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Oxaliplatin causes selective atrophy of a subpopulation of dorsal root ganglion neurons without inducing cell loss
- Source :
- Cancer chemotherapy and pharmacology. 56(4)
- Publication Year :
- 2004
-
Abstract
- Peripheral neuropathy is induced by multiple doses of oxaliplatin and interferes with the clinical utility of the drug in patients with colorectal cancer. In this study, we sought to determine whether cell loss or selective neuronal damage was the basis for the peripheral neuropathy caused by oxaliplatin. Adult female rats were given 1.85 mg/kg oxaliplatin twice per week for 8 weeks. Nerve conduction and L5 dorsal root ganglia (DRG) were studied 1 week after the completion of all treatment. No mortality occurred during oxaliplatin treatment, but the rate of body weight gain was reduced compared to age-matched vehicle-treated controls. Oxaliplatin slowed conduction velocity and delayed conduction times in peripheral sensory nerves, without affecting central or motor nerve conduction. In L5 DRG, total numbers of neurons were unchanged by oxaliplatin, but there were significant reductions in neuronal size distribution, ganglion volume, average cell size and the relative frequency of large cells. In addition, the relative frequency of small DRG cells was increased by oxaliplatin. Oxaliplatin significantly altered the size distribution and average cell body area of the predominantly large parvalbumin-immunoreactive DRG neurons without affecting the frequency of parvalbumin staining. On the contrary, neither the staining frequency nor the size distribution of the predominantly small substance P-immunoreactive DRG neurons was changed by oxaliplatin. In conclusion, oxaliplatin causes selective atrophy of a subpopulation of DRG neurons with predominantly large parvalbumin-expressing cells without inducing neuronal loss. Because DRG cell body size and axonal conduction velocity are positively correlated, neuronal atrophy may be the morphological basis for the development of decreased sensory nerve conduction velocity that characterizes oxaliplatin-induced peripheral neuropathy.
- Subjects :
- Cancer Research
medicine.medical_specialty
Organoplatinum Compounds
Neural Conduction
Motor nerve
Antineoplastic Agents
Substance P
Toxicology
Nerve conduction velocity
Atrophy
Dorsal root ganglion
Decreased sensory nerve conduction velocity
Internal medicine
Ganglia, Spinal
Medicine
Animals
Pharmacology (medical)
Rats, Wistar
Pharmacology
business.industry
Peripheral Nervous System Diseases
Anatomy
medicine.disease
digestive system diseases
Oxaliplatin
Ganglion
Rats
Peripheral neuropathy
medicine.anatomical_structure
Endocrinology
Parvalbumins
nervous system
Oncology
Female
business
medicine.drug
Subjects
Details
- ISSN :
- 03445704
- Volume :
- 56
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Cancer chemotherapy and pharmacology
- Accession number :
- edsair.doi.dedup.....90eb45d2969b8d38daf408e1c1f1a280