{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:36:19Z","timestamp":1792787779834,"version":"4.5.0"},"reference-count":83,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":90,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Key Discipline Construction Project of Traditional Chinese Medicine of Guangdong Province","award":["No. 20220105"],"award-info":[{"award-number":["No. 20220105"]}]},{"name":"National Natural Science Foundation of China","award":["No. 82405378"],"award-info":[{"award-number":["No. 82405378"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"China Postdoctoral Science Foundation","award":["No. 2024M761351"],"award-info":[{"award-number":["No. 2024M761351"]}],"id":[{"id":"https:\/\/ror.org\/0426zh255","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Major and Refractory Disease Clinical Collaboration Program of Integrated Traditional Chinese and Western Medicine","award":["ZDYN-2024-A-120"],"award-info":[{"award-number":["ZDYN-2024-A-120"]}]},{"name":"Guangdong Basic and Applied Basic Research Foundation","award":["No. 2023A1515220030"],"award-info":[{"award-number":["No. 2023A1515220030"]}]},{"name":"The second national famous Traditional Chinese Medicine Inheritance Studio","award":["No. G724290126"],"award-info":[{"award-number":["No. G724290126"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Headache Pain"],"DOI":"10.1186\/s10194-026-02457-1","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T10:16:53Z","timestamp":1784283413000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["IRAK-M attenuates pain hypersensitivity and anxiety-like behaviors in a nitroglycerin-induced chronic migraine mouse model with concomitant reductions in microglial activation and neuroinflammation"],"prefix":"10.1186","volume":"27","author":[{"given":"Xiao-Tao","family":"Liang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-Ru","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi-Mao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Yu","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Fan","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Yong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Heng","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Yan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue-Wen","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Shan","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3218-7231","authenticated-orcid":false,"given":"Wei","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"2457_CR1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/s41572-021-00328-4","volume":"8","author":"MD Ferrari","year":"2022","unstructured":"Ferrari MD, Goadsby PJ, Burstein R, Kurth T, Ayata C, Charles A, Ashina M, van den Maagdenberg AMJM, Dodick DW (2022) Migraine. Nat Rev Dis Primers 8:2","journal-title":"Nat Rev Dis Primers"},{"key":"2457_CR2","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1016\/S0140-6736(20)32160-7","volume":"397","author":"M Ashina","year":"2021","unstructured":"Ashina M, Katsarava Z, Do TP, Buse DC, Pozo-Rosich P, Ozge A, Krymchantowski AV, Lebedeva ER, Ravishankar K, Yu S et al (2021) Migraine: epidemiology and systems of care. Lancet 397:1485\u20131495","journal-title":"Lancet"},{"key":"2457_CR3","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1038\/nrneurol.2016.93","volume":"12","author":"A May","year":"2016","unstructured":"May A, Schulte LH (2016) Chronic migraine: risk factors, mechanisms and treatment. Nat Rev Neurol 12:455\u2013464","journal-title":"Nat Rev Neurol"},{"key":"2457_CR4","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1136\/jnnp-2015-312233","volume":"87","author":"MT Minen","year":"2016","unstructured":"Minen MT, De Begasse O, Van Kroon A, Powers S, Schwedt TJ, Lipton R, Silbersweig D (2016) Migraine and its psychiatric comorbidities. J Neurol Neurosurg Psychiatry 87:741\u2013749","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2457_CR5","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1136\/jnnp.2009.192492","volume":"81","author":"DC Buse","year":"2010","unstructured":"Buse DC, Manack A, Serrano D, Turkel C, Lipton RB (2010) Sociodemographic and comorbidity profiles of chronic migraine and episodic migraine sufferers. J Neurol Neurosurg Psychiatry 81:428\u2013432","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2457_CR6","doi-asserted-by":"publisher","first-page":"1960","DOI":"10.1007\/s00415-012-6725-x","volume":"260","author":"DC Buse","year":"2013","unstructured":"Buse DC, Silberstein SD, Manack AN, Papapetropoulos S, Lipton RB (2013) Psychiatric comorbidities of episodic and chronic migraine. J Neurol 260:1960\u20131969","journal-title":"J Neurol"},{"key":"2457_CR7","doi-asserted-by":"crossref","first-page":"e067670","DOI":"10.1136\/bmj-2021-067670","volume":"379","author":"A Hovaguimian","year":"2022","unstructured":"Hovaguimian A, Roth J (2022) Management of chronic migraine. BMJ 379:e067670","journal-title":"BMJ"},{"key":"2457_CR8","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1016\/j.pain.2014.03.001","volume":"155","author":"N Boyer","year":"2014","unstructured":"Boyer N, Dallel R, Artola A, Monconduit L (2014) General trigeminospinal central sensitization and impaired descending pain inhibitory controls contribute to migraine progression. Pain 155:1196\u20131205","journal-title":"Pain"},{"key":"2457_CR9","doi-asserted-by":"crossref","first-page":"245","DOI":"10.3949\/ccjm.90a.22019","volume":"90","author":"MM Volcheck","year":"2023","unstructured":"Volcheck MM, Graham SM, Fleming KC, Mohabbat AB, Luedtke CA (2023) Central sensitization, chronic pain, and other symptoms: Better understanding, better management. Cleve Clin J Med 90:245\u2013254","journal-title":"Cleve Clin J Med"},{"key":"2457_CR10","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s12974-025-03367-w","volume":"22","author":"J Hu","year":"2025","unstructured":"Hu J, Ji W, Liu G, Su X, Zhu J, Hong Y, Xiong Y, Zhao Y, Li W, Xie W (2025) IDO1 modulates pain sensitivity and comorbid anxiety in chronic migraine through microglial activation and synaptic pruning. J Neuroinflammation 22:42","journal-title":"J Neuroinflammation"},{"key":"2457_CR11","doi-asserted-by":"publisher","first-page":"3697","DOI":"10.1007\/s12035-023-03781-2","volume":"61","author":"X Liu","year":"2024","unstructured":"Liu X, Yang W, Zhu C, Sun S, Yang B, Wu S, Wang L, Liu Z, Ge Z (2024) TLR2 Mediates Microglial Activation and Contributes to Central Sensitization in a Recurrent Nitroglycerin-induced Chronic Migraine Model. Mol Neurobiol 61:3697\u20133714","journal-title":"Mol Neurobiol"},{"key":"2457_CR12","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/S1474-4422(19)30185-1","volume":"18","author":"M Ashina","year":"2019","unstructured":"Ashina M, Hansen JM, Do TP, Melo-Carrillo A, Burstein R, Moskowitz MA (2019) Migraine and the trigeminovascular system-40 years and counting. Lancet Neurol 18:795\u2013804","journal-title":"Lancet Neurol"},{"key":"2457_CR13","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1177\/03331024221118924","volume":"42","author":"J Thuraiaiyah","year":"2022","unstructured":"Thuraiaiyah J, Erritzoe-Jervild M, Al-Khazali HM, Schytz HW, Younis S (2022) The role of cytokines in migraine: A systematic review. Cephalalgia 42:1565\u20131588","journal-title":"Cephalalgia"},{"key":"2457_CR14","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1038\/nrn.2018.2","volume":"19","author":"K Inoue","year":"2018","unstructured":"Inoue K, Tsuda M (2018) Microglia in neuropathic pain: cellular and molecular mechanisms and therapeutic potential. Nat Rev Neurosci 19:138\u2013152","journal-title":"Nat Rev Neurosci"},{"key":"2457_CR15","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1186\/s12974-021-02342-5","volume":"18","author":"Q Wen","year":"2021","unstructured":"Wen Q, Wang Y, Pan Q, Tian R, Zhang D, Qin G, Zhou J, Chen L (2021) MicroRNA-155-5p promotes neuroinflammation and central sensitization via inhibiting SIRT1 in a nitroglycerin-induced chronic migraine mouse model. J Neuroinflammation 18:287","journal-title":"J Neuroinflammation"},{"key":"2457_CR16","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1186\/s12974-018-1285-3","volume":"15","author":"T Long","year":"2018","unstructured":"Long T, He W, Pan Q, Zhang S, Zhang Y, Liu C, Liu Q, Qin G, Chen L, Zhou J (2018) Microglia P2X4 receptor contributes to central sensitization following recurrent nitroglycerin stimulation. J Neuroinflammation 15:245","journal-title":"J Neuroinflammation"},{"key":"2457_CR17","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.bbi.2014.09.004","volume":"44","author":"SS Lewis","year":"2015","unstructured":"Lewis SS, Hutchinson MR, Frick MM, Zhang Y, Maier SF, Sammakia T, Rice KC, Watkins LR (2015) Select steroid hormone glucuronide metabolites can cause toll-like receptor 4 activation and enhanced pain. Brain Behav Immun 44:128\u2013136","journal-title":"Brain Behav Immun"},{"key":"2457_CR18","doi-asserted-by":"crossref","first-page":"2069295678","DOI":"10.1177\/1744806919867842","volume":"15","author":"R Ramachandran","year":"2019","unstructured":"Ramachandran R, Wang Z, Saavedra C, DiNardo A, Corr M, Powell SB, Yaksh TL (2019) Role of Toll-like receptor 4 signaling in mast cell-mediated migraine pain pathway. Mol Pain 15:2069295678","journal-title":"Mol Pain"},{"key":"2457_CR19","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1097\/j.pain.0000000000001306","volume":"159","author":"K Bruno","year":"2018","unstructured":"Bruno K, Woller SA, Miller YI, Yaksh TL, Wallace M, Beaton G, Chakravarthy K (2018) Targeting toll-like receptor-4 (TLR4)-an emerging therapeutic target for persistent pain states. Pain 159:1908\u20131915","journal-title":"Pain"},{"key":"2457_CR20","doi-asserted-by":"crossref","first-page":"2989","DOI":"10.1093\/brain\/awad045","volume":"146","author":"P Chen","year":"2023","unstructured":"Chen P, Yen J, Liu T, Chen S, Wang S, Chen S (2023) Neuronal NLRP3 inflammasome mediates spreading depolarization-evoked trigeminovascular activation. Brain 146:2989\u20133002","journal-title":"Brain"},{"key":"2457_CR21","doi-asserted-by":"crossref","first-page":"899","DOI":"10.2147\/JPR.S116968","volume":"9","author":"YH Kwok","year":"2016","unstructured":"Kwok YH, Swift JE, Gazerani P, Rolan P (2016) A double-blind, randomized, placebo-controlled pilot trial to determine the efficacy and safety of ibudilast, a potential glial attenuator, in chronic migraine. J Pain Res 9:899\u2013907","journal-title":"J Pain Res"},{"key":"2457_CR22","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1111\/head.12655","volume":"55","author":"JL Johnson","year":"2015","unstructured":"Johnson JL, Kwok YH, Sumracki NM, Swift JE, Hutchinson MR, Johnson K, Williams DB, Tuke J, Rolan PE (2015) Glial Attenuation With Ibudilast in the Treatment of Medication Overuse Headache: A Double-Blind, Randomized, Placebo-Controlled Pilot Trial of Efficacy and Safety. Headache 55:1192\u20131208","journal-title":"Headache"},{"key":"2457_CR23","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.jaut.2019.04.020","volume":"102","author":"B Liu","year":"2019","unstructured":"Liu B, Gu Y, Pei S, Peng Y, Chen J, Pham LV, Shen H, Zhang J, Wang H (2019) Interleukin-1 receptor associated kinase (IRAK)-M -mediated type 2 microglia polarization ameliorates the severity of experimental autoimmune encephalomyelitis (EAE). J Autoimmun 102:77\u201388","journal-title":"J Autoimmun"},{"key":"2457_CR24","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1038\/s41419-023-05621-6","volume":"14","author":"Y Wang","year":"2023","unstructured":"Wang Y, Pei S, Liu Z, Ding Y, Qian T, Wen H, Hsu S, Zhou Z, Zhang J, Wang H (2023) IRAK-M suppresses the activation of microglial NLRP3 inflammasome and GSDMD-mediated pyroptosis through inhibiting IRAK1 phosphorylation during experimental autoimmune encephalomyelitis. Cell Death Dis 14:103","journal-title":"Cell Death Dis"},{"key":"2457_CR25","doi-asserted-by":"publisher","first-page":"5199","DOI":"10.1007\/s12035-023-03407-7","volume":"60","author":"X Liang","year":"2023","unstructured":"Liang X, Qian T, Xiong Y, Liang X, Ding Y, Zhu X, Li Y, Zhou J, Tan L, Li W, Xie W (2023) IRAK-M Ablation Promotes Status Epilepticus-Induced Neuroinflammation via Activating M1 Microglia and Impairing Excitatory Synaptic Function. Mol Neurobiol 60:5199\u20135213","journal-title":"Mol Neurobiol"},{"key":"2457_CR26","doi-asserted-by":"crossref","first-page":"156751","DOI":"10.1016\/j.phymed.2025.156751","volume":"142","author":"S Chang","year":"2025","unstructured":"Chang S, Li Y, Zhu H, He Z, You Y, Liu Y (2025) Buyang Huanwu Decoction stabilizes atherosclerotic vulnerable plaques by regulating intestinal flora, TLR4-NF-kappaB-NLRP3 inflammatory pathway and mitophagy. Phytomedicine 142:156751","journal-title":"Phytomedicine"},{"key":"2457_CR27","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1186\/s12951-025-03176-6","volume":"23","author":"X Chen","year":"2025","unstructured":"Chen X, Dai C, Zhang B, Zhang W, Huang Z, Jiang J, Hu S, Ma J, Feng J (2025) RGD hydrogel-loaded ADSC extracellular vesicles mitigate uranium-induced renal injury via TLR4\/NF-kappaB pathway inhibition. J Nanobiotechnol 23:114","journal-title":"J Nanobiotechnol"},{"key":"2457_CR28","doi-asserted-by":"crossref","first-page":"138376","DOI":"10.1016\/j.jhazmat.2025.138376","volume":"493","author":"S Ran","year":"2025","unstructured":"Ran S, Li W, Yang Z, Zhang J, Chen Z, Jia G, Lin Q, Zeng H, Yang Y, Zhang Z et al (2025) In vitro and in vivo evidence on the association of pregnant PM(2.5) exposure with preterm birth and potential role of placental miRNA-21 regulating TLR4\/NF-kappaB and activating NLRP3 inflammasome. J Hazard Mater 493:138376","journal-title":"J Hazard Mater"},{"key":"2457_CR29","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.immuni.2008.02.005","volume":"28","author":"JP Ting","year":"2008","unstructured":"Ting JP, Lovering RC, Alnemri ES, Bertin J, Boss JM, Davis BK, Flavell RA, Girardin SE, Godzik A, Harton JA et al (2008) The NLR gene family: a standard nomenclature. Immunity 28:285\u2013287","journal-title":"Immunity"},{"key":"2457_CR30","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1038\/nri3452","volume":"13","author":"E Latz","year":"2013","unstructured":"Latz E, Xiao TS, Stutz A (2013) Activation and regulation of the inflammasomes. Nat Rev Immunol 13:397\u2013411","journal-title":"Nat Rev Immunol"},{"key":"2457_CR31","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s10194-023-01707-w","volume":"25","author":"S Sun","year":"2024","unstructured":"Sun S, Fan Z, Liu X, Wang L, Ge Z (2024) Microglia TREM1-mediated neuroinflammation contributes to central sensitization via the NF-kappaB pathway in a chronic migraine model. J Headache Pain 25:3","journal-title":"J Headache Pain"},{"key":"2457_CR32","doi-asserted-by":"crossref","first-page":"110796","DOI":"10.1016\/j.pnpbp.2023.110796","volume":"126","author":"W Su","year":"2023","unstructured":"Su W, Li J, Zhang T, Cao Z, Hu T, Zhong S, Xu Z, Gong H, Jiang C (2023) Microglial NLRP3 inflammasome activation mediates diabetes-induced depression-like behavior via triggering neuroinflammation. Prog Neuropsychopharmacol Biol Psychiatry 126:110796","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"2457_CR33","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/s12974-019-1459-7","volume":"16","author":"W He","year":"2019","unstructured":"He W, Long T, Pan Q, Zhang S, Zhang Y, Zhang D, Qin G, Chen L, Zhou J (2019) Microglial NLRP3 inflammasome activation mediates IL-1beta release and contributes to central sensitization in a recurrent nitroglycerin-induced migraine model. J Neuroinflammation 16:78","journal-title":"J Neuroinflammation"},{"key":"2457_CR34","doi-asserted-by":"crossref","first-page":"1177171","DOI":"10.3389\/fnmol.2023.1177171","volume":"16","author":"Y Wang","year":"2023","unstructured":"Wang Y, Dong L, Zhang Y, Zhang Y, Qin G, Zhang D, Chen L, He W, Zhou J (2023) Activation of the microglial P2X7R\/NLRP3 inflammasome mediates central sensitization in a mouse model of medication overuse headache. Front Mol Neurosci 16:1177171","journal-title":"Front Mol Neurosci"},{"key":"2457_CR35","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s10194-022-01442-8","volume":"23","author":"Y Wang","year":"2022","unstructured":"Wang Y, Shan Z, Zhang L, Fan S, Zhou Y, Hu L, Wang Y, Li W, Xiao Z (2022) P2X7R\/NLRP3 signaling pathway-mediated pyroptosis and neuroinflammation contributed to cognitive impairment in a mouse model of migraine. J Headache Pain 23:75","journal-title":"J Headache Pain"},{"key":"2457_CR36","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1007\/s13760-024-02523-y","volume":"124","author":"R Ocal","year":"2024","unstructured":"Ocal R, Buldukoglu OC, Hasoglan MG, Korucuk M, Cekin Y, Ocal S (2024) Migraine and gasdermin D: a new perspective on the inflammatory basis of migraine. Acta Neurol Belg 124:981\u2013986","journal-title":"Acta Neurol Belg"},{"key":"2457_CR37","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.pain.2013.10.004","volume":"155","author":"AA Pradhan","year":"2014","unstructured":"Pradhan AA, Smith ML, McGuire B, Tarash I, Evans CJ, Charles A (2014) Characterization of a novel model of chronic migraine. Pain 155:269\u2013274","journal-title":"Pain"},{"key":"2457_CR38","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1186\/s10194-025-02203-z","volume":"26","author":"Y Xu","year":"2025","unstructured":"Xu Y, Deng Y, Wu P, Tian M, Liu C, Liu X, Liu D, Guo Y, Wang P, Xu Y et al (2025) Selective loss and transcriptional reprogramming of Nox4(+) GABAergic neurons in the trigeminal nucleus caudalis of NTG-induced chronic migraine model. J Headache Pain 26:263","journal-title":"J Headache Pain"},{"key":"2457_CR39","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.neuropharm.2017.11.036","volume":"130","author":"AJ Shepherd","year":"2018","unstructured":"Shepherd AJ, Mohapatra DP (2018) Pharmacological validation of voluntary gait and mechanical sensitivity assays associated with inflammatory and neuropathic pain in mice. Neuropharmacology 130:18\u201329","journal-title":"Neuropharmacology"},{"key":"2457_CR40","doi-asserted-by":"crossref","first-page":"38","DOI":"10.3389\/fncel.2018.00038","volume":"12","author":"AJ Shepherd","year":"2018","unstructured":"Shepherd AJ, Mickle AD, Kadunganattil S, Hu H, Mohapatra DP (2018) Parathyroid Hormone-Related Peptide Elicits Peripheral TRPV1-dependent Mechanical Hypersensitivity. Front Cell Neurosci 12:38","journal-title":"Front Cell Neurosci"},{"key":"2457_CR41","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0165-0270(94)90144-9","volume":"53","author":"SR Chaplan","year":"1994","unstructured":"Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL (1994) Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods 53:55\u201363","journal-title":"J Neurosci Methods"},{"key":"2457_CR42","doi-asserted-by":"crossref","first-page":"284","DOI":"10.3389\/fnmol.2017.00284","volume":"10","author":"JR Deuis","year":"2017","unstructured":"Deuis JR, Dvorakova LS, Vetter I (2017) Methods Used to Evaluate Pain Behaviors in Rodents. Front Mol Neurosci 10:284","journal-title":"Front Mol Neurosci"},{"key":"2457_CR43","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1186\/s10194-024-01779-2","volume":"25","author":"L Wang","year":"2024","unstructured":"Wang L, Liu X, Zhu C, Wu S, Li Z, Jing L, Zhang Z, Jing Y, Wang Y (2024) Environmental enrichment alleviates hyperalgesia by modulating central sensitization in a nitroglycerin-induced chronic migraine model of mice. J Headache Pain 25:74","journal-title":"J Headache Pain"},{"key":"2457_CR44","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1038\/s41398-025-03313-7","volume":"15","author":"X Liang","year":"2025","unstructured":"Liang X, Ding Y, Zhu X, Qiu J, Shen X, Xiong Y, Zhou J, Liang X, Xie W (2025) Suprachiasmatic nucleus dysfunction induces anxiety- and depression-like behaviors via activating the BDNF-TrkB pathway of the striatum. Transl Psychiatry 15:92","journal-title":"Transl Psychiatry"},{"key":"2457_CR45","doi-asserted-by":"crossref","first-page":"e12993","DOI":"10.1111\/jpi.12993","volume":"76","author":"X Liang","year":"2024","unstructured":"Liang X, Liang X, Zhao Y, Ding Y, Zhu X, Zhou J, Qiu J, Shen X, Xie W (2024) Dysregulation of the Suprachiasmatic Nucleus Disturbs the Circadian Rhythm and Aggravates Epileptic Seizures by Inducing Hippocampal GABAergic Dysfunction in C57BL\/6 Mice. J Pineal Res 76:e12993","journal-title":"J Pineal Res"},{"key":"2457_CR46","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.tins.2024.08.009","volume":"47","author":"J Zhang","year":"2024","unstructured":"Zhang J, Simoes R, Guo T, Cao Y (2024) Neuroimmune interactions in the development and chronification of migraine headache. Trends Neurosci 47:819\u2013833","journal-title":"Trends Neurosci"},{"key":"2457_CR47","doi-asserted-by":"crossref","first-page":"115133","DOI":"10.1016\/j.intimp.2025.115133","volume":"162","author":"H Wang","year":"2025","unstructured":"Wang H, Wen H, Yang Y, Zhong J, Zhang W, Qing G, Zhang D, Chen L (2025) CCL2 activates NLRP3 inflammasomes to regulate microglial phenotype transformation to promote central sensitisation in chronic migraine. Int Immunopharmacol 162:115133","journal-title":"Int Immunopharmacol"},{"key":"2457_CR48","doi-asserted-by":"publisher","first-page":"4334","DOI":"10.1007\/s00259-025-07282-3","volume":"52","author":"Y Chang","year":"2025","unstructured":"Chang Y, Zhang X, Xiao S, Liu J, Wang Y, Song J, Fu H, Li Y, Su H, Yi H et al (2025) Evidence for brain glial activity in chronic migraine patients: a [(11)C] PBR28 PET\/MR study. Eur J Nucl Med Mol Imaging 52:4334\u20134344","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"2457_CR49","doi-asserted-by":"crossref","first-page":"S8","DOI":"10.1212\/WNL.0b013e31819749fd","volume":"72","author":"SK Aurora","year":"2009","unstructured":"Aurora SK (2009) Spectrum of illness: understanding biological patterns and relationships in chronic migraine. Neurology 72:S8\u2013S13","journal-title":"Neurology"},{"key":"2457_CR50","doi-asserted-by":"crossref","first-page":"89","DOI":"10.3988\/jcn.2012.8.2.89","volume":"8","author":"C Bernstein","year":"2012","unstructured":"Bernstein C, Burstein R (2012) Sensitization of the trigeminovascular pathway: perspective and implications to migraine pathophysiology. J Clin Neurol 8:89\u201399","journal-title":"J Clin Neurol"},{"key":"2457_CR51","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0304-3959(00)00478-4","volume":"89","author":"R Burstein","year":"2001","unstructured":"Burstein R (2001) Deconstructing migraine headache into peripheral and central sensitization. Pain 89:107\u2013110","journal-title":"Pain"},{"key":"2457_CR52","doi-asserted-by":"crossref","first-page":"2059604794","DOI":"10.1177\/03331024251317446","volume":"45","author":"G Guzman","year":"2025","unstructured":"Guzman G, Kopruszinski CM, Barber KR, Lillo Vizin RC, Dodick DW, Navratilova E, Porreca F (2025) Chronification of migraine sensitizes to CGRP in male and female mice. Cephalalgia 45:2059604794","journal-title":"Cephalalgia"},{"key":"2457_CR53","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1016\/j.neuron.2018.11.009","volume":"100","author":"G Chen","year":"2018","unstructured":"Chen G, Zhang Y, Qadri YJ, Serhan CN, Ji R (2018) Microglia in Pain: Detrimental and Protective Roles in Pathogenesis and Resolution of Pain. Neuron 100:1292\u20131311","journal-title":"Neuron"},{"key":"2457_CR54","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1186\/s12951-022-01522-6","volume":"20","author":"T Hua","year":"2022","unstructured":"Hua T, Yang M, Song H, Kong E, Deng M, Li Y, Li J, Liu Z, Fu H, Wang Y, Yuan H (2022) Huc-MSCs-derived exosomes attenuate inflammatory pain by regulating microglia pyroptosis and autophagy via the miR-146a-5p\/TRAF6 axis. J Nanobiotechnol 20:324","journal-title":"J Nanobiotechnol"},{"key":"2457_CR55","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.bbi.2024.02.027","volume":"118","author":"T Hua","year":"2024","unstructured":"Hua T, Kong E, Zhang H, Lu J, Huang K, Ding R, Wang H, Li J, Han C, Yuan H (2024) PRMT6 deficiency or inhibition alleviates neuropathic pain by decreasing glycolysis and inflammation in microglia. Brain Behav Immun 118:101\u2013114","journal-title":"Brain Behav Immun"},{"key":"2457_CR56","doi-asserted-by":"crossref","unstructured":"Navia-Pelaez JM, Choi S, Dos Santos Aggum Capettini L, Xia Y, Gonen A, Agatisa-Boyle C, Delay L, Goncalves Dos Santos G, Catroli GF, Kim J et al (2021) Normalization of cholesterol metabolism in spinal microglia alleviates neuropathic pain. J Exp Med 218(7):e20202059","DOI":"10.1084\/jem.20202059"},{"key":"2457_CR57","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s10194-024-01739-w","volume":"25","author":"G Lu","year":"2024","unstructured":"Lu G, Xiao S, Meng F, Zhang L, Chang Y, Zhao J, Gao N, Su W, Guo X, Liu Y et al (2024) AMPK activation attenuates central sensitization in a recurrent nitroglycerin-induced chronic migraine mouse model by promoting microglial M2-type polarization. J Headache Pain 25:29","journal-title":"J Headache Pain"},{"key":"2457_CR58","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.pharmthera.2005.07.001","volume":"109","author":"K Inoue","year":"2006","unstructured":"Inoue K (2006) The function of microglia through purinergic receptors: neuropathic pain and cytokine release. Pharmacol Ther 109:210\u2013226","journal-title":"Pharmacol Ther"},{"key":"2457_CR59","doi-asserted-by":"crossref","first-page":"5856","DOI":"10.1073\/pnas.0501634102","volume":"102","author":"FY Tanga","year":"2005","unstructured":"Tanga FY, Nutile-McMenemy N, DeLeo JA (2005) The CNS role of Toll-like receptor 4 in innate neuroimmunity and painful neuropathy. Proc Natl Acad Sci U S A 102:5856\u20135861","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2457_CR60","doi-asserted-by":"publisher","first-page":"2933","DOI":"10.1038\/s41467-022-30467-5","volume":"13","author":"I Francos-Quijorna","year":"2022","unstructured":"Francos-Quijorna I, Sanchez-Petidier M, Burnside ER, Badea SR, Torres-Espin A, Marshall L, de Winter F, Verhaagen J, Moreno-Manzano V, Bradbury EJ (2022) Chondroitin sulfate proteoglycans prevent immune cell phenotypic conversion and inflammation resolution via TLR4 in rodent models of spinal cord injury. Nat Commun 13:2933","journal-title":"Nat Commun"},{"key":"2457_CR61","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.bbi.2023.05.008","volume":"111","author":"X Wang","year":"2023","unstructured":"Wang X, Lin C, Jin S, Wang Y, Peng Y, Wang X (2023) Cannabidiol alleviates neuroinflammation and attenuates neuropathic pain via targeting FKBP5. Brain Behav Immun 111:365\u2013375","journal-title":"Brain Behav Immun"},{"key":"2457_CR62","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1097\/j.pain.0000000000000959","volume":"158","author":"H