Physiological characterization of taxol-induced large fiber sensory neuropathy in the rat

被引：111

作者：

Cliffer, KD ^{[1
]}

Siuciak, JA ^{[1
]}

Carson, SR ^{[1
]}

Radley, HE ^{[1
]}

Park, JS ^{[1
]}

Lewis, DR ^{[1
]}

Zlotchenko, E ^{[1
]}

Nguyen, T ^{[1
]}

Garcia, K ^{[1
]}

Tonra, JR ^{[1
]}

Stambler, N ^{[1
]}

Cedarbaum, JM ^{[1
]}

Bodine, SC ^{[1
]}

Lindsay, RM ^{[1
]}

DiStefano, PS ^{[1
]}

机构：

[1] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA

来源：

ANNALS OF NEUROLOGY | 1998年 / 43卷 / 01期

关键词：

D O I：

10.1002/ana.410430111

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

The cancer chemotherapeutic agent Taxol (paclitaxel) causes a dose-related peripheral neuropathy in humans. We produced a dose-dependent large-fiber sensory neuropathy, without detrimental effects on general health, in mature rats by using two intravenous injections 3 days apart. Tests of other dosing schedules demonstrated the dependence of the severity of the neuropathy and of animal health on both the dose and the frequency of dosing. Pathologically, severe axonal degeneration and hypomyelination were observed in sections of dorsal roots, whereas ventral roots remained intact. Electrophysiologically, H-wave amplitudes in the hindlimb and amplitudes of predominantly sensory compound nerve action potentials in the tail were reduced. These effects persisted for at least 4 months after treatment. Motor amplitudes were not affected, but both motor and sensory conduction velocities decreased. The ability of rats to remain balanced on a narrow beam was impaired, indicating 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 general health, parallels closely the clinical syndrome observed after Taxol treatment in humans.

引用

页码：46 / 55

页数：10

共 39 条

[1] NERVE GROWTH-FACTOR PREVENTS TOXIC NEUROPATHY IN MICE [J].