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Peripheral neuropathy caused by cytotoxic drugs is increasingly becoming a dose limiting problem in cancer treatment. Cisplatin is a chemotherapeutic agent that is used extensively in the treatment of several types of cancer including bladder, testicular and ovarian tumors. The mechanism of nerve injury caused by the alkylating agent cisplatin is not yet well known. The drug accumulates in DRG leading the nucleolar damage and alterations in peptide content. Clinical manifestations of cisplatin neuropathy are focused on the sensory and autonomic systems with proprioception being most markedly affected, indicating particular sensitivity of large fibers.
In rat (Dark-Agouti) model of cisplatin-induced peripheral neuropathy, sensory dysfunction is detected by electromyographical and behavioral measurements. Cisplatin is given intraperitoneally twice a week for 4 week at the dose of 2 mg/kg.
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Compound testing addresses the effect of chronic treatment of cisplatin-intoxicated rats (typically starting the same day as cisplatin administration) :
- protection against nerve dysfunction and recovery of nerve function (electrophysiology measures)
- protection against loss of sensitivity and recovery of sensitivity (hot plate 52°C test)
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Loss of thermal sensitivity in cisplatin-intoxicated rats.
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Reduction of SNCV (sensory nerve conduction velocity) in cisplatin-intoxicated rats.
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ROWINSKI E.K and DONEHOWER R.C. 1991. The clinical pharmacology and use of antimicrotubule agents in cancer chemotherapeutics. Pharmacol. Ther. 52 : 35-84.
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VERDU E, VILCHES JJ, RODRIGUEZ GJ, CEBALLOS D, VALERO A and NAVARRO X. 1999. Physiological and immunohistochemical characterization of cisplatin-induced neuropathy in mice. Muscle and Nerve. 22 : 329-340.
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BOYLE FM, WHEELER HR and SHENFIELD GM. 1999. Amelioration of experimental cisplatin and paclitaxel neuropathy with glutamate. J. Neuro-oncology. 41 : 107-116.
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KRARUP-HANSEN A, RIETZ B, KRARUP C, HEYDORN K, RORTH M., SCHMALBRUCH H. 1999. Histology and platinum content of sensory ganglia and sural nerves in patients treated with cisplatin and carboplatin : an autopsy study. Neuropathol Appl Neurobiol. 25 : 29-40.
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