Persistent Chemotherapy-Induced Peripheral Neuropathy as a Chronic Cancer Pain Syndrome: Mechanisms, Therapeutic Limitations, and Future Directions.

Background/

Objectives

Chemotherapy-induced peripheral neuropathy (CIPN) is a common, dose-limiting complication of cancer therapy and a major contributor to chronic neuropathic pain among cancer survivors. Although traditionally managed as a treatment-related toxicity, persistent CIPN frequently persists long after chemotherapy completion and is increasingly recognized as a major survivorship and palliative care challenge. This review synthesizes current mechanistic, clinical, and translational evidence and reframes persistent CIPN as a chronic neuropathic cancer pain syndrome.

Methods

A narrative review of peer-reviewed literature was conducted using PubMed/MEDLINE, Embase, and the Cochrane Library, supplemented by manual review of key references and clinical guidelines. Emphasis was placed on mechanistic investigations, clinical management, survivorship, palliative care, and emerging therapeutic strategies relevant to CIPN.

Results

Current evidence suggests that persistent CIPN reflects a multifactorial chronic neuropathic pain state involving neuronal injury, mitochondrial dysfunction, oxidative stress, neuroimmune activation, and maladaptive nociceptive signaling. Existing pharmacologic therapies provide limited symptomatic benefit and largely fail to address the underlying biologic mechanisms that contribute to symptom persistence. Emerging approaches involving mitochondrial-targeted therapies, neuroimmune modulation, biomarker-guided risk stratification, and multimodal supportive care suggest the potential for earlier intervention and disease modification rather than symptom palliation alone.

Conclusions

Persistent CIPN should be conceptualized as a chronic neuropathic cancer pain syndrome rather than solely as a treatment-related toxicity. Future progress will likely require mechanism-informed therapeutic development, biologic stratification, earlier intervention, and survivorship-focused multidisciplinary care to improve long-term outcomes and quality of life in patients living with persistent CIPN.