S-47 Clinical and Experimental Rheumatology 2017 Departments of Pharmacology and Anaesthesia, Pain Management & Perioperative Medicine, Dalhousie University, Halifax, Canada. Melissa O’Brien*, Holly T. Philpott*, Jason J. McDougall, *Co-frst authors Please address correspondence to: Dr Jason J. McDougall, Departments of Pharmacology and Anaesthesia, Pain Management and Perioperative Medicine, Dalhousie University, 5850 College Street, Halifax, Nova Scotia, B3H 4R2, Canada. E-mail: jason.mcdougall@dal.ca Received and accepted on September 9, 2017. Clin Exp Rheumatol 2017; 35 (Suppl. 107): S47-S52. © Copyright CliