{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T07:10:07Z","timestamp":1756537807139,"version":"3.44.0"},"reference-count":65,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82360232","81960217"],"award-info":[{"award-number":["82360232","81960217"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004001","name":"Guizhou Provincial Science and Technology Department","doi-asserted-by":"publisher","award":["ZD[2025]055"],"award-info":[{"award-number":["ZD[2025]055"]}],"id":[{"id":"10.13039\/501100004001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Neonatal repetitive noxious stimuli (RNS), to mimic early\u2010life repetitive pain exposure, induce persistent hyperalgesia, anxiety\u2010like behaviors and postoperative pain sensitization that endure into adulthood. These long\u2010term neurobehavioral abnormalities are associated with impaired cognitive, emotional, and psychosocial functions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>We established a neonatal RNS rat model through repetitive needle pricks to all four limbs of neonatal rats and investigated the effects of hippocampal PRG\u20101 and synaptic remodeling at different stages in RNS rat.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our study demonstrates that hippocampal PRG\u20101 dynamically modulates RNS\u2010induced hyperalgesia and anxiety through stage\u2010specific regulation of AMPAR GluR1\/GluR2 and NMDAR GluN2A\/GluN2B trafficking, which leads to synaptic remodeling via altered dendritic synaptic morphology and synaptic transmission efficacy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings suggest that PRG\u20101 relieves RNS\u2010induced persistent hyperalgesia, anxiety, and pain\u2010perception memory via synapse remodeling at different stages. Targeting PRG\u20101\u2010mediated synaptic remodeling may provide a novel neuroprotective strategy for preventing chronic pain comorbidities with anxiety disorders following early\u2010life pain exposure.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70560","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T09:30:50Z","timestamp":1755509450000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>PRG<\/scp>\u20101 Relieves Neonatal Stimuli\u2010Induced Hyperalgesia and Anxiety via Stage\u2010Specific Synapse Remodeling"],"prefix":"10.1111","volume":"31","author":[{"given":"Wenyu","family":"Zhang","sequence":"first","affiliation":[{"name":"Guizhou Key Laboratory of Brain Science\/Key Laboratory of Anesthesia and Organ Protection of Ministry of Education (in Cultivation) Zunyi Medical University  Zunyi China"},{"name":"Department of Anesthesiology Dejiang People's Hospital  Tongren China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Guizhou Key Laboratory of Brain Science\/Key Laboratory of Anesthesia and Organ Protection of Ministry of Education (in Cultivation) Zunyi Medical University  Zunyi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangda","family":"Liang","sequence":"additional","affiliation":[{"name":"Guizhou Key Laboratory of Brain Science\/Key Laboratory of Anesthesia and Organ Protection of Ministry of Education (in Cultivation) Zunyi Medical University  Zunyi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingmei","family":"Li","sequence":"additional","affiliation":[{"name":"Guizhou Key Laboratory of Brain Science\/Key Laboratory of Anesthesia and Organ Protection of Ministry of Education (in Cultivation) Zunyi Medical University  Zunyi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhouyi","family":"Song","sequence":"additional","affiliation":[{"name":"Guizhou Key Laboratory of Brain Science\/Key Laboratory of Anesthesia and Organ Protection of Ministry of Education (in Cultivation) Zunyi Medical University  Zunyi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Song","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Pain Medicine The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital)  Dongguan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi","family":"Xiao","sequence":"additional","affiliation":[{"name":"Guizhou Key Laboratory of Brain Science\/Key Laboratory of Anesthesia and Organ Protection of Ministry of Education (in Cultivation) Zunyi Medical University  Zunyi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingfeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Guizhou Key Laboratory of Brain Science\/Key Laboratory of Anesthesia and Organ Protection of Ministry of Education (in Cultivation) Zunyi Medical University  Zunyi China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/jpepsy\/jsx140"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2022.07.010"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/Dbp.0000000000000898"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaac.2020.09.020"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.14859"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201022960\u20100"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clp.2013.10.002"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2016.05.001"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr288"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bja.2017.11.111"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.06356"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1052"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2012.08.010"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2016.06.019"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.06.050"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.59032"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104989"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010022\u201005483\u20106"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000002149"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2023.102404"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41390\u2010019\u20100420\u2010x"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.22047"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1213\/ane.0000000000003563"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.2147\/jpr.S238458"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.add2519"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2017.12.013"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109396"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2024.06.028"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000000961"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clp.2019.08.005"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210\u2010021\u201002086\u20102"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.siny.2019.04.005"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.00722"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0157240"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408398.2020.1823813"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/obr.12357"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhad051"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2008.11.003"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhw370"},{"key":"e_1_2_10_41_1","unstructured":"T.Oliver M.Muthuraman H.Johann\u2010Philipp et\u00a0al. \u201cAltered Cortical Synaptic Lipid Signaling Leads to Intermediate Phenotypes of Mental Disorders \u201d(2024) https:\/\/doi.org\/10.1038\/s41380\u2010024\u201002598\u20102."},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380\u2010018\u20100053\u20101"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201505677"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23269"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460\u20109568.2006.05091.x"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.08.035"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhw066"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255\u2010022\u201000589\u20107"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1523\/Jneurosci.1786\u201018.2019"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr288"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1097\/Aln.0000000000000658"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2010.02.008"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24010708"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304\u20103959(83)90201\u20104"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.38088"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0031\u20109384(98)00338\u20102"},{"volume-title":"The Rat Brain in Stereotaxic Coordinates","year":"2007","author":"Paxinos G.","key":"e_1_2_10_57_1"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2018.00420"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1177\/1744806918803039"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(88)90026-7"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.22038\/Ijbms.2021.57965.12904"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1590\/s0100\u2010879x2004000300017"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3102"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00682"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature25752"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12871\u2010024\u201002813\u20101"}],"container-title":["CNS Neuroscience &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cns.70560","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T06:41:58Z","timestamp":1756536118000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cns.70560"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":65,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1111\/cns.70560"],"URL":"https:\/\/doi.org\/10.1111\/cns.70560","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"type":"print","value":"1755-5930"},{"type":"electronic","value":"1755-5949"}],"subject":[],"published":{"date-parts":[[2025,8]]},"assertion":[{"value":"2025-03-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70560"}}