Objective: To review the use of animal models of osteoarthritis (OA) with regard to their utility for investigation of the mechanisms and regulation of structural pathology and pain.

Methods: PubMed searches were conducted using separate clusters of terms to retrieve articles on (i) models of structural joint damage in genetically-modified (GM) mice, and (ii) models of OA joint pain. The papers were reviewed to investigate whether there was evidence that the research outcome was dependent on the model used.

Results: Out of a total of 109 separate GM mice strains identified in which an effect on OA was reported, 15 had been studied using more than one arthritis model. In 10/15 the same effect of the GM on arthritis was reported in at least two different models. In 5/15 the effect of the GM on arthritis structural pathology was different, and sometimes opposite, when comparing two or more induction methods. A total of 112 publications were retrieved in which pain/disability was examined in a model suggested to represent OA. The induction methods used most commonly to study "OA pain" were distinct from those most often used to investigate the pathophysiology and regulation of structural joint damage. Four papers directly comparing pain mechanisms in different models were identified, with 3/4 describing differences in nociceptive pathways.

Conclusions: The available data indicates that the molecular mechanisms of both joint structural damage and pain may be distinct in animal models of OA induced or initiated by different means. This suggests the need to continue using multiple OA animal models but that the subsequent interpretation of the data and its extrapolation to the human condition must be more precise.