"Differential expression of sumatriptan-sensitive 5-hydroxytryptamine receptors in human trigeminal ganglia and cerebral blood vessels","volume":"50","author":"Bouchelet","year":"1996","journal-title":"Mol. Pharmacol."},{"key":"ref_60","first-page":"39","article-title":"Advances in migraine therapy\u20145-HT receptor subtype-specific agonist drugs","volume":"1","author":"Longmore","year":"1999","journal-title":"Curr. Opin. CPNS Investig. Drugs"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1111\/j.1526-4610.2004.04078.x","article-title":"Consensus Statement: Cardiovascular Safety Profile of Triptans (5-HT1B\/1D Agonists) in the Acute Treatment of Migraine","volume":"44","author":"Dodick","year":"2004","journal-title":"Headache"},{"key":"ref_62","first-page":"562","article-title":"Contractile responses to sumatriptan and ergotamine in the rabbit saphenous vein: Effect of selective 5-HT1F receptor agonists and PGF2\u03b1","volume":"131","author":"Cohen","year":"2000","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1046\/j.1468-2982.2003.00525.x","article-title":"5-HT1F Receptor Agonists in Acute Migraine Treatment: A Hypothesis","volume":"23","author":"Ramadan","year":"2003","journal-title":"Cephalalgia"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1073\/pnas.90.2.408","article-title":"Cloning of another human serotonin receptor (5-HT1F): A fifth 5-HT1 receptor subtype coupled to the inhibition of adenylate cyclase","volume":"90","author":"Adham","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1007\/s13311-018-0615-6","article-title":"Targeted 5-HT1F Therapies for Migraine","volume":"15","year":"2018","journal-title":"Neurotherapeutics"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1097\/00001756-199707070-00029","article-title":"5-HT1F receptor agonists inhibit neurogenic dural inflammation in guinea pigs","volume":"8","author":"Johnson","year":"1997","journal-title":"NeuroReport"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S0014-2999(99)00067-9","article-title":"Both 5-HT1B and 5-HT1F receptors modulate c-fos expression within rat trigeminal nucleus caudalis","volume":"369","author":"Mitsikostas","year":"1999","journal-title":"Eur. J. Pharmacol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1046\/j.1468-2982.2002.00382.x","article-title":"5-Hydroxytryptamine1B\/1D and 5-Hydroxytryptamine1FReceptors Inhibit Capsaicin-Induced C-Fos Immunoreactivity within Mouse Trigeminal Nucleus Caudalis","volume":"22","author":"Mitsikostas","year":"2002","journal-title":"Cephalalgia"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1177\/0333102410370873","article-title":"Preclinical pharmacological profile of the selective 5-HT1F receptor agonist lasmiditan","volume":"30","author":"Nelson","year":"2010","journal-title":"Cephalalgia"},{"key":"ref_70","first-page":"103","article-title":"Lasmiditan acts specifically on the 5-HT1F receptors in the central nervous system","volume":"36","author":"Kovalchin","year":"2016","journal-title":"Cephalalgia"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.pharmthera.2016.12.005","article-title":"Current and novel insights into the neurophysiology of migraine and its implications for therapeutics","volume":"172","author":"Akerman","year":"2017","journal-title":"Pharmacol. Ther."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/bs.pbr.2020.05.010","article-title":"Targeting the 5-HT1B\/1D and 5-HT1F receptors for acute migraine treatment","volume":"255","author":"Huang","year":"2020","journal-title":"Prog. Brain Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1124\/jpet.105.098269","article-title":"Evidence for a Control of Plasma Serotonin Levels by 5-Hydroxytryptamine2B Receptors in Mice","volume":"317","author":"Callebert","year":"2006","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1744-8069-4-12","article-title":"Release of Glutamate and CGRP from Trigeminal Ganglion Neurons: Role of Calcium Channels and 5-HT1 Receptor Signaling","volume":"4","author":"Xiao","year":"2008","journal-title":"Mol. Pain"},{"key":"ref_75","first-page":"346","article-title":"Integration of mitogen-activated protein kinase kinase activation in vascular 5-hydroxytryptamine2A receptor signal transduction","volume":"284","author":"Florian","year":"1998","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1046\/j.1468-2982.2001.00157.x","article-title":"Investigations into migraine pathogenesis: Time course for effects of m-CPP, BW723C86 or glyceryl trinitrate on appearance of Fos-like immunoreactivity in rat trigeminal nucleus caudalis (TNC)","volume":"21","author":"Martin","year":"2001","journal-title":"Cephalalgia"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1046\/j.1468-2982.2003.00464.x","article-title":"Neurogenic Dural Protein Extravasation Induced by Meta-Chlorophenylpiperazine (mCPP) Involves Nitric Oxide and 5-HT2B Receptor Activation","volume":"23","author":"Johnson","year":"2003","journal-title":"Cephalalgia"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.ejphar.2015.01.043","article-title":"BF-1\u2014A novel selective 5-HT2B receptor antagonist blocking neurogenic dural plasma