{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:35:34Z","timestamp":1792787734072,"version":"4.5.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":86,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Henan Provincial Department of Science and Technology Research Project","award":["No. 242102310078"],"award-info":[{"award-number":["No. 242102310078"]}],"id":[{"id":"https:\/\/ror.org\/03rbw2w25","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Headache Pain"],"DOI":"10.1186\/s10194-026-02426-8","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T14:14:59Z","timestamp":1783433699000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Peptidomics profiling identifies endogenous peptides associated with meningeal afferent activation in a chronic migraine mouse model"],"prefix":"10.1186","volume":"27","author":[{"given":"Guizeng","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyang","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongkun","family":"Gui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuzhi","family":"Zang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhitao","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenguang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junwei","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingmin","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"2426_CR1","doi-asserted-by":"publisher","unstructured":"Ashraf U, Goadsby PJ (2025) Migraine: advances in treatment. Trends Molecular Med https:\/\/doi.org\/10.1016\/j.molmed.2025.08.009","DOI":"10.1016\/j.molmed.2025.08.009"},{"key":"2426_CR2","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1016\/S1474-4422(22)00211-3","volume":"21","author":"EK Seng","year":"2022","unstructured":"Seng EK, Martin PR, Houle TT (2022) Lifestyle factors and migraine. Lancet Neurol 21:911\u2013921","journal-title":"Lancet Neurol"},{"key":"2426_CR3","doi-asserted-by":"publisher","first-page":"333102425137262","DOI":"10.1177\/03331024251372621","volume":"45","author":"M Viana","year":"2025","unstructured":"Viana M, Peres MFP (2025) The spectrum of migraine aura: Towards a precise phenotypic classification. Cephalalgia: Int J headache 45:3331024251372621","journal-title":"Cephalalgia: Int J headache"},{"key":"2426_CR4","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1186\/s10194-024-01889-x","volume":"25","author":"A Raggi","year":"2024","unstructured":"Raggi A et al (2024) Hallmarks of primary headache: part 1 - migraine. J Headache Pain 25:189","journal-title":"J Headache Pain"},{"key":"2426_CR5","doi-asserted-by":"publisher","first-page":"e00833","DOI":"10.1016\/j.neurot.2026.e00833","volume":"23","author":"A Della Pietra","year":"2026","unstructured":"Della Pietra A, Russo AF (2026) Overlapping pathways of migraine and the endocannabinoid system: Potential therapeutic targets. Neurotherapeutics 23:e00833","journal-title":"Neurotherapeutics"},{"key":"2426_CR6","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1016\/S1474-4422(19)30185-1","volume":"18","author":"M Ashina","year":"2019","unstructured":"Ashina M et al (2019) Migraine and the trigeminovascular system-40 years and counting. Lancet Neurol 18:795\u2013804","journal-title":"Lancet Neurol"},{"key":"2426_CR7","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1146\/annurev-neuro-080422-105509","volume":"46","author":"D Levy","year":"2023","unstructured":"Levy D, Moskowitz MA (2023) Meningeal Mechanisms and the Migraine Connection. Annu Rev Neurosci 46:39\u201358","journal-title":"Annu Rev Neurosci"},{"key":"2426_CR8","doi-asserted-by":"crossref","unstructured":"Krivoshein G et al (2022) Activation of meningeal afferents relevant to trigeminal headache pain after photothrombotic stroke lesion: a pilot study in mice. Int J Mol Sci 23","DOI":"10.3390\/ijms232012590"},{"key":"2426_CR9","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s10194-021-01383-8","volume":"23","author":"G Krivoshein","year":"2022","unstructured":"Krivoshein G, Tolner EA, Maagdenberg AVD, Giniatullin RA (2022) Migraine-relevant sex-dependent activation of mouse meningeal afferents by TRPM3 agonists. J Headache Pain 23:4","journal-title":"J Headache Pain"},{"key":"2426_CR10","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s10194-025-01959-8","volume":"26","author":"L Pellesi","year":"2025","unstructured":"Pellesi L, Edvinsson L (2025) Revisiting substance P in migraine: a methodological approach inspired by anti-CGRP and anti-PACAP