{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:38:37Z","timestamp":1792096717914,"version":"4.4.0"},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"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":["82271291"],"award-info":[{"award-number":["82271291"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071556"],"award-info":[{"award-number":["82071556"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82001198"],"award-info":[{"award-number":["82001198"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101310"],"award-info":[{"award-number":["82101310"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2020YFC2005303"],"award-info":[{"award-number":["2020YFC2005303"]}],"id":[{"id":"10.13039\/501100012166","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":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Advanced cancer patients still suffer from devastating bone pain, with less efficacious treatments. The spinal microglia activation and neuroinflammation are the pivotal pathological processes of cancer\u2010induced bone pain (CIBP). This study aims to explore whether c\/EBP\u03b2 negatively regulates CD200R1 to induce microglia\u2010medicated neuroinflammation in the spinal cord of CIBP mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The CIBP mice model was constructed by intrafemoral injection of Lewis lung cancer cells to investigate the role of CD200\/CD200R1 signaling and their upstream molecule CCAAT\/enhancer binding protein \u03b2 (c\/EBP\u03b2) in CIBP. Mechanical allodynia and thermal hyperalgesia were evaluated by von Frey filaments and hot plate, respectively. Adeno\u2010associated viruses were constructed to regulate the expression of CD200R1 and c\/EBP\u03b2. The protein level was assessed by western blotting, and microglia activation was detected by immunofluorescence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our results showed that CD200\/CD200R1 signaling was inhibited in the spinal cord of CIBP mice. Intrathecal injection of CD200R1 agonist CD200Fc effectively reversed the nociceptive behaviors in CIBP mice. Overexpression of CD200R1 could also effectively ameliorate the pain behaviors and spinal neuroinflammation in CIBP mice. Transcription factor c\/EBP\u03b2 was upregulated in the spinal cord of CIBP mice. Knockdown of c\/EBP\u03b2 effectively inhibited the microglia\u2010mediated neuroinflammation by restoring CD200R1 protein levels, alleviating pain behavior in CIBP mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>c\/EBP\u03b2\u2010mediated suppression of the CD200\/CD200R1 signaling pathway represents one potential mechanism in promoting microglial activation and neuroinflammation in the spinal cord of CIBP mice, which provides a potential therapeutic target for CIBP management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70824","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T11:48:45Z","timestamp":1773143325000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["C\/\n                    <scp>EBP\u03b2<\/scp>\n                    Contributes to Cancer\u2010Induced Bone Pain by Inhibiting\n                    <scp>CD200<\/scp>\n                    \/\n                    <scp>CD200R1<\/scp>\n                    in the Spinal Cord"],"prefix":"10.1002","volume":"32","author":[{"given":"Dan\u2010Yang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"},{"name":"Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health  Wuhan China"},{"name":"Wuhan Clinical Research Center for Geriatric Anesthesia  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"},{"name":"Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health  Wuhan China"},{"name":"Wuhan Clinical Research Center for Geriatric Anesthesia  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8878-8485","authenticated-orcid":false,"given":"Dai\u2010Qiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"},{"name":"Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health  Wuhan China"},{"name":"Wuhan Clinical Research Center for Geriatric Anesthesia  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long\u2010Qing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"},{"name":"Hubei Key Laboratory of Geriatric 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