{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T18:32:43Z","timestamp":1792607563748,"version":"4.5.0"},"reference-count":162,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Cancer pain affects 55\u201395% of patients with advanced malignancy, representing a complex syndrome involving nociceptive, neuropathic and nociplastic mechanisms. Despite therapeutic advances, two-thirds of patients with metastatic cancer experience inadequate pain control. This scoping review synthesizes recent advances in cancer pain pathophysiology and management, focusing on molecular and cellular mechanisms, emerging pharmacological, interventional and technological therapies and key evidence gaps to inform future precision-based pain management strategies. Methods: Following PRISMA-ScR methodology, we searched PubMed, Embase, Scopus, and Web of Science for studies published between January 2022 and September 2025. After screening 3412 records, 278 studies were included and analyzed across different domains: biological mechanisms, pharmacological management, interventional and neuromodulatory approaches, radiotherapy developments, and digital health innovations. Results: Recent mechanistic research reveals cancer pain arises from tumor\u2013neuron\u2013immune crosstalk, with malignant cells secreting neurotrophic factors that promote axonal sprouting and nociceptor sensitization. Genetic polymorphisms and epigenetic modifications contribute to inter-individual pain variability. Management strategies are evolving toward multimodal precision medicine: NSAIDs and opioids remain foundational, complemented by adjuvant agents and interventional procedures including nerve blocks, intrathecal delivery, and neuromodulation (spinal cord and dorsal root ganglion stimulation). Stereotactic body radiotherapy demonstrates superior analgesic durability versus conventional approaches. Digital health innovations, such as mobile applications, remote monitoring, wearables, and AI-enabled predictive models, enable continuous assessment and personalized treatment optimization. Conclusions: Cancer pain management is transitioning toward mechanism-based precision medicine integrating biological insights, advanced interventional techniques, and digital technologies. However, implementation challenges persist, including limited randomized trials for interventional approaches, the incomplete external validation of AI tools, and digital health equity concerns. Future research must prioritize prospective controlled studies and equitable integration into routine care.<\/jats:p>","DOI":"10.3390\/cancers18020259","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T15:12:04Z","timestamp":1768403524000},"page":"259","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Advances in the Pathophysiology and Management of Cancer Pain: A Scoping Review"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3822-2923","authenticated-orcid":false,"given":"Giustino","family":"Varrassi","sequence":"first","affiliation":[{"name":"Fondazione Paolo Procacci, 00193 Roma, Italy"},{"name":"College of Medicine, University of Baghdad, Baghdad 10071, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1219-9315","authenticated-orcid":false,"given":"Antonella","family":"Paladini","sequence":"additional","affiliation":[{"name":"Department of Medicina Clinica, Sanit\u00e0 Pubblica, Scienze della Vita e dell\u2019Ambiente (MESVA), University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y Van","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Binh Dan Hospital, Ho Chi Minh City 70000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3797-2337","authenticated-orcid":false,"given":"Van Phong","family":"Pham","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Binh Dan Hospital, Ho Chi Minh City 70000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ameen A.","family":"Al Alwany","sequence":"additional","affiliation":[{"name":"College of Medicine, University of Baghdad, Baghdad 10071, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9953-5635","authenticated-orcid":false,"given":"Giacomo","family":"Far\u00ec","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine (Di.Me.S.), University of Salento, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Caruso","sequence":"additional","affiliation":[{"name":"Department of Surgery, Azienda Socio-Sanitaria Territoriale (ASST) Lodi, 26900 Lodi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4321-6525","authenticated-orcid":false,"given":"Marco","family":"Mercieri","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences and Translational Medicine, Sapienza University of Rome, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph V.","family":"Pergolizzi","sequence":"additional","affiliation":[{"name":"NEMA Research Inc., Naples, FL 34108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2464-0187","authenticated-orcid":false,"given":"Alan D.","family":"Kaye","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, LSU Health, Shreveport, LA 71115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Breve","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Temple University, Philadelphia, PA 19122, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9760-9394","authenticated-orcid":false,"given":"Alberto","family":"Corriero","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Medicine, University of Bari Aldo Moro, 70121 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Gharibo","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, NYU Grossman School of Medicine, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5228-3733","authenticated-orcid":false,"given":"Matteo Luigi Giuseppe","family":"Leoni","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences and Translational Medicine, Sapienza University of Rome, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Getie, A., Ayalneh, M., and Bimerew, M. 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