success. J Headache Pain 26:22","journal-title":"J Headache Pain"},{"key":"2426_CR11","doi-asserted-by":"publisher","first-page":"333102425136424","DOI":"10.1177\/03331024251364242","volume":"45","author":"AD Pietra","year":"2025","unstructured":"Pietra AD, Kuburas A, Russo AF (2025) PACAP versus CGRP in migraine: From mouse models to clinical translation. Cephalalgia: Int J headache 45:3331024251364242","journal-title":"Cephalalgia: Int J headache"},{"key":"2426_CR12","doi-asserted-by":"crossref","unstructured":"Liu Y, Wang W, Pellesi L Headache mechanisms: what we still do not know. Brain Conflux 1:e220","DOI":"10.71321\/h9jhnr48"},{"key":"2426_CR13","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1186\/s10194-025-02058-4","volume":"26","author":"G Guo","year":"2025","unstructured":"Guo G et al (2025) Fibroblast reprogramming in the dura mater of NTG-induced migraine-related chronic hypersensitivity model drives monocyte infiltration via Angptl1-dependent stromal signaling. J Headache Pain 26:130","journal-title":"J Headache Pain"},{"key":"2426_CR14","doi-asserted-by":"publisher","first-page":"333102425136875","DOI":"10.1177\/03331024251368757","volume":"45","author":"MP Johnson","year":"2025","unstructured":"Johnson MP et al (2025) Preclinical and clinical evaluation of LY3451838, a PACAP-neutralizing monoclonal antibody, in randomized, double-blind, placebo-controlled phase 1 and phase 2 studies involving healthy adults and adults with treatment-resistant migraine. Cephalalgia: Int J headache 45:3331024251368757","journal-title":"Cephalalgia: Int J headache"},{"key":"2426_CR15","doi-asserted-by":"publisher","first-page":"1654","DOI":"10.1002\/acn3.52119","volume":"11","author":"N Karsan","year":"2024","unstructured":"Karsan N, Edvinsson L, Vecsei L, Goadsby PJ (2024) Pituitary cyclase-activating polypeptide targeted treatments for the treatment of primary headache disorders. Ann Clin Transl Neurol 11:1654\u20131668","journal-title":"Ann Clin Transl Neurol"},{"key":"2426_CR16","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1186\/s10194-025-02105-0","volume":"26","author":"R Arquizan","year":"2025","unstructured":"Arquizan R et al (2025) Vascular responses to molecular migraine triggers: a systematic review of magnetic resonance angiography studies. J Headache Pain 26:181","journal-title":"J Headache Pain"},{"key":"2426_CR17","doi-asserted-by":"publisher","first-page":"991403","DOI":"10.3389\/fnana.2022.991403","volume":"16","author":"AM Lund","year":"2022","unstructured":"Lund AM, Hannibal J (2022) Localization of the neuropeptides pituitary adenylate cyclase-activating polypeptide, vasoactive intestinal peptide, and their receptors in the basal brain blood vessels and trigeminal ganglion of the mouse CNS; an immunohistochemical study. Front Neuroanat 16:991403","journal-title":"Front Neuroanat"},{"key":"2426_CR18","doi-asserted-by":"publisher","first-page":"120424","DOI":"10.1016\/j.jep.2025.120424","volume":"353","author":"W Wen","year":"2025","unstructured":"Wen W et al (2025) Blockade of interleukin-17A contributes to a novel mechanism by which casticin relieves chronic migraine. J Ethnopharmacol 353:120424","journal-title":"J Ethnopharmacol"},{"key":"2426_CR19","doi-asserted-by":"publisher","first-page":"114","DOI":"10.3389\/fncel.2019.00114","volume":"13","author":"SH Pedersen","year":"2019","unstructured":"Pedersen SH et al (2019) PACAP-38 and PACAP(6\u201338) Degranulate Rat Meningeal Mast Cells via the Orphan MrgB(3)-Receptor. Front Cell Neurosci 13:114","journal-title":"Front Cell Neurosci"},{"key":"2426_CR20","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-025-02187-z","author":"A Mudgal","year":"2025","unstructured":"Mudgal A et al (2025) Ro 64-6198, a selective NOP receptor agonist attenuates social impairments associated with NTG-induced migraine pain. Neuropsychopharmacology: official publication Am Coll Neuropsychopharmacol. https:\/\/doi.org\/10.1038\/s41386-025-02187-z","journal-title":"Neuropsychopharmacology: official publication Am Coll Neuropsychopharmacol"},{"key":"2426_CR21","doi-asserted-by":"publisher","first-page":"4274","DOI":"10.1093\/brain\/awad191","volume":"146","author":"S Ryu","year":"2023","unstructured":"Ryu S et al (2023) Peripheral CCL2-CCR2 signalling contributes to chronic headache-related sensitization. Brain 146:4274\u20134291","journal-title":"Brain"},{"key":"2426_CR22","doi-asserted-by":"crossref","unstructured":"Leff-Gelman