protein extravasation in guinea pigs","volume":"751","author":"Schmitz","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1038\/clpt.1988.83","article-title":"Induction of migrainelike headaches by the serotonin agonist m-chlorophenylpiperazine","volume":"43","author":"Brewerton","year":"1988","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1046\/j.1468-2982.1998.1807421.x","article-title":"Methysergide","volume":"18","author":"Silberstein","year":"1998","journal-title":"Cephalalgia"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1111\/j.1600-079X.1996.tb00260.x","article-title":"Melatonin reduces nitric oxide synthase activity in rat hypothalamus","volume":"20","author":"Bettahi","year":"1996","journal-title":"J. Pineal Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1136\/bmj.2.5705.327","article-title":"Comparative Trial of Serotonin Antagonists in the Management of Migraine","volume":"2","author":"Lance","year":"1970","journal-title":"Br. Med. J."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1111\/j.1749-6632.2000.tb05402.x","article-title":"Melatonin and Its Relation to the Immune System and Inflammation","volume":"917","author":"Reiter","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1517\/13543784.15.4.367","article-title":"Potential therapeutic use of melatonin in migraine and other headache disorders","volume":"15","author":"Peres","year":"2006","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/s41983-022-00524-3","article-title":"Melatonin as a treatment for migraine sufferers: A systematic review","volume":"58","author":"Adnyana","year":"2022","journal-title":"Egypt. J. Neurol. Psychiatry Neurosurg."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1007\/s10753-016-0399-y","article-title":"Melatonin Alters the Mechanical and Thermal Hyperalgesia Induced by Orofacial Pain Model in Rats","volume":"39","author":"Scarabelot","year":"2016","journal-title":"Inflammation"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"359","DOI":"10.2147\/JPR.S34019","article-title":"Melatonin administration reduces inflammatory pain in rats","volume":"5","author":"Torres","year":"2012","journal-title":"J. Pain Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.neulet.2004.01.080","article-title":"Melatonin-induced inhibition of spinal cord synaptic potentiation in rats is MT2 receptor-dependent","volume":"360","author":"Noseda","year":"2004","journal-title":"Neurosci. Lett."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s40122-016-0049-y","article-title":"Melatonin in Chronic Pain Syndromes","volume":"5","author":"Danilov","year":"2016","journal-title":"Pain Ther."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2581","DOI":"10.1523\/JNEUROSCI.09-07-02581.1989","article-title":"Localization and characterization of melatonin receptors in rodent brain by in vitro autoradiography","volume":"9","author":"Weaver","year":"1989","journal-title":"J. Neurosci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1111\/j.1600-079X.1995.tb00186.x","article-title":"Melatonin receptors in the rat brain and pituitary","volume":"19","author":"Williams","year":"1995","journal-title":"J. Pineal Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S0014-2999(00)00421-0","article-title":"The analgesic effects of peripheral and central administration of melatonin in rats","volume":"403","author":"Yu","year":"2000","journal-title":"Eur. J. Pharmacol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.brainresbull.2004.09.008","article-title":"Melatonin exerts its analgesic actions not by binding to opioid receptor subtypes but by increasing the release of \u03b2-endorphin an endogenous opioid","volume":"64","author":"Shavali","year":"2005","journal-title":"Brain Res. Bull."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"167","DOI":"10.2174\/157015912800604489","article-title":"Melatonin in Antinociception: Its Therapeutic Applications","volume":"10","author":"Srinivasan","year":"2012","journal-title":"Curr. Neuropharmacol."},{"key":"ref_95","first-page":"6","article-title":"Fibromyalgia syndrome: Review of clinical presentation, pathogenesis, outcome measures, and treatment","volume":"75","author":"Mease","year":"2005","journal-title":"J. Rheumatol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s11916-007-0215-3","article-title":"Melatonin therapy in fibromyalgia","volume":"11","author":"Reiter","year":"2007","journal-title":"Curr. Pain Headache Rep."