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Open Access Research article

Videoradiographic analysis of the range of motion in unilateral experimental knee joint arthritis in rats

Michael K Boettger12*, Johannes Leuchtweis1, Hans-Georg Schaible1 and Manuela Schmidt3

  • * Corresponding author: Michael K Boettger mkboettger@gmx.de

  • † Equal contributors

Author Affiliations

1 Institute of Physiology I/Neurophysiology, University Hospital, Teichgraben 8, D-07743 Jena, Germany

2 Current address: Bayer Schering Pharma AG, Forschungszentrum Elberfeld, Aprather Weg 18 a, D-42113 Wuppertal, Germany

3 Institute of Systematic Zoology and Evolutionary Biology, Friedrich-Schiller-University, Erbertstrasse 1, D-07743 Jena, Germany

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Arthritis Research & Therapy 2011, 13:R79  doi:10.1186/ar3342

Published: 27 May 2011

Abstract

Introduction

The translational and predictive value of animal models highly depends on the validity of respective readout parameters. In arthritis research, there has been a shift from sole threshold testing for pain-related behavior, as well as from swelling and histology assessment for inflammation, toward an analysis of joint function as indicated, for instance, by an increasing number of studies on gait abnormalities. Clinically, the range of motion (ROM) of the affected joint plays a major role in diagnosis and the assessment of treatment benefits. This parameter, however, is only insufficiently detected by currently used analytic systems in animals.

Methods

Here we used high-resolution videoradiographic analysis to assess ROM in experimental knee joint arthritis in rats. This parameter is described during the 21-day course of antigen-induced arthritis in rats. Furthermore, the therapeutic effects of antinociceptive (morphine) and anti-inflammatory (dexamethasone) treatment on ROM are documented. To obtain additional information on the implications of ROM in animal models, correlations were performed to measure pain-related behavior and inflammation.

Results

The study animals showed a significant reduction in ROM of the inflamed knee joint in the acute phase of arthritis. This was accompanied by an increase in knee joint movement on the contralateral side, indicating a compensational mechanism. Both morphine and dexamethasone treatment increased and thus normalized ROM. Changes in ROM were further stage-dependently correlated with weight bearing and joint swelling, that is, with both pain-related behavior and signs of inflammation.

Conclusions

The dynamic ROM observed in freely moving rats in our model of knee joint arthritis might serve as a parameter for global disease activity and might thus represent a promising readout parameter for preclinical assessment regarding the overall efficacy not only of antiarthritic but also of antinociceptive compounds.

Keywords:
range of motion; rat; arthritis; mechanical thresholds; videoradiography; readout parameter; preclinical testing