P, Pell\u00f3n-D\u00edaz G, Camacho-Arroyo I, Palomera-Garfias N, Flores-Ramos M (2025) Neuroendocrine regulation and neural circuitry of parenthood: integrating neuropeptides, brain receptors, and maternal behavior. Int J Mol Sci 26","DOI":"10.3390\/ijms26189007"},{"key":"2426_CR23","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1038\/s41582-024-01011-4","volume":"20","author":"H Ashina","year":"2024","unstructured":"Ashina H et al (2024) Pituitary adenylate cyclase-activating polypeptide signalling as a therapeutic target in migraine. Nat reviews Neurol 20:660\u2013670","journal-title":"Nat reviews Neurol"},{"key":"2426_CR24","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1056\/NEJMoa2314577","volume":"391","author":"M Ashina","year":"2024","unstructured":"Ashina M, Phul R, Khodaie M, L\u00f6f E, Florea I (2024) A Monoclonal Antibody to PACAP for Migraine Prevention. N Engl J Med 391:800\u2013809","journal-title":"N Engl J Med"},{"key":"2426_CR25","doi-asserted-by":"publisher","first-page":"e70090","DOI":"10.1111\/adb.70090","volume":"30","author":"S Bose","year":"2025","unstructured":"Bose S et al (2025) PACAP Signalling Network in the Nucleus Accumbens Core Regulates Reinstatement Behaviour in Rat. Addict Biol 30:e70090","journal-title":"Addict Biol"},{"key":"2426_CR26","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1186\/s10194-024-01925-w","volume":"25","author":"L Pellesi","year":"2024","unstructured":"Pellesi L et al (2024) Combining treatments for migraine prophylaxis: the state-of-the-art. J Headache Pain 25:214","journal-title":"J Headache Pain"},{"key":"2426_CR27","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaf284","author":"RH Christensen","year":"2025","unstructured":"Christensen RH, Strassman A, Ashina M, Ashina H, Burstein R (2025) Activation and sensitization of meningeal nociceptors by PACAP-38: implications for migraine headache. Brain. https:\/\/doi.org\/10.1093\/brain\/awaf284","journal-title":"Brain"},{"key":"2426_CR28","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1186\/s10194-024-01830-2","volume":"25","author":"S Guo","year":"2024","unstructured":"Guo S et al (2024) VPAC1 and VPAC2 receptors mediate tactile hindpaw hypersensitivity and carotid artery dilatation induced by PACAP38 in a migraine relevant mouse model. J Headache Pain 25:126","journal-title":"J Headache Pain"},{"key":"2426_CR29","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-025-01128-0","author":"AM Harriott","year":"2025","unstructured":"Harriott AM, Ayata C (2025) Spreading depolarization as a therapeutic target in migraine. Nat reviews Neurol. https:\/\/doi.org\/10.1038\/s41582-025-01128-0","journal-title":"Nat reviews Neurol"},{"key":"2426_CR30","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1159\/000542984","volume":"115","author":"D Lorincz","year":"2025","unstructured":"Lorincz D, Drury HR, Lim R, Brichta AM (2025) Immunohistochemical Identification of Sensory Neuropeptides Calcitonin Gene-Related Peptide, Substance P, and Pituitary Adenylate Cyclase-Activating Polypeptide in Efferent Vestibular Nucleus Neurons. Neuroendocrinology 115:269\u2013282","journal-title":"Neuroendocrinology"},{"key":"2426_CR31","doi-asserted-by":"publisher","first-page":"e2500765","DOI":"10.1002\/adhm.202500765","volume":"14","author":"E Ho","year":"2025","unstructured":"Ho E et al (2025) Immunomodulation With Local, Sustained Delivery of Pituitary Adenylate Cyclase Activating Polypeptide Results in Improved Functional Recovery in Stroke-Injured Mice. Adv Healthc Mater 14:e2500765","journal-title":"Adv Healthc Mater"},{"key":"2426_CR32","doi-asserted-by":"publisher","first-page":"2646","DOI":"10.1093\/brain\/awaf131","volume":"148","author":"HC Diener","year":"2025","unstructured":"Diener HC (2025) PACAP and migraine. Brain 148:2646\u20132649","journal-title":"Brain"},{"key":"2426_CR33","doi-asserted-by":"crossref","unstructured":"Tasma Z, Hay DL, Decoding PACAP (2025) Signaling: splice variants, pathways and designer drugs. Cephalalgia 45:3331024251363560","DOI":"10.1177\/03331024251363560"},{"key":"2426_CR34","doi-asserted-by":"publisher","first-page":"154","DOI":"10.4103\/bc.bc_95_23","volume":"10","author":"J Luo","year":"2024","unstructured":"Luo J et al (2024) Restoring brain health: Electroacupuncture at GB20 and LR3 for migraine mitigation through mitochondrial restoration. Brain circulation 10:154\u2013161","journal-title":"Brain