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However, the pathological mechanism and therapeutic approaches are limited. Here, we demonstrated that Na\n            <jats:sup>+<\/jats:sup>\n            \/K\n            <jats:sup>+<\/jats:sup>\n            -ATPase \u03b11 (NKA\u03b11) is a critical regulator of nociception through interaction with purinergic P2X3 receptor (P2X3R) in the dorsal root ganglion (DRG). Conditional knockout of NKA\u03b11 in transient receptor potential vanilloid 1-positive (TRPV1\n            <jats:sup>+<\/jats:sup>\n            ) neurons led to an increase in P2X3R-dependent Ca\n            <jats:sup>2+<\/jats:sup>\n            influx and neuronal hyperexcitability and also promoted pain hypersensitivity in BCP model mice. In addition, NKA\u03b11 knockout in TRPV1\n            <jats:sup>+<\/jats:sup>\n            neurons further enhanced C-C motif chemokine ligand 5 release, thereby exacerbating spinal glial cell activation and pain hypersensitivity in BCP mice. DR5-12D, a monoclonal antibody to stabilize the expression of NKA\u03b11, markedly inhibited the hyperexcitability of DRG nociceptors and ameliorated pain hypersensitivity in BCP mice. Overall, NKA\u03b11 modulates P2X3R-dependent Ca\n            <jats:sup>2+<\/jats:sup>\n            influx and the excitability of DRG nociceptors, thereby providing valuable theoretical guidance for the treatment of BCP.\n          <\/jats:p>","DOI":"10.34133\/research.0932","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T07:32:57Z","timestamp":1758267177000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":3,"title":["Na\n            <sup>+<\/sup>\n            \/K\n            <sup>+<\/sup>\n            -ATPase Modulates Purinergic P2X3 Receptor Function to Drive Bone Cancer Pain"],"prefix":"10.34133","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0085-5765","authenticated-orcid":true,"given":"Songqiang","family":"Huang","sequence":"first","affiliation":[{"name":"Affiliated Hospital of Hunan University, School of Biomedical Sciences, \rHunan University, Changsha 410082, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Peng","sequence":"additional","affiliation":[{"name":"School of Medicine, \rSouthern University of Science and Technology, Shenzhen 518055, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanting","family":"Dong","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Hunan University, School of Biomedical Sciences, \rHunan University, Changsha 410082, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiapeng","family":"He","sequence":"additional","affiliation":[{"name":"School of Medicine, \rSouthern University of Science and Technology, Shenzhen 518055, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanbin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and Diseases, SUSTech Homeostatic Medicine Institute, School of Medicine, \rSouthern University of Science and Technology, Shenzhen 518055, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8000-3356","authenticated-orcid":true,"given":"Jin-Song","family":"Bian","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and Diseases, SUSTech Homeostatic Medicine Institute, School of Medicine, \rSouthern University of Science and Technology, Shenzhen 518055, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","published-online":{"date-parts":[[2025,10,20]]},"reference":[{"issue":"3","key":"e_1_3_4_2_2","first-page":"182","article-title":"Optimal pain management for patients with cancer in the modern era","volume":"68","author":"Scarborough BM","year":"2018","unstructured":"Scarborough BM, Smith CB. 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