Nerve growth factor prevents toxic neuropathy in mice.
Taxol is a promising new antitumor drug with therapeutic use that is limited by a toxic sensory neuropathy. Taxol is also cytotoxic to dorsal root ganglion neurons in vitro, but this effect is prevented by cotreatment with the trophic protein, nerve growth factor. We sought to develop an animal model and then to determine whether nerve growth factor can prevent taxol neuropathy in vivo. Administration of taxol to mice resulted in a profound sensory neuropathy characterized by decreases in dorsal root ganglion content of the peptide neurotransmitter, substance P, elevated threshold to thermally induced pain, and diminished amplitude of the compound action potential in the caudal nerve. Coadministration of nerve growth factor prevented all of these signs of neurotoxicity. These findings suggest that administration of nerve growth factor may prevent certain toxic sensory neuropathies.
Apfel
S C
SC
Department of Neurology, Albert Einstein College of Medicine, Bronx, NY.
Lipton
R B
RB
Arezzo
J C
JC
Kessler
J A
JA
D000470:Alkaloids / Q000633:toxicity*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D001522:Behavior, Animal / Q000187:drug effects; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D009414:Nerve Growth Factors / Q000627:therapeutic use*; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000503:physiopathology; D009431:Neural Conduction / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects; D017239:Paclitaxel; D011930:Reaction Time; D013373:Substance P / Q000032:analysis
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D009414:Nerve Growth Factors; D013373:Substance P; D017239:Paclitaxel