Oxaliplatin-induced Hyperexcitation of Rat Sciatic Nerve Fibers: An Intra-axonal Study

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)

Volume 17, 14 Issues, 2017

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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Michelle Prudhomme
Institut de Chimie de Clermont-Ferrand
Université Clermont Auvergne

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Oxaliplatin-induced Hyperexcitation of Rat Sciatic Nerve Fibers: An Intra-axonal Study

Anti-Cancer Agents in Medicinal Chemistry, 13(2): 373-379.

Author(s): Alexia Kagiava, Efstratios K. Kosmidis and George Theophilidis.

Affiliation: School of Biology, Aristotle University of Thessaloniki, Thessaloniki, 54 124, Greece.


Oxaliplatin is an agent that is used extensively in gastrointestinal cancer chemotherapy. The agent's major dose-limiting toxicity is peripheral neuropathy that can manifest as a chronic or an acute syndrome. Oxaliplatin-induced acute neuropathy is purportedly caused by an alteration of the biophysical properties of voltage-gated sodium channels. However, sodium channel blockers have not been successful at preventing acute neuropathy in the clinical setting. We report intra-axonal recordings from the isolated rat sciatic nerve preparation under the effect of oxaliplatin. The depolarization phase of single action potentials remains intact with a duration of 0.52 ± 0.02 ms (n=68) before and 0.55 ± 0.01 ms (n=68) after 1-5 h of exposure to 150 μM oxaliplatin (unpaired t-test, P > 0.05) whereas there is a significant broadening of the repolarization phase (2.16 ± 0.10 ms, n=68, before and 5.90 ± 0.32 ms after, n=68, unpaired t-test, P < 0.05). Apart from changes in spike shape, oxaliplatin also had drastic concentration- and time-dependent effects on the firing responses of fibers to short stimuli. In the intra-axonal recordings, three groups of firing patterns were indentified. The first group shows bursting (internal frequency 90 - 130 Hz, n=88), the second shows a characteristic plateau (at -19.27±2.84 mV, n=31, with durations ranging from 45 - 140 ms depending on the exposure time), and the third combines a plateau and a bursting period. Our results implicate the voltage-gated potassium channels as additional oxaliplatin targets, opening up new perspectives for the pharmacological prevention of peripheral neuropathy.


Action potential, Colorectal cancer, Hyperexcitability, Intra-axonal recordings, Peripheral neuropathy, Oxaliplatin, Sciatic nerve fiber.

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Article Details

Volume: 13
Issue Number: 2
First Page: 373
Last Page: 379
Page Count: 7
DOI: 10.2174/1871520611313020023
Price: $58
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