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1136\/gut.2004.062034","article-title":"Melatonin improves abdominal pain in irritable bowel syndrome patients who have sleep disturbances: A randomised, double blind, placebo controlled study","volume":"54","author":"Song","year":"2005","journal-title":"Gut"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1159\/000380912","article-title":"Short- but Not Long-Term Melatonin Administration Reduces Central Levels of Brain-Derived Neurotrophic Factor in Rats with Inflammatory Pain","volume":"22","author":"Laste","year":"2015","journal-title":"Neuroimmunomodulation"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1111\/j.1526-4610.2009.01547.x","article-title":"Urinary 6-Sulphatoxymelatonin Levels Are Depressed in Chronic Migraine and Several Comorbidities","volume":"50","author":"Masruha","year":"2010","journal-title":"Headache"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1111\/j.1526-4610.1989.hed22904242.x","article-title":"Nocturnal Plasma Melatonin Levels in Migraine: A Preliminary Report","volume":"29","author":"Claustrat","year":"1989","journal-title":"Headache"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s10194-008-0047-5","article-title":"Low urinary 6-sulphatoxymelatonin concentrations in acute migraine","volume":"9","author":"Masruha","year":"2008","journal-title":"J. Headache Pain"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1046\/j.1468-2982.1994.014003205.x","article-title":"Urinary Melatonin Excretion Throughout the Ovarian Cycle in Menstrually Related Migraine","volume":"14","author":"Murialdo","year":"1994","journal-title":"Cephalalgia"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1046\/j.1468-2982.1995.015002136.x","article-title":"Nocturnal Melatonin Excretion is Decreased in Patients with Migraine without Aura Attacks Associated with Menses","volume":"15","author":"Brun","year":"1995","journal-title":"Cephalalgia"},{"key":"ref_104","first-page":"1","article-title":"The effect of hormones and vitamin B6 on urinary excretion of metabolites of the kynurenine pathway","volume":"136","author":"Wolf","year":"1974","journal-title":"Scand. J. Clin. Lab. Investig."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/nrd3793","article-title":"Kynurenines in the CNS: Recent advances and new questions","volume":"12","author":"Toldi","year":"2013","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/nrn3257","article-title":"Kynurenines in the mammalian brain: When physiology meets pathology","volume":"13","author":"Schwarcz","year":"2012","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/S0306-4522(96)00655-0","article-title":"Protection against quinolinic acid-mediated excitotoxicity in nigrostriatal dopaminergic neurons by endogenous kynurenic acid","volume":"78","author":"Miranda","year":"1997","journal-title":"Neuroscience"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.ntt.2010.10.002","article-title":"Protective effect of l-kynurenine and probenecid on 6-hydroxydopamine-induced striatal toxicity in rats: Implications of modulating kynurenate as a protective strategy","volume":"33","year":"2011","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.neulet.2007.03.007","article-title":"Prevention of electrical stimulation-induced increase of c-fos immunoreaction in the caudal trigeminal nucleus by kynurenine combined with probenecid","volume":"418","author":"Toldi","year":"2007","journal-title":"Neurosci. Lett."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.neuropharm.2009.06.033","article-title":"l-kynurenine combined with probenecid and the novel synthetic kynurenic acid derivative attenuate nitroglycerin-induced nNOS in the rat caudal trigeminal nucleus","volume":"57","author":"Vamos","year":"2009","journal-title":"Neuropharmacology"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"981","DOI":"10.2147\/DDDT.S44496","article-title":"Unexpected effects of peripherally administered kynurenic acid on cortical spreading depression and related blood\u2013brain barrier permeability","volume":"7","author":"Toldi","year":"2013","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.expneurol.2003.12.001","article-title":"Kynurenine aminotransferase in the supratentorial dura mater of the rat: Effect of stimulation of the trigeminal ganglion","volume":"186","author":"Chadaide","year":"2004","journal-title":"Exp. Neurol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s10194-021-01229-3","article-title":"Effect of dural inflammatory soup application on activation and sensitization markers in the caudal trigeminal nucleus of the rat and the modulatory effects of sumatriptan and kynurenic acid","volume":"22","author":"Spekker","year":"2021","journal-title":"J. Headache Pain"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/S0006-8993(02)04228-2","article-title":"Kynurenic acid enhances electroacupuncture analgesia in normal and carrageenan-injected rats","volume":"966","author":"Zhang","year":"2003","journal-title":"Brain Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1213\/ane.0b013e3181b21c5e","article-title":"The Peripheral Antinociceptive Effects of Endomorphin-1 and Kynurenic Acid in the Rat Inflamed Joint Model","volume":"109","author":"Mecs","year":"2009","journal-title":"Anesthesia Analg."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.1111\/j.1471-4159.1991.tb03460.x","article-title":"Blood?Brain Barrier Transport of Kynurenines: Implications for Brain Synthesis and Metabolism","volume":"56","author":"Fukui","year":"1991","journal-title":"J. Neurochem."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1016\/j.peptides.2007.06.006","article-title":"PACAP: The road to discovery","volume":"28","author":"Arimura","year":"2007","journal-title":"Peptides"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1124\/pr.109.001370","article-title":"Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery","volume":"61","author":"Vaudry","year":"2009","journal-title":"Pharmacol. Rev."