Selected Ion Channels in Chemotherapy-Induced Peripheral Neuropathy: Mechanisms and Translational Limits

Chemotherapy-induced peripheral neuropathy (CIPN) combines abnormal sensory firing with neuronal and axonal injury. This critical narrative review focuses on selected voltage-gated sodium, calcium, and Kv7 potassium channels and transient receptor potential channels in chemotherapy-specific systems and human studies. Acute modulation is distinguished from altered channel abundance or localization and persistent remodeling. Human axonal-excitability studies support membrane dysfunction during acute oxaliplatin neurotoxicity but do not identify a sodium-channel subtype. Experimental studies identify changes in trafficking, stimulus sensitivity, and current that vary by time and compartment. Clinical analgesia does not itself demonstrate channel engagement or axonal protection. Duloxetine provides a symptomatic benchmark; results for channel-directed drugs and cannabinoid formulations remain inconsistent or design-limited. Natural products are treated as defined pharmacological examples, not as ranked candidates. A six-domain reporting template links target identity, potency, exposure, selectivity, CIPN context, and safety without assigning a composite score or evidence grade. Translation requires matching channel pharmacology to achievable unbound exposure and testing symptom relief separately from preservation of axons and protective sensation.