Assessment of paclitaxel induced sensory polyneuropathy with "Catwalk" automated gait analysis in mice

PLoS One. 2013 Oct 15;8(10):e76772. doi: 10.1371/journal.pone.0076772. eCollection 2013.

Abstract

Neuropathic pain as a symptom of sensory nerve damage is a frequent side effect of chemotherapy. The most common behavioral observation in animal models of chemotherapy induced polyneuropathy is the development of mechanical allodynia, which is quantified with von Frey filaments. The data from one study, however, cannot be easily compared with other studies owing to influences of environmental factors, inter-rater variability and differences in test paradigms. To overcome these limitations, automated quantitative gait analysis was proposed as an alternative, but its usefulness for assessing animals suffering from polyneuropathy has remained unclear. In the present study, we used a novel mouse model of paclitaxel induced polyneuropathy to compare results from electrophysiology and the von Frey method to gait alterations measured with the Catwalk test. To mimic recently improved clinical treatment strategies of gynecological malignancies, we established a mouse model of dose-dense paclitaxel therapy on the common C57Bl/6 background. In this model paclitaxel treated animals developed mechanical allodynia as well as reduced caudal sensory nerve action potential amplitudes indicative of a sensory polyneuropathy. Gait analysis with the Catwalk method detected distinct alterations of gait parameters in animals suffering from sensory neuropathy, revealing a minimized contact of the hind paws with the floor. Treatment of mechanical allodynia with gabapentin improved altered dynamic gait parameters. This study establishes a novel mouse model for investigating the side effects of dose-dense paclitaxel therapy and underlines the usefulness of automated gait analysis as an additional easy-to-use objective test for evaluating painful sensory polyneuropathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / pharmacology
  • Animals
  • Antineoplastic Agents / adverse effects*
  • Automation
  • Cyclohexanecarboxylic Acids / pharmacology
  • Dose-Response Relationship, Drug
  • Gabapentin
  • Gait / drug effects*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Paclitaxel / adverse effects*
  • Peripheral Nervous System / drug effects*
  • Peripheral Nervous System / physiopathology
  • Polyneuropathies / chemically induced*
  • Polyneuropathies / physiopathology*
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • Amines
  • Antineoplastic Agents
  • Cyclohexanecarboxylic Acids
  • gamma-Aminobutyric Acid
  • Gabapentin
  • Paclitaxel

Grant support

The research leading to these results has received funding for the procurement of equipment and consumables from the federal ministry of education and research via the grant center for stroke research Berlin (01 EO 0801), the Volkswagen foundation (Lichtenberg program to Matthias Endres), and Deutsche Forschungsgemeinschaft DFG (NeuroCure). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.