PHYSIOLOGICAL CHARACTERIZATION OF TAXOL-INDUCED LARGE FIBER SENSORY NEUROPATHY IN THE RAT

The cancer chemotherapeutic agent Taxol (paclitaxel) causes a dose-rel ated peripheral neuropathy in humans. We produced a dose-dependent lar ge-fiber sensory neuropathy, without detrimental effects on general he alth, in mature rats by using two intravenous injections 3 days apart. Tests of other dosing schedules demonstrated the dependence of the se verity of the neuropathy and of animal health on both the dose and the frequency of dosing. Pathologically, severe axonal degeneration and h ypomyelination were observed in sections of dorsal roots, whereas vent ral roots remained intact. Electrophysiologically, H-wave amplitudes i n the hindlimb and amplitudes of predominantly sensory compound nerve action potentials in the tail were reduced. These effects persisted fo r at least 4 months after treatment. Motor amplitudes were not affecte d, but both motor and sensory conduction velocities decreased. The abi lity of rats to remain balanced on a narrow beam was impaired, indicat ing proprioceptive deficits. Muscle strength, measured by hindlimb and forelimb grip strength, and heat nociception, measured by tail-flick and hindlimb withdrawal tests, were not affected by Taxol. This model of Taxol-induced neuropathy in mature rats, with minimal effects on ge neral health, parallels closely the clinical syndrome observed after T axol treatment in humans.