{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:20:12Z","timestamp":1787163612281,"version":"build-2736575974"},"reference-count":60,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Neuropathic pain (NP) lacks clear biomarkers and effective treatment methods. We aimed to identify important genes and microRNA (miRNA)\u2013messenger RNA (mRNA) regulatory network in NP to elucidate the underlying mechanism of NP using bioinformatics analysis combined with an animal model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Two NP\u2010related gene expression datasets were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between NP and controls were identified using the limma package. Protein\u2013protein interaction (PPI) and miRNA\u2013mRNA\u2010disease networks were constructed to investigate the interactions among genes and miRNAs. Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed to investigate the biological functions of DEGs in NP. Additionally, to further confirm the expression and the functions of hub genes, a chronic constriction injury (CCI) NP rat model was established, and\n                      <jats:italic>C1qb<\/jats:italic>\n                      knockdown treatment was performed by transfection of sh\u2010C1qb.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 108 common DEGs (94 upregulated and 14 downregulated) were identified related to the pathogenesis of NP. Five hub genes (\n                      <jats:italic>Ptprc<\/jats:italic>\n                      ,\n                      <jats:italic>C1qb<\/jats:italic>\n                      ,\n                      <jats:italic>Aif1<\/jats:italic>\n                      ,\n                      <jats:italic>Fcgr2b<\/jats:italic>\n                      , and\n                      <jats:italic>Ccl2<\/jats:italic>\n                      ) were selected in the PPI network. KEGG analyses unveiled that the five hub genes were primarily involved in immune regulation and neuroinflammation especially NF\u2010\u03baB signaling pathway. miRNA\u2013mRNA\u2010disease network analysis revealed 160 miRNAs associated with the five hub genes, and 25 miRNAs (including miR\u2010124\u20103p, miR\u2010128\u20103p, and miR\u2010369\u20103p) were regulated to\n                      <jats:italic>Ptprc<\/jats:italic>\n                      ,\n                      <jats:italic>C1qb<\/jats:italic>\n                      ,\n                      <jats:italic>Fcgr2b<\/jats:italic>\n                      , and\n                      <jats:italic>Ccl2<\/jats:italic>\n                      in NP. Moreover, the expressions of Aif1, Ptprc, C1qb, Fcgr2b, and Ccl2 were increased in blood, spinal cord, dorsal root ganglia, and prefrontal cortex in NP rats compared to sham rats.\n                      <jats:italic>C1qb<\/jats:italic>\n                      knockdown alleviated the rat NP and inhibited the NF\u2010\u03baB signaling pathway.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Four hub genes (\n                      <jats:italic>Ptprc<\/jats:italic>\n                      ,\n                      <jats:italic>C1qb<\/jats:italic>\n                      ,\n                      <jats:italic>Fcgr2b<\/jats:italic>\n                      , and\n                      <jats:italic>Ccl2<\/jats:italic>\n                      ) may be potential biomarkers in NP pathogenesis, offering insights into its molecular mechanisms and suggesting therapeutic targets.\n                      <jats:italic>C1qb<\/jats:italic>\n                      knockdown is demonstrated to alleviate the NP progression through the NF\u2010\u03baB signaling pathway.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.70812","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T07:02:56Z","timestamp":1759906976000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Unraveling the Disease Mechanisms of Neuropathic Pain Through Constructing miRNA\u2013mRNA Networks Based on a Rat Model"],"prefix":"10.1002","volume":"15","author":[{"given":"Lingqi","family":"Yao","sequence":"first","affiliation":[{"name":"Department of Anesthesiology The First People's Hospital of Xiaoshan District  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3268-0546","authenticated-orcid":false,"given":"Ming","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology The First People's Hospital of Xiaoshan District  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,8]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"825","article-title":"The Diagnosis and Treatment of Neuropathic Pain","volume":"121","author":"Ahmadi R.","year":"2024","journal-title":"Dtsch Arztebl Int"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw345"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-3-15"},{"key":"e_1_2_10_5_1","volume-title":"StatPearls","author":"Ben Aziz M.","year":"2023"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurol.2018.09.016"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20122904"},{"key":"e_1_2_10_8_1","first-page":"217","article-title":"Protocatechuic Acid as an Inhibitor of the JNK\/CXCL1\/CXCR2 Pathway Relieves Neuropathic Pain in CCI Rats","volume":"22","author":"Chang H. 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