Cancer Pain: Advances in Pathophysiology and Management

Dear Colleagues,

Cancer pain remains one of the most frequent and debilitating consequences of malignancy and is typically characterized by a multifaceted pathophysiology involving concurrent nociceptive, neuropathic, and often nociplastic mechanisms, constituting a paradigmatic form of mixed pain. Its biological underpinnings arise from tumor-induced tissue destruction, the release of pro-inflammatory mediators, nerve infiltration or compression, and treatment-related neurotoxicity. Emerging evidence further underscores the pivotal role of tumor–neuron–immune interactions, including cytokine-mediated sensitization and bidirectional neuro-immune signaling, in driving both peripheral and central sensitization. Optimal management, therefore, necessitates a mechanism-oriented, multidisciplinary strategy that integrates pharmacological and non-pharmacological interventions. Opioids and NSAIDs remain the foundation for moderate-to-severe cancer pain, complemented by the rational use of adjuvants such as gabapentinoids, antidepressants, corticosteroids, bisphosphonates, and other anti-resorptive agents. For refractory or anatomically complex presentations, interventional procedures, including targeted nerve blocks, neuromodulation techniques, and vertebral augmentation, offer additional therapeutic value. Early, systematic assessment and individualized multimodal care plans are essential to enhance analgesic efficacy, reduce treatment-related harms, and preserve quality of life. This Special Issue will highlight emerging insights and innovative approaches that may ultimately improve the management of cancer-related pain.

Prof. Dr. Giustino Varrassi
Dr. Matteo Luigi Giuseppe Leoni
Guest Editors

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