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.
Highlights
Many drugs used in clinical tumor chemotherapy induce peripheral neuropathy (PNP), which increases the burden of disease, but sometimes is dose limiting and detrimental to therapy [1]
In an additional set of experiments, we evaluated the effects of gabapentin treatment on gait parameters as well as mechanical allodynia
Dose-dense paclitaxel treatment induces a sensory polyneuropathy in C57BL/6J mice
Summary
Many drugs used in clinical tumor chemotherapy induce peripheral neuropathy (PNP), which increases the burden of disease, but sometimes is dose limiting and detrimental to therapy [1]. In animals mechanical allodynia can be assessed by determining the response threshold to a defined non-painful mechanical stimulus This is usually measured with a series of increasingly stiff von Frey filaments [4] or an electronic pressure-meter [5]. One caveat of detecting mechanical allodynia with the von Frey hair method is that the definition of a response may vary between investigators and many different ways of performing this test have been published [4,6,7]. This leads to difficulties in the interpretation of results from different groups and even between investigators within one laboratory
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