{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T02:07:00Z","timestamp":1755223620762,"version":"3.43.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T00:00:00Z","timestamp":1754956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Cancer-induced bone pain (CIBP) represents a formidable clinical challenge with complex mechanisms, and existing treatments remain unable to effectively control pain in many patients. This study combined bibliometric and bioinformatic approaches to delineate key research trends, principal themes and future directions in the field of bone metastasis and pain research over the past decade (2015\u20132024).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We selected 1,822 relevant documents from the Web of Science Core Collection for bibliometric analysis to identify major research characteristics, collaboration networks and emerging trends. Additionally, we employed bioinformatic methods to screen core genes associated with both bone metastasis and cancer pain, and analysed their functions and signalling pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Research output and academic influence demonstrated an upward trajectory, with the United States and China being the countries with the highest publication volumes. Research hotspots are shifting from traditional palliative treatments towards precision therapies, with stereotactic body radiotherapy, minimally invasive ablation techniques and neuropathic pain mechanisms representing major research frontiers. Bioinformatic analysis identified core hub genes such as TP53 and EGFR, and revealed significant enrichment of signalling pathways including PI3K-Akt, MAPK and TNF in the common pathological processes of bone metastasis and pain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study, for the first time combining both methodologies, revealed the field\u2019s evolution from traditional treatments towards precision interventions and mechanistic exploration. The molecular targets and signalling pathways we identified provide promising directions for developing novel therapies capable of simultaneously controlling tumour progression and alleviating pain.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2025.1619607","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T05:30:33Z","timestamp":1754976633000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Bone metastasis and pain research through the dual lens of bibliometrics and bioinformatics: knowledge structure, frontiers, and core pathway analysis (2015\u20132024)"],"prefix":"10.3389","volume":"12","author":[{"given":"Linghan","family":"Meng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingna","family":"Tao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangda","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juanxia","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Shang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongtao","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haixiao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanju","family":"Bao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baojin","family":"Hua","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1152\/physrev.00012.2019","article-title":"Bone metastasis: mechanisms, therapies, and biomarkers","volume":"101","author":"Cl\u00e9zardin","year":"2021","journal-title":"Physiol Rev"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"115783","DOI":"10.1016\/j.bone.2020.115783","article-title":"Epidemiology of bone metastases","volume":"158","author":"Ryan","year":"2022","journal-title":"Bone"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.canlet.2022.01.015","article-title":"Tumor microenvironment mechanisms and bone metastatic disease progression of prostate cancer","volume":"530","author":"Kang","year":"2022","journal-title":"Cancer Lett"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1007\/s00774-022-01382-y","article-title":"Management of cancer pain due to bone metastasis","volume":"41","author":"Takei","year":"2023","journal-title":"J Bone Miner Metab"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1156618","DOI":"10.3389\/fonc.2023.1156618","article-title":"Management of pain in patients with bone metastases","volume":"13","author":"Jing","year":"2023","journal-title":"Front Oncol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"109641","DOI":"10.1016\/j.neuropharm.2023.109641","article-title":"Understanding the initiation, delivery and processing of bone cancer pain from the peripheral to the central nervous system","volume":"237","author":"Yang","year":"2023","journal-title":"Neuropharmacology"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1007\/s12264-023-01126-6","article-title":"Peripheral mechanism of cancer-induced bone pain","volume":"40","author":"Yang","year":"2024","journal-title":"Neurosci Bull"},{"key":"ref8","doi-asserted-by":"crossref","DOI":"10.5772\/intechopen.95910","article-title":"Bone cancer pain, mechanism and treatment","volume-title":"Recent advances in bone Tumours and osteoarthritis","author":"Sliepen","year":"2021"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"315","DOI":"10.2147\/JPR.S498466","article-title":"Mechanisms of cancer-induced bone pain","volume":"18","author":"Wang","year":"2025","journal-title":"J Pain Res"},{"key":"ref10","doi-asserted-by":"crossref","DOI":"10.5772\/intechopen.85856","article-title":"Bibliometric method for mapping the state-of-the-art and identifying research gaps and trends in literature: An essential instrument to support the development of scientific projects","volume-title":"Scientometrics Recent Advances","author":"Oliveira","year":"2019"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"223","DOI":"10.2147\/JMDH.S502351","article-title":"Large language models in healthcare: a bibliometric analysis and examination of research trends","volume":"18","author":"Gencer","year":"2025","journal-title":"J Multidiscip Healthc"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"6047","DOI":"10.3390\/ijms20236047","article-title":"Bone pain in cancer patients: mechanisms and current treatment","volume":"20","author":"Zaj\u0105czkowska","year":"2019","journal-title":"Int J Mol Sci"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/j.clon.2011.03.003","article-title":"Mechanisms of cancer-induced bone pain","volume":"23","author":"Middlemiss","year":"2011","journal-title":"Clin Oncol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1158\/2159-8290.CD-13-0136","article-title":"Contribution of p 53 to metastasis","volume":"4","author":"Powell","year":"2014","journal-title":"Cancer Discov"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.trecan.2019.11.004","article-title":"Mutant p 53 on the path to