Email updates

Keep up to date with the latest news and content from Molecular Pain and BioMed Central.

Open Access Highly Accessed Research

Multimodal assessment of painful peripheral neuropathy induced by chronic oxaliplatin-based chemotherapy in mice

Cynthia L Renn1*, Valentina A Carozzi2, Peter Rhee1, Danisha Gallop1, Susan G Dorsey1 and Guido Cavaletti2

Author Affiliations

1 School of Nursing, Center for Pain Studies, University of Maryland, Baltimore, MD, USA

2 Department of Neuroscience and Biomedical Technologies Department, University of Milan Bicocca, Monza (MB), Italy

For all author emails, please log on.

Molecular Pain 2011, 7:29  doi:10.1186/1744-8069-7-29

Published: 26 April 2011

Abstract

Background

A major clinical issue affecting 10-40% of cancer patients treated with oxaliplatin is severe peripheral neuropathy with symptoms including cold sensitivity and neuropathic pain. Rat models have been used to describe the pathological features of oxaliplatin-induced peripheral neuropathy; however, they are inadequate for parallel studies of oxaliplatin's antineoplastic activity and neurotoxicity because most cancer models are developed in mice. Thus, we characterized the effects of chronic, bi-weekly administration of oxaliplatin in BALB/c mice. We first studied oxaliplatin's effects on the peripheral nervous system by measuring caudal and digital nerve conduction velocities (NCV) followed by ultrastructural and morphometric analyses of dorsal root ganglia (DRG) and sciatic nerves. To further characterize the model, we examined nocifensive behavior and central nervous system excitability by in vivo electrophysiological recording of spinal dorsal horn (SDH) wide dynamic range neurons in oxaliplatin-treated mice

Results

We found significantly decreased NCV and action potential amplitude after oxaliplatin treatment along with neuronal atrophy and multinucleolated DRG neurons that have eccentric nucleoli. Oxaliplatin also induced significant mechanical allodynia and cold hyperalgesia, starting from the first week of treatment, and a significant increase in the activity of wide dynamic range neurons in the SDH.

Conclusions

Our findings demonstrate that chronic treatment with oxaliplatin produces neurotoxic changes in BALB/c mice, confirming that this model is a suitable tool to conduct further mechanistic studies of oxaliplatin-related antineoplastic activity, peripheral neurotoxicity and pain. Further, this model can be used for the preclinical discovery of new neuroprotective and analgesic compounds.

Keywords:
Oxaliplatin; peripheral neuropathy; cold hyperalgesia; mechanical allodynia; dorsal root ganglia; spinal dorsal horn; electrophysiology