Mechanisms of spinal glial activation in chemotherapy‐induced peripheral neuropathy: Focus on microglia and astrocytes

Abstract Chemotherapy‐induced peripheral neuropathy (CIPN) is a common complication in patients with malignant tumors during chemotherapy. The pathological mechanisms of CIPN remain unclear, and effective preventive and therapeutic strategies are still lacking, posing a major challenge in clinical practice. Aberrant activation of spinal glial cells, particularly microglia and astrocytes, is a key pathological hallmark of CIPN. Evidence from multiple animal models supports a causal link between glial activation and CIPN, suggesting that glial cells may serve as potential therapeutic targets. However, owing to the diversity of chemotherapy agents, the mechanisms of glial activation in CIPN differ and remain insufficiently characterized. This review takes spinal glial activation induced by peripheral nerve injury as its starting point, with a specific focus on microglia and astrocytes. It provides a systematic overview of their roles and mechanisms in CIPN caused by commonly used chemotherapeutic agents. The aim is to deepen understanding of CIPN pathogenesis and provide a foundation for developing targeted therapies.