circulation"},{"key":"2426_CR35","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1111\/bph.17424","volume":"182","author":"E Mangutov","year":"2025","unstructured":"Mangutov E et al (2025) Activation of \u03b4-opioid receptors blocks allodynia in a model of headache induced by PACAP. Br J Pharmacol 182:1630\u20131643","journal-title":"Br J Pharmacol"},{"key":"2426_CR36","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1007\/s12325-025-03166-y","volume":"42","author":"L Pellesi","year":"2025","unstructured":"Pellesi L et al (2025) Beyond Migraine to Cluster, Menstrual, and Post-traumatic Headaches. Adv therapy 42:2078\u20132088Targeting PACAP","journal-title":"Adv therapy"},{"key":"2426_CR37","doi-asserted-by":"publisher","first-page":"176667","DOI":"10.1016\/j.ejphar.2024.176667","volume":"976","author":"HA Ruby","year":"2024","unstructured":"Ruby HA, Sayed RH, Khattab MA, Sallam NA, Kenway SA (2024) Fenofibrate ameliorates nitroglycerin-induced migraine in rats: Role of CGRP\/p-CREB\/P2X3 and NGF\/PKC\/ASIC3 signaling pathways. Eur J Pharmacol 976:176667","journal-title":"Eur J Pharmacol"},{"key":"2426_CR38","doi-asserted-by":"crossref","unstructured":"Hu S et al (2025) Single-nucleus transcriptomics reveals glial metabolic-immune rewiring and intercellular signaling disruption in chronic migraine. Biomolecules 15","DOI":"10.3390\/biom15070942"},{"key":"2426_CR39","doi-asserted-by":"crossref","unstructured":"Tanaka M et al (2023) From CGRP to PACAP, VIP, and beyond: unraveling the next chapters in migraine treatment. Cells 12","DOI":"10.3390\/cells12222649"},{"key":"2426_CR40","doi-asserted-by":"publisher","first-page":"12302","DOI":"10.1038\/s41598-023-39571-y","volume":"13","author":"S Sbei","year":"2023","unstructured":"Sbei S, Moncrief T, Limjunyawong N, Zeng Y, Green DP (2023) PACAP activates MRGPRX2 on meningeal mast cells to drive migraine-like pain. Sci Rep 13:12302","journal-title":"Sci Rep"},{"key":"2426_CR41","doi-asserted-by":"publisher","unstructured":"Shintani Y et al (2025) Rapid and long-lasting antidepressant-like effects of the pituitary adenylate cyclase-activating polypeptide receptor antagonist PA-915 in chronic stress mouse models. Molecular Psychiatry https:\/\/doi.org\/10.1038\/s41380-025-03209-4","DOI":"10.1038\/s41380-025-03209-4"},{"issue":"1177\/0972753125","key":"2426_CR42","doi-asserted-by":"publisher","first-page":"097275312513401","DOI":"10.1177\/09727531251340156","volume":"10","author":"N Sreevani","year":"2025","unstructured":"Sreevani N, Ramesh B, Maheshkumar K, Thanalakshmi J (2025) Comparative analysis of CGRP, VIP and PACAP-38 levels in migraine with and without aura: a case-control study. Ann Neurosci https:\/\/doi.org\/10.1177\/09727531251340156","journal-title":"Annals neurosciences"},{"key":"2426_CR43","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1186\/s10194-024-01804-4","volume":"25","author":"E Storch","year":"2024","unstructured":"Storch E et al (2024) PACAP-38 and sex hormones in women with migraine: exploratory analysis of a cross-sectional, matched cohort study. J Headache Pain 25:98","journal-title":"J Headache Pain"}],"container-title":["The Journal of Headache and Pain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s10194-026-02426-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s10194-026-02426-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s10194-026-02426-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:05:24Z","timestamp":1790863524000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s10194-026-02426-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,7]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["2426"],"URL":"https:\/\/doi.org\/10.1186\/s10194-026-02426-8","relation":{},"ISSN":["1129-2377"],"issn-type":[{"value":"1129-2377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,7]]},"assertion":[{"value":"22 April 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All experimental procedures involving animals were conducted in strict compliance with institutional guidelines and were approved by the Animal Ethics Committee of The First Affiliated Hospital of Henan Medical University (Approval No: EC-025-615).","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This manuscript does not include details, images, or videos relating to an individual person; therefore, consent for publication is not needed beyond the informed consent provided by all study participants as described above.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"229"}}