Lim","year":"2017","unstructured":"Lim H, Lee H, Noh K, Lee SJ (2017) IKK\/NF-kappaB-dependent satellite glia activation induces spinal cord microglia activation and neuropathic pain after nerve injury. Pain 158:1666\u20131677","journal-title":"Pain"},{"key":"2457_CR63","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1007\/s11427-024-2789-1","volume":"68","author":"Z Han","year":"2025","unstructured":"Han Z, Fu J, Gong A, Ren W (2025) Bacterial indole-3-propionic acid inhibits macrophage IL-1beta production through targeting methionine metabolism. Sci China Life Sci 68:1118\u20131131","journal-title":"Sci China Life Sci"},{"key":"2457_CR64","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1038\/s41423-023-01089-8","volume":"20","author":"J Cao","year":"2023","unstructured":"Cao J, Ji L, Zhan Y, Shao X, Xu P, Wu B, Chen P, Cheng L, Zhuang X, Ou Y et al (2023) MST4 kinase regulates immune thrombocytopenia by phosphorylating STAT1-mediated M1 polarization of macrophages. Cell Mol Immunol 20:1413\u20131427","journal-title":"Cell Mol Immunol"},{"key":"2457_CR65","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1038\/s41419-024-07268-3","volume":"15","author":"Y Bai","year":"2024","unstructured":"Bai Y, Xing Y, Ma T, Li K, Zhang T, Wang D, Wan S, Zhang C, Sun Y, Wang M et al (2024) beta-Hydroxybutyrate suppresses M1 macrophage polarization through beta-hydroxybutyrylation of the STAT1 protein. Cell Death Dis 15:874","journal-title":"Cell Death Dis"},{"key":"2457_CR66","doi-asserted-by":"crossref","unstructured":"Li M, Wang M, Wen Y, Zhang H, Zhao G, Gao Q (2020) Signaling pathways in macrophages: molecular mechanisms and therapeutic targets. MedComm 2023; 4:e349","DOI":"10.1002\/mco2.349"},{"key":"2457_CR67","first-page":"614","volume":"5","author":"N Wang","year":"2014","unstructured":"Wang N, Liang H, Zen K (2014) Molecular mechanisms that influence the macrophage m1-m2 polarization balance. Front Immunol 5:614","journal-title":"Front Immunol"},{"key":"2457_CR68","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S0092-8674(02)00827-9","volume":"110","author":"K Kobayashi","year":"2002","unstructured":"Kobayashi K, Hernandez LD, Galan JE, Janeway CAJ, Medzhitov R, Flavell RA (2002) IRAK-M is a negative regulator of Toll-like receptor signaling. Cell 110:191\u2013202","journal-title":"Cell"},{"key":"2457_CR69","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1186\/s12866-017-1095-2","volume":"17","author":"P Shen","year":"2017","unstructured":"Shen P, Li Q, Ma J, Tian M, Hong F, Zhai X, Li J, Huang H, Shi C (2017) IRAK-M alters the polarity of macrophages to facilitate the survival of Mycobacterium tuberculosis. BMC Microbiol 17:185","journal-title":"BMC Microbiol"},{"key":"2457_CR70","doi-asserted-by":"crossref","first-page":"17023","DOI":"10.1038\/sigtrans.2017.23","volume":"2","author":"T Liu","year":"2017","unstructured":"Liu T, Zhang L, Joo D, Sun S (2017) NF-kappaB signaling in inflammation. Signal Transduct Target Ther 2:17023","journal-title":"Signal Transduct Target Ther"},{"key":"2457_CR71","doi-asserted-by":"crossref","first-page":"879021","DOI":"10.3389\/fnagi.2022.879021","volume":"14","author":"HM Blevins","year":"2022","unstructured":"Blevins HM, Xu Y, Biby S, Zhang S (2022) The NLRP3 Inflammasome Pathway: A Review of Mechanisms and Inhibitors for the Treatment of Inflammatory Diseases. Front Aging Neurosci 14:879021","journal-title":"Front Aging Neurosci"},{"key":"2457_CR72","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1186\/s12974-014-0222-3","volume":"12","author":"X Yan","year":"2015","unstructured":"Yan X, Jiang E, Weng H (2015) Activation of toll like receptor 4 attenuates GABA synthesis and postsynaptic GABA receptor activities in the spinal dorsal horn via releasing interleukin-1 beta. J Neuroinflammation 12:222","journal-title":"J Neuroinflammation"},{"key":"2457_CR73","first-page":"16","volume":"9","author":"T Liu","year":"2013","unstructured":"Liu T, Jiang C, Fujita T, Luo S, Kumamoto E (2013) Enhancement by interleukin-1beta of AMPA and NMDA receptor-mediated currents in adult rat spinal superficial dorsal horn neurons. Mol Pain 9:16","journal-title":"Mol Pain"},{"key":"2457_CR74","doi-asserted-by":"crossref","first-page":"8692","DOI":"10.1523\/JNEUROSCI.23-25-08692.2003","volume":"23","author":"B Viviani","year":"2003","unstructured":"Viviani B, Bartesaghi S, Gardoni F, Vezzani A, Behrens MM, Bartfai T, Binaglia M, Corsini E, Di Luca M, Galli CL, Marinovich M (2003) Interleukin-1beta enhances NMDA receptor-mediated intracellular calcium increase through activation of the Src family of kinases. J Neurosci 23:8692\u20138700","journal-title":"J Neurosci"},{"key":"2457_CR75","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1001\/jamapediatrics.2022.3940","volume":"176","author":"K Falla","year":"2022","unstructured":"Falla K, Kuziek J, Mahnaz SR, Noel M, Ronksley PE, Orr SL (2022) Anxiety and Depressive Symptoms and Disorders in Children and Adolescents With Migraine: A Systematic Review and Meta-analysis. JAMA Pediatr 176:1176\u20131187","journal-title":"JAMA Pediatr"},{"key":"2457_CR76","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1177\/014107689408700613","volume":"87","author":"J Devlen","year":"1994","unstructured":"Devlen J (1994) Anxiety and depression in migraine. J R Soc Med 87:338\u2013341","journal-title":"J R Soc Med"},{"key":"2457_CR77","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/s10194-019-0963-6","volume":"20","author":"D Vuralli","year":"2019","unstructured":"Vuralli D, Wattiez A, Russo AF, Bolay H (2019) Behavioral and cognitive animal models in headache research. J Headache Pain 20:11","journal-title":"J Headache Pain"},{"key":"2457_CR78","doi-asserted-by":"crossref","unstructured":"Seibenhener ML, Wooten MC (2015) Use of the Open Field Maze to measure locomotor and anxiety-like behavior in mice. J Vis Exp (96):e52434.","DOI":"10.3791\/52434-v"},{"key":"2457_CR79","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1038\/nprot.2007.44","volume":"2","author":"AA Walf","year":"2007","unstructured":"Walf AA, Frye CA (2007) The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat Protoc 2:322\u2013328","journal-title":"Nat Protoc"},{"key":"2457_CR80","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1038\/nn.4053","volume":"18","author":"RE Sorge","year":"2015","unstructured":"Sorge RE, Mapplebeck JCS, Rosen S, Beggs S, Taves S, Alexander JK, Martin LJ, Austin J, Sotocinal SG, Chen D et al (2015) Different immune cells mediate mechanical pain hypersensitivity in male and female mice. Nat Neurosci 18:1081\u20131083","journal-title":"Nat Neurosci"},{"key":"2457_CR81","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1097\/j.pain.0000000000002034","volume":"162","author":"R Rudjito","year":"2021","unstructured":"Rudjito R, Agalave NM, Farinotti AB, Lundback P, Szabo-Pardi TA, Price TJ, Harris HE, Burton MD, Svensson CI (2021) Sex- and cell-dependent contribution of peripheral high mobility group box 1 and TLR4 in arthritis-induced pain. Pain 162:459\u2013470","journal-title":"Pain"},{"key":"2457_CR82","doi-asserted-by":"crossref","first-page":"4349","DOI":"10.1523\/JNEUROSCI.1940-20.2021","volume":"41","author":"NA Huck","year":"2021","unstructured":"Huck NA, Siliezar-Doyle J, Haight ES, Ishida R, Forman TE, Wu S, Shen H, Takemura Y, Clark JD, Tawfik VL (2021) Temporal Contribution of Myeloid-Lineage TLR4 to the Transition to Chronic Pain: A Focus on Sex Differences. J Neurosci 41:4349\u20134365","journal-title":"J Neurosci"},{"key":"2457_CR83","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1001\/jama.2023.5536","volume":"329","author":"R Marcus","year":"2023","unstructured":"Marcus R (2023) Study Provides New Insight Into Female Sex Hormones and Migraines. JAMA 329:1439\u20131440","journal-title":"JAMA"}],"container-title":["The Journal of Headache and Pain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s10194-026-02457-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s10194-026-02457-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s10194-026-02457-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:08:54Z","timestamp":1792062534000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s10194-026-02457-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,17]]},"references-count":83,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["2457"],"URL":"https:\/\/doi.org\/10.1186\/s10194-026-02457-1","relation":{},"ISSN":["1129-2377"],"issn-type":[{"value":"1129-2377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,17]]},"assertion":[{"value":"3 June 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All animal experiments were conducted in accordance with protocols approved by the Institutional Animal Care and Use Committee of Southern Medical University (approval no. L202406032, Guangdong, China).","order":1,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","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":"241"}}