Dose effects of Oxaliplatin on persistent and transient na+ conductances and the development of neurotoxicity

Background Oxaliplatin, a platinum-based chemotherapy utilised in the treatment of colorectal cancer, produces two forms of neurotoxicity- acute sensorimotor neuropathic symptoms and a dose-limiting chronic sensory neuropathy. Given that a Na+ channelopathy has been proposed as the mechanism underlying acute oxaliplatin-induced neuropathy, the present study aimed to determine specific mechanisms of Na+ channel dysfunction. Methodology/Principal Findings Specifically the function of transient and persistent Na+ currents were followed during treatment and were investigated in relation to oxaliplatin dose level. Eighteen patients were assessed before and after a single oxaliplatin infusion with motor and sensory axonal excitability studies performed on the median nerve at the wrist. While refractoriness (associated with Na+ channel inactivation) was significantly altered post-oxaliplatin infusion in both motor (Pre: 31.7¡À6.4%; Post: 68.8¡À14.5%; P¡Ü.001) and sensory axons (Pre: 31.4¡À5.4%; Post: 21.4¡À5.5%; P