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Abstract Details

The Neurophysiology of Oxaliplatin Effects on Peripheral Nerve
Neuromuscular and Clinical Neurophysiology (EMG)
P4 - Poster Session 4 (5:30 PM-6:30 PM)
12-038
Determine the time course and concentration dependent effects of oxaliplatin on the nerve action potential.  
Oxaliplatin is an important chemotherapy drug whose major dose limiting side effect is peripheral neuropathy.   Understanding the effects of concentration and time of exposure of a nerve to oxaliplatin may help in developing strategies to reduce this toxicity.  
The in-vitro sciatic nerve model is used with rat sciatic nerve placed into a perfusion apparatus where the nerve microenvironment and the concentration of oxaliplatin can be carefully controlled.  Paired stimuli are provided to each nerve at 5Hz, the averaged NAP is digitized and recorded every 4 seconds.   The changes in the NAP over time in the absence of oxaliplatin and with three different infusions of oxaliplatin are determined and analyzed for statistically significant changes.  Maximum oxaliplatin concentrations of 9.3uM, 93uM and 208uM are studied.  At the end of the infusion the perfusate is replaced by a non-oxaliplatin containing solution.  
The most prominent changes in the NAP with the oxaliplatin infusion are prolongation in the duration of the NAP and prolonged NAP rise time as well as the loss in the amplitude the trough following the NAP peak.  Smaller change in the amplitude of the NAP peak are noted.  Changes in the NAP persist even after the oxaliplatin is removed from the perfusate.  The first changes in the NAP can be seen at concentrations as low as 0.46uM but effects rapidly increase as the concentration increases over 100uM.  .   
The changes in the NAP with oxaliplatin concentration are consistent with an effect on sodium channels.  The persistence of effects after oxaliplatin is removed from the perfusate suggests a strong interaction between oxaliplatin and sodium channels.  The in-vitro sciatic nerve model may be useful in testing treatments that could ameliorate the effects of oxaliplatin on the peripheral nerve
Authors/Disclosures
Mark M. Stecker, MD, FAAN
PRESENTER
No disclosure on file