{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T13:38:02Z","timestamp":1791639482636,"version":"4.3.4"},"reference-count":55,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T00:00:00Z","timestamp":1744934400000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"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":["82172843"],"award-info":[{"award-number":["82172843"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2021A1515220117"],"award-info":[{"award-number":["2021A1515220117"]}],"id":[{"id":"10.13039\/501100021171","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":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Cancer\u2010induced bone pain (CIBP) is a chronic and refractory pain condition characterized by neuronal hyperexcitability, calcium dysregulation, and neuroinflammation. Voltage\u2010gated sodium channels (VGSCs) and sodium\/calcium exchangers (NCXs) are crucial in regulating sensory neuron sodium\u2013calcium homeostasis, influencing nociceptive signaling and neuroinflammatory responses. This study focused on exploring how Nav1.7 from the VGSC family and NCX1 from the NCX family influence nociceptive signaling and neuroinflammation in CIBP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>CIBP was induced in mice. Nav1.7 and NCX1 expression and colocalization in DRG neurons were analyzed by qPCR, western blotting, and immunofluorescence. Calcium overload and neuronal excitability were assessed using calcium imaging and electrophysiological recordings. Neuroinflammation markers were detected by qPCR and western blotting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among the VGSC and NCX subtypes, Nav1.7 and NCX1 were notably upregulated and colocalized in the DRG neurons of CIBP mice. Combined inhibition of these channels demonstrated a synergistic analgesic effect and markedly reduced neuronal calcium overload and hyperexcitability. Furthermore, the combined inhibition substantially alleviated neuroinflammation by inhibiting the p38 MAPK\/NF\u2010\u03baB pathway and lowering proinflammatory cytokine levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The combined inhibition of Nav1.7 and NCX1 enhances analgesic effects and reduces neuroinflammation, presenting a potential therapeutic approach for CIBP and other cancer\u2010associated pain disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70389","type":"journal-article","created":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T12:44:26Z","timestamp":1744980266000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Synergistic Inhibition of Nav1.7 and\n                    <scp>NCX<\/scp>\n                    1: A Novel Strategy for Treating Cancer\u2010Induced Bone Pain by Modulating Pain Sensitization and Neuronal Inflammation"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9070-5940","authenticated-orcid":false,"given":"Yan","family":"Feng","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer Sun Yat\u2010Sen University Cancer Center  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer Sun Yat\u2010Sen University Cancer Center  Guangzhou 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