Effects of repeated administration of low doses of cisplatin on the rat nervous system.

Cisplatin is a very effective antineoplastic drug. To date its major toxic dose-limiting effect is peripheral neuropathy. Whereas the clinical and neurophysiological features of cisplatin-induced neuropathy are fairly well known, its pathogenesis is still unclear. We treated a group of Wistar rats with low doses of cisplatin for 70 days in order to evaluate the light-microscopic and ultrastructural changes induced by chronic cisplatin administration in the spinal cord, spinal ganglia and peripheral nerves. Although the most striking pathological alterations were observed in the spinal ganglia neurons, initial axonal neuropathy was also demonstrated, whereas the spinal cord neurons were completely normal. Our findings further support the hypotheses that spinal ganglion neurons are the primary target of cisplatin peripheral neurotoxicity and that peripheral nerve damage is secondary to this neuronopathy.