ADVANCES IN THE PATHOPHYSIOLOGY AND MANAGEMENT OF CANCER PAIN: A SCOPING REVIEW

Y. Tran Van¹, A. Paladini², V.P. Pham¹, A.A. Al Alwany³, G. Farì⁴, A. Caruso⁵, M. Mercieri⁶, M.L.G. Leoni⁷, J.V. Pergolizzi⁸, A.D. Kaye⁹, F. Breve¹⁰, A. Corriero¹¹, C. Gharibo¹², G. Varrassi¹³ | ¹Department of Biomedical Engineering, International University, Vietnam National University, Ho Chi Minh City, Vietnam; ²Department of Life, Health and Environmental Sciences, University of L'Aquila, Italy; ³College of Medicine, University of Baghdad, Iraq; ⁴Department of Experimental Medicine (Di.Me.S.), University of Salento, Lecce, Italy; ⁶Department of Surgery, ASST Lodi, Lodi, Italy; ⁷Department of Medical and Surgical Sciences and Translational Medicine, Sapienza University of Rome, Italy; ⁸NEMA Research Inc., Naples, FL, USA; ⁹Department of Anesthesiology, LSU Health, Shreveport, LA, USA; ¹⁰School of Pharmacy, Temple University, Philadelphia, PA, USA; ¹¹Department of Interdisciplinary Medicine, University of Bari "Aldo Moro", Bari, Italy; ¹²Department of Anesthesiology, NYU Grossman School of Medicine, New York, NY, USA; ¹³Fondazione Paolo Procacci, Rome, Italy

Background and Aims. Cancer pain affects 55–95% 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–neuron–immune 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.