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

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.

SUBMITTER: Huehnchen P

PROVIDER: S-EPMC3797113 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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

Huehnchen Petra P Boehmerle Wolfgang W Endres Matthias M

PloS one 20131015 10

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, auto ...[more]

PMID: 24143194

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Project description:Evaluation of functional outcome is widely used across species to assess the recovery process following various pathological conditions, including spinal cord injury, musculo-skeletal injury, mithochondrial disease, neuropathic cancer, Huntington's disease, chronic pain, cortical lesion, and olivocerebellar degeneration among others. The Stroke Therapy Academic Industry Roundtable (STAIR) recommends multiple endpoints for behavioral studies in pre-clinical stroke research, to demonstrate their clinical relevance. One of the more challenging tasks in experimental stroke research is measuring long-term functional outcome in mice. It is, however, becoming more important, since transgenic mice are increasingly used for modeling human neurological disorders. Using CatWalk, we characterized long-lasting gait/locomotion deficits following mouse distal middle cerebral artery occlusion (dMCAO). The post-dMCAO assessment was performed at 7, 14, 21, and 28days after experimental ischemia. When compared to sham-operated mice, dMCAO animals displayed a statistically significant decrease in Spatial parameters (such as Paw Area), while the Temporal parameters (Stand, Initial and Terminal Dual Stances) were significantly increased for three weeks after surgery. Kinetic parameters were significantly decreased in dMCAO animals at 7days after dMCAO. The Interlimb coordination group of parameters displayed the strongest deficits at 21days. While CatWalk variables were altered in all paws, the degree of change was greatest for the parameters measured from the Right Front Paw (contralateral to the lesion). All parameters measured in dMCAO and Sham-operated groups reached similar levels at four weeks after the experimental insult, which reflects a spontaneous post-ischemic recovery. Based on our investigation, we conclude that CatWalk represents a relevant and sensitive analysis, which allows long-term characterization of animal functional recovery in the dMCAO model of experimental ischemia.

Dataset Information

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

Publications

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

Similar Datasets

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