Unrestricted Weight Bearing as a Method for Assessment of Nociceptive Behavior in a Model of Tibiofemoral Osteoarthritis in Rats

Lise Skøtt Gregersen, Turid Røsland, Lars Arendt-Nielsen, Garth Whiteside, Michele Hummel

Center for Sensory-Motor Interaction, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg ?, Denmark.
Purdue Pharma LP, Cranbury, USA.

DOI: 10.4236/jbbs.2013.33030                

Abstract

Background: Novel preclinical models for prediction of osteoarthritis-like pain are necessary for the elucidation of osteoarthritis (OA) pathology and for assessment of novel analgesics. A widely used behavioral test in rat models of tibiofemoral OA is hind limb weight bearing (WB). However, this method evaluates WB in an unnaturally restricted manner. The aim of this study was therefore to characterize the Tekscan Pressure Measurement System as a means to assess OA-like tibiofemoral pain in rats by determination of plantar pressure distribution in a more natural and unrestricted position, defined as unrestricted WB. Methods: Intra-articular injections of 1 mg monosodium iodoacetate (MIA) or saline were administrated in the left hind knee of 84 male Sprague Dawley rats. Changes in unrestricted WB between ipsilateral and contralateral hindlimbs were determined. Morphine (5 mg/kg administered subcutaneously) and naproxen (60 mg/kg per-oral) were examined for their ability to reverse WB changes. Results: Changes in hind limb unrestricted WB were observed 14 (P < 0.05), 21 (P < 0.001) and 28 (P < 0.001) days post intra-articular injections of MIA compared to control. These alterations were attenuated by morphine 1 hour post administration compared to baseline but were not affected by naproxen. Conclusion: This study indicated that unrestricted WB assessed by the Tekscan system can be utilized as a clinically relevant method to assess aberrations in WB induced by intra-articular MIA injections in rodents. Therefore, this system may be useful for understanding the mechanisms of OA pain in humans and may also assist in the discovery of novel pharmacological agents.

Keywords

Osteoarthritis; Pain; Monosodium Iodoacetate; Unrestricted Weight Bearing; Morphine; Naproxen

Conflicts of Interest

The authors declare no conflicts of interest.

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