The chemotherapeutic oxaliplatin alters voltage-gated Na+ channel kineticson rat sensory neurons

The chemotherapeutic oxaliplatin causes a sensory-motor neuropathy with pre dominantly hyperpathic symptoms. The mechanism underlying this hyperexcitab ility was investigated using rat sensory nerve preparations, dorsal root ga nglia and hippocampal neurons. Oxaliplatin resulted in an increase of the a mplitude and duration of compound action potentials. It lengthened the refr actory period of peripheral nerves suggesting an interaction with voltage-g ated Na+ channels. Application of oxaliplatin to dorsal root ganglion neuro ns resulted in an increase of the Na+ current, a block of the maximal ampli tude and a shift of the voltage-response relationship towards more negative membrane potentials. The effect was detectable on 13 of 18 tested cells. T his observation, together with the absence of any effect on Na+ currents of hippocampal neurons, suggests that the interaction of oxaliplatin is restr icted to one or more channel subtypes. The effect of oxaliplatin could be a ntagonised by the Na+ channel blocker carbamazepine which could be used to reduce side effects of oxaliplatin therapy in patients. (C) 2000 Elsevier S cience B.V. All rights reserved.