{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T05:15:04Z","timestamp":1773033304054,"version":"3.50.1"},"reference-count":55,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82001169"],"award-info":[{"award-number":["82001169"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Recent evidence has shown that bone marrow mesenchymal stem cells (BMSCs) have multiple biological applications and play an important role in improving cognitive dysfunction. However, it is still unclear whether BMSCs play a role in cognitive impairment induced by chronic pain. This study aimed to evaluate the therapeutic effect of BMSCs on neuropathic pain\u2010induced cognitive dysfunction and explore its potential mechanisms. A mouse chronic constriction injury (CCI) model was established, and the new object recognition task and fear conditioning were used to detect cognitive function; the expression of CXCL12\/CXCR4 in blood and hippocampus was detected. After intravenous injection of BMSCs, changes in cognitive function and expression of the CXCL12\/CXCR4 pathway, dentate gyrus neurogenesis, and excitability of hippocampal neurons were detected. In addition, induction of cognitive impairment in normal mice by CXCL12 recombinant protein was used to clarify whether the CXCL12\/CXCR4 pathway mediates the cognitive function improvement effect of BMSCs. Our results found CCI mice showed significant cognitive impairment 21\u2009days after surgery, with significantly increased expression of CXCL12\/CXCR4 in blood and hippocampus. Intravenous injection of BMSCs significantly improved cognitive function, inhibited expression of CXCL12\/CXCR4 in blood and hippocampus, promoted neurogenesis in dentate gyrus of CCI mice, and increased expression of BDNF and c\u2010Fos in the hippocampus. In addition, BMSCs alleviate cognitive impairment induced by intravenous injection of CXCL12 recombinant protein in mice. In summary, BMSCs improve chronic neuropathic pain\u2010induced cognitive dysfunction through peripheral blood CXCL12\/CXCR4, and BMSCs may develop into therapeutic targets for chronic pain induced cognitive impairment.<\/jats:p>","DOI":"10.1002\/jnr.70111","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T10:42:47Z","timestamp":1769596967000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bone Marrow Mesenchymal Stem Cells Improve Cognitive Impairment Induced by Neuropathic Pain Through Blood\n                    <scp>CXCL12<\/scp>\n                    \/\n                    <scp>CXCR4<\/scp>\n                    Axis in Male Mice"],"prefix":"10.1002","volume":"104","author":[{"given":"Kai","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Pain Medicine The Affiliated Hospital of Xuzhou Medical University  Xuzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Le","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Clinic Xuzhou Central Hospital  Xuzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Xuzhou Medical University  Xuzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Clinic Xuzhou Central Hospital  Xuzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0529-9949","authenticated-orcid":false,"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Clinic Xuzhou Central Hospital  Xuzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/papr.13202"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23324"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202002944"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-023-08277-9"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2024.05.012"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-019-2014-8"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1101\/lm.1650110"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3516"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI80883"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/15353702231157922"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-021-00969-3"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-022-01729-7"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20112698"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00393-7"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2025.123479"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abl8054"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.272620"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11223603"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.49717"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10561-022-10066-w"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-019-0623-x"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurom.2021.11.001"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-024-04073-z"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2024.110309"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.40241"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2013.155"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-024-01917-w"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40001-024-02207-6"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13128"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.44364"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/pm\/pnz017"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2013.04.008"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-017-0697-9"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2022-068011"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2021.02.009"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2025.111326"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.4142\/jvs.2021.22.e74"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-020-00199-x"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.2174\/1574888X14666190912162504"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389201021666200907121530"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbih.2024.100932"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-11-75"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43440-021-00323-2"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1640-z"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2019.07.035"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.2741\/4860"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbspin.2021.105222"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00333"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2022.10.001"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2020.02.013"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-1731-x"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23052550"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-025-03238-9"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1460286"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-015-0468-4"}],"container-title":["Journal of Neuroscience Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jnr.70111","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jnr.70111","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jnr.70111","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T04:26:12Z","timestamp":1773030372000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jnr.70111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,28]]},"references-count":55,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/jnr.70111"],"URL":"https:\/\/doi.org\/10.1002\/jnr.70111","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/JNR.70111\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70111\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70111\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70111\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70111\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70111\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70111\/v2\/decision1","asserted-by":"object"}]},"ISSN":["0360-4012","1097-4547"],"issn-type":[{"value":"0360-4012","type":"print"},{"value":"1097-4547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,28]]},"assertion":[{"value":"2025-04-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70111"}}