A study by Wu and colleagues (2001)

A study by Wu and colleagues (2001) identified a
mutation in a voltage-gated sodium channel in a family with
cold-aggravated myotonia.
This mutation led to functional
defects of fast inactivation of the sodium channels
presumably provoking myotonic spells (Wu et al 2001). It
has been shown in rat models that oxaliplatin alters voltagegated
sodium channels.
The effects of oxaliplatin were studied on rat nerve preparations by Aldersberger et al
(2000), who exposed rat nerves to oxaliplatin.
They observed an increase in amplitude and duration of compound action
potentials and prolongation of the refractory period of
peripheral nerves. They also noticed that the potassium
current was not altered with the addition of oxaliplatin after
sodium channels were blocked using tetrodotoxin. This was
an important finding, which suggested that the alterations
in the action potential were related to sodium and not
potassium channels. The authors implicate that oxalate, a
known calcium chelator, may play a role in the sodium
channel interaction by chelating calcium; however, they
found no difference in the antagonistic effect of oxaliplatin
on sodium channels at low calcium concentrations
(Aldersberger et al 2000).
The theory that an oxalate affects the sodium channels
has been entertained by other researchers as well. Oxalate
is released intracellularly from oxaliplatin by bicarbonate
ions. Oxalate and 1,2-bis(2-aminophenoxy)ethane-
N,N,N´,N´-tetraacetic acid (BAPTA), another calcium
chelator, have produced effects on inward sodium currents
in invertebrate models similar to those seen with oxaliplatin
(Grolleau et al 2001). See Figure 1.
Unlike the acute transient neuropathy, the cumulative
toxicity of oxaliplatin appears to be related to direct toxicity
to the nerve. Morphological changes have been evident in
dorsal root ganglia in rats treated with cumulative doses of
oxaliplatin intraperitoneally. The treated rats had evidence
of nuclear, nucloeolar, and somatic size reduction on
microscopic examination of the dorsal root ganglia
(Cavaletti et al 2001). These studies have set the framework
for various treatments for oxaliplatin-induced neurotoxicity.