metastasis","volume":"6","author":"Tang","year":"2020","journal-title":"Trends Cancer"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"184","DOI":"10.31083\/j.fbl2905184","article-title":"From tumor to bone: growth factor receptors as key players in cancer metastasis","volume":"29","author":"Mohammad","year":"2024","journal-title":"Front Biosci (Landmark Ed)"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1016\/j.semcdb.2010.08.009","article-title":"EGFR signaling in breast cancer: bad to the bone","volume":"21","author":"Foley","year":"2010","journal-title":"Semin Cell Dev Biol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1558","DOI":"10.3390\/ph16111558","article-title":"Repurposing EGFR inhibitors for oral cancer pain and opioid tolerance","volume":"16","author":"Santi","year":"2023","journal-title":"Pharm (basel Switz)"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"642820","DOI":"10.3389\/fphar.2021.642820","article-title":"Modulation of pathological pain by epidermal growth factor receptor","volume":"12","author":"Borges","year":"2021","journal-title":"Front Pharmacol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1016\/j.ejca.2010.02.026","article-title":"Interleukin-6 in bone metastasis and cancer progression","volume":"46","author":"Ara","year":"2010","journal-title":"Eur J Cancer"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1023177","DOI":"10.3389\/fonc.2022.1023177","article-title":"The role of IL-6\/JAK2\/STAT3 signaling pathway in cancers","volume":"12","author":"Huang","year":"2022","journal-title":"Front Oncol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1744806919830240","DOI":"10.1177\/1744806919830240","article-title":"Neuroinflammation and central PI3K\/akt\/mTOR signal pathway contribute to bone cancer pain","volume":"15","author":"Zhang","year":"2019","journal-title":"Mol Pain"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1186\/s12974-016-0607-6","article-title":"Interleukin-6: an emerging regulator of pathological pain","volume":"13","author":"Zhou","year":"2016","journal-title":"J Neuroinflammation"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"280","DOI":"10.3390\/ijms20020280","article-title":"Bone metastasis pain, from the bench to the bedside","volume":"20","author":"Aielli","year":"2019","journal-title":"Int J Mol Sci"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1481","DOI":"10.3390\/ijms23031481","article-title":"Role of the interaction of tumor necrosis factor-\u03b1 and tumor necrosis factor receptors 1 and 2 in bone-related cells","volume":"23","author":"Kitaura","year":"2022","journal-title":"Int J Mol Sci"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"4239","DOI":"10.2147\/DDDT.S87568","article-title":"Advances in cancer pain from bone metastasis","volume":"9","author":"Zhu","year":"2015","journal-title":"Drug Des Devel Ther"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"753656","DOI":"10.1155\/2013\/753656","article-title":"Microglia and spinal cord synaptic plasticity in persistent pain","volume":"2013","author":"Taves","year":"2013","journal-title":"Neural Plast"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"2279","DOI":"10.1016\/s0149-2918(03)80219-9","article-title":"Targeted etanercept for treatment-refractory pain due to bone metastasis: two case reports","volume":"25","author":"Tobinick","year":"2003","journal-title":"Clin Ther"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1055\/a-1177-5073","article-title":"IL-17 regulates expression of cytokines in human osteoblasts rather than bone-specific genes","volume":"30","author":"Drynda","year":"2021","journal-title":"Osteologie"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"5249","DOI":"10.1016\/j.apsb.2024.09.016","article-title":"Spinal astrocyte-derived interleukin-17A promotes pain hypersensitivity in bone cancer mice","volume":"14","author":"Liu","year":"2024","journal-title":"Acta Pharm Sin B"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"3113","DOI":"10.7150\/ijbs.89942","article-title":"The PI3K\/akt pathway and glucose metabolism: a dangerous liaison in cancer","volume":"20","author":"Fontana","year":"2024","journal-title":"Int J Biol Sci"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"4261","DOI":"10.1523\/JNEUROSCI.5392-07.2008","article-title":"Phosphatidylinositol 3-kinase is a key mediator of central sensitization in painful inflammatory conditions","volume":"28","author":"Pezet","year":"2008","journal-title":"J Neurosci"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/1744-8069-7-48","article-title":"Cancer-induced bone pain sequentially activates the ERK\/MAPK pathway in different cell types in the rat spinal cord","volume":"7","author":"Wang","year":"2011","journal-title":"Mol Pain"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"293","DOI":"10.2174\/1381612826666201102103520","article-title":"Pain biomarkers in cancer: an overview","volume":"27","author":"Calapai","year":"2021","journal-title":"Curr Pharm Des"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1111\/j.1464-5491.2011.03500.x","article-title":"Validation of DN4 as a screening tool for neuropathic pain in painful diabetic polyneuropathy","volume":"29","author":"Spallone","year":"2012","journal-title":"Diabet Med J Br Diabet Assoc"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"253","DOI":"10.3344\/kjp.22392","article-title":"Neuropathic pain feature in cancer-induced bone pain: does it matter? A prospective observational study","volume":"36","author":"Zinboonyahgoon","year":"2023","journal-title":"Korean J Pain"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/s12885-021-07828-2","article-title":"Efficacy of extracranial stereotactic body radiation therapy (SBRT) added to standard treatment in patients with solid tumors (breast, prostate and non-small cell lung cancer) with up to 3 bone-only metastases: study protocol for a randomised phase III trial (STEREO-OS)","volume":"21","author":"Thureau","year":"2021","journal-title":"BMC Cancer"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1093\/neuros\/nyz213","article-title":"Strategies to mitigate toxicities from stereotactic body radiation therapy for spine metastases","volume":"85","author":"Schaub","year":"2019","journal-title":"Neurosurgery"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1619607\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T05:30:34Z","timestamp":1754976634000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1619607\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,12]]},"references-count":38,"alternative-id":["10.3389\/fmed.2025.1619607"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2025.1619607","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,12]]},"article-number":"1619607"}}