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"985","DOI":"10.2174\/138161211795589382","article-title":"PACAP is implicated in the stress axes","volume":"17","author":"Hashimoto","year":"2011","journal-title":"Curr. Pharm. Des."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"962","DOI":"10.2174\/138161211795589355","article-title":"Review on the Protective Effects of PACAP in Models of Neurodegenerative Diseases In Vitro and In Vivo","volume":"17","author":"Reglodi","year":"2011","journal-title":"Curr. Pharm. Des."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"204","DOI":"10.2174\/138161211795049679","article-title":"Protective effects of pituitary adenylate cyclase-activating polypeptide (PACAP) against apoptosis","volume":"17","author":"Seaborn","year":"2011","journal-title":"Curr. Pharm. Des."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1016\/j.bbrc.2008.03.028","article-title":"PACAP decides neuronal laminar fate via PKA signaling in the developing cerebral cortex","volume":"369","author":"Ohtsuka","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/0006-8993(95)00869-R","article-title":"Concentrations of pituitary adenylate cyclase activating polypeptide (PACAP) in human brain nuclei","volume":"699","author":"Palkovits","year":"1995","journal-title":"Brain Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1093\/brain\/awu014","article-title":"Role of PACAP in migraine headaches","volume":"137","author":"Tuka","year":"2014","journal-title":"Brain"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1016\/j.peptides.2007.04.026","article-title":"Class II G protein-coupled receptors for VIP and PACAP: Structure, models of activation and pharmacology","volume":"28","author":"Laburthe","year":"2007","journal-title":"Peptides"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1111\/gtc.12393","article-title":"Balance between cAMP and Ca2+ signals regulates expression levels of pituitary adenylate cyclase-activating polypeptide gene in neurons","volume":"21","author":"Fukuchi","year":"2016","journal-title":"Genes Cells"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"745","DOI":"10.3389\/fneur.2017.00745","article-title":"Kynurenic Acid Inhibits the Electrical Stimulation Induced Elevated Pituitary Adenylate Cyclase-Activating Polypeptide Expression in the TNC","volume":"8","author":"Tuka","year":"2018","journal-title":"Front. Neurol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.2174\/1568026619666190709092647","article-title":"Targeting the PAC1 Receptor for Neurological and Metabolic Disorders","volume":"19","author":"Liao","year":"2019","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.nbd.2011.10.010","article-title":"Pituitary adenylate cyclase-activating polypeptide plays a key role in nitroglycerol-induced trigeminovascular activation in mice","volume":"45","author":"MMarkovics","year":"2012","journal-title":"Neurobiol. Dis."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.peptides.2011.12.019","article-title":"Peripheral and central alterations of pituitary adenylate cyclase activating polypeptide-like immunoreactivity in the rat in response to activation of the trigeminovascular system","volume":"33","author":"Tuka","year":"2012","journal-title":"Peptides"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1177\/0333102413483931","article-title":"Alterations in PACAP-38-like immunoreactivity in the plasma during ictal and interictal periods of migraine patients","volume":"33","author":"Tuka","year":"2013","journal-title":"Cephalalgia"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1093\/brain\/awn307","article-title":"PACAP38 induces migraine-like attacks in patients with migraine without aura","volume":"132","author":"Schytz","year":"2009","journal-title":"Brain"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.nurt.2010.02.003","article-title":"The PACAP receptor: A novel target for migraine treatment","volume":"7","author":"Schytz","year":"2010","journal-title":"Neurotherapeutics"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1177\/0333102416639512","article-title":"Calcitonin gene-related peptide induced migraine attacks in patients with and without familial aggregation of migraine","volume":"37","author":"Guo","year":"2017","journal-title":"Cephalalgia"},{"key":"ref_135","first-page":"e1166","article-title":"Correlation of neurochemical and imaging markers in migraine: PACAP38 and DTI measures","volume":"91","author":"Tuka","year":"2018","journal-title":"Neurology"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1177\/0333102411431333","article-title":"Headache and prolonged dilatation of the middle meningeal artery by PACAP38 in healthy volunteers","volume":"32","author":"Amin","year":"2012","journal-title":"Cephalalgia"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1002\/ana.410230214","article-title":"Release of vasoactive peptides in the extracerebral circulation of humans and the cat during activation of the