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Open Access Research article

Gait changes precede overt arthritis and strongly correlate with symptoms and histopathological events in pristane-induced arthritis

Markus H Hoffmann1*, Rudolf Hopf2, Birgit Niederreiter1, Heinz Redl2, Josef S Smolen1 and Günter Steiner1

Author Affiliations

1 Division of Rheumatology, Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria

2 Ludwig Boltzmann Institute for Experimental and Clinical Traumatology in the AUVA Research center for Traumatology and Austrian Cluster for Tissue Regeneration, Donaueschingenstrasse 13, A-1200 Vienna, Austria

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Arthritis Research & Therapy 2010, 12:R41  doi:10.1186/ar2950

Published: 11 March 2010

Abstract

Introduction

Pristane-induced arthritis (PIA) in the rat has been described as an animal model of inflammatory arthritis which exhibits features similar to rheumatoid arthritis in humans, such as a chronic, destructive, and symmetrical involvement of peripheral joints. However, so far little is known about the earliest inflammatory events and their influence on locomotor behaviour during the course of PIA. To investigate this issue a detailed analysis of the pathologic changes occurring during the prodromal and early stages of PIA was performed.

Methods

Arthritis was induced in DA.rats by injection of 150 μl 2,6,10,4-tetramethyl-pentadecane (pristane) at the base of the tail and changes in locomotor behaviour of the affected paws were monitored using the CatWalk quantitative gait analysis system. The pathologic events occurring in the joints of pristane-injected animals were studied before onset, at onset, and during acute phase of arthritis by histological methods.

Results

Gait analysis revealed that changes in locomotion such as reduced paw print areas and stance phase time are already apparent before the onset of clinically discernible arthritis symptoms (erythema, paw swelling) and correlate with PIA scores. In agreement with these findings, inflammatory tenosynovitis could be observed by histology already before the onset of erythema and swelling of the respective paws. In the most heavily affected rats also irregularities in step sequence patterns occurred A kinetic analysis of clinical and histological findings demonstrated that gait changes precede the pathological changes occurring during the acute phase of pristane-induced arthritis.

Conclusions

Gait analysis allows for pinpointing the initial inflammatory changes in experimental arthritis models such as pristane-induced arthritis. Analysis of early clinically relevant symptoms in arthritis models may facilitate the search for novel therapeutics to interfere with pain, inflammation and joint destruction in patients suffering from inflammatory arthritis.