trigeminovascular system","volume":"23","author":"Goadsby","year":"1988","journal-title":"Ann. Neurol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.npep.2015.03.006","article-title":"Migraine and neuropeptides","volume":"52","author":"Tajti","year":"2015","journal-title":"Neuropeptides"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.expneurol.2015.05.005","article-title":"A potent and selective calcitonin gene-related peptide (CGRP) receptor antagonist, MK-8825, inhibits responses to nociceptive trigeminal activation: Role of CGRP in orofacial pain","volume":"271","author":"Pardi","year":"2015","journal-title":"Exp. Neurol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.npep.2014.01.004","article-title":"PACAP-38 but not VIP induces release of CGRP from trigeminal nucleus caudalis via a receptor distinct from the PAC1 receptor","volume":"48","author":"Baun","year":"2014","journal-title":"Neuropeptides"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.brainres.2014.11.031","article-title":"Localization of CGRP, CGRP receptor, PACAP and glutamate in trigeminal ganglion. Relation to the blood\u2013brain barrier","volume":"1600","author":"Eftekhari","year":"2015","journal-title":"Brain Res."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.brainresbull.2018.05.008","article-title":"Cerebrolysin attenuates hyperalgesia, photophobia, and neuroinflammation in a nitroglycerin-induced migraine model in rats","volume":"140","author":"Mahmoudi","year":"2018","journal-title":"Brain Res. Bull."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s10194-019-0999-7","article-title":"The effect of orofacial complete Freund\u2019s adjuvant treatment on the expression of migraine-related molecules","volume":"20","author":"Tuka","year":"2019","journal-title":"J. Headache Pain"},{"key":"ref_144","first-page":"99","article-title":"Orofacial pain management: Current perspectives","volume":"7","author":"Uyanik","year":"2014","journal-title":"J. Pain Res."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1186\/s10194-015-0581-x","article-title":"Kynurenic acid modulates experimentally induced inflammation in the trigeminal ganglion","volume":"16","author":"Edvinsson","year":"2015","journal-title":"J. Headache Pain"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s10194-017-0746-x","article-title":"Topical dura mater application of CFA induces enhanced expression of c-fos and glutamate in rat trigeminal nucleus caudalis: Attenuated by KYNA derivate (SZR72)","volume":"18","author":"Warfvinge","year":"2017","journal-title":"J. Headache Pain"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"219","DOI":"10.3389\/fnmol.2018.00219","article-title":"Transcriptional Alterations in the Trigeminal Ganglia, Nucleus and Peripheral Blood Mononuclear Cells in a Rat Orofacial Pain Model","volume":"11","author":"Kun","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s00702-016-1615-5","article-title":"A comparative assessment of two kynurenic acid analogs in the formalin model of trigeminal activation: A behavioral, immunohistochemical and pharmacokinetic study","volume":"124","author":"Veres","year":"2017","journal-title":"J. Neural Transm."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1177\/0333102415613766","article-title":"The modulatory effect of anandamide on nitroglycerin-induced sensitization in the trigeminal system of the rat","volume":"36","author":"Tar","year":"2016","journal-title":"Cephalalgia"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"4697","DOI":"10.1523\/JNEUROSCI.2200-20.2021","article-title":"PACAP Induces Light Aversion in Mice by an Inheritable Mechanism Independent of CGRP","volume":"41","author":"Kuburas","year":"2021","journal-title":"J. Neurosci."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"2450","DOI":"10.1093\/brain\/awac040","article-title":"The PACAP pathway is independent of CGRP in mouse models of migraine: Possible new drug target?","volume":"145","author":"Ernstsen","year":"2022","journal-title":"Brain"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s10194-021-01239-1","article-title":"Clinical relevance of depressed kynurenine pathway in episodic migraine patients: Potential prognostic markers in the peripheral plasma during the interictal period","volume":"22","author":"Tuka","year":"2021","journal-title":"J. Headache Pain"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"e00741","DOI":"10.1002\/prp2.741","article-title":"Phase 1 study to access safety, tolerability, pharmacokinetics, and pharmacodynamics of kynurenine in healthy volunteers","volume":"9","author":"Hansen","year":"2021","journal-title":"Pharmacol. Res. Perspect."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/23\/3795\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:27:42Z","timestamp":1760146062000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/23\/3795"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,27]]},"references-count":153,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["cells11233795"],"URL":"https:\/\/doi.org\/10.3390\/cells11233795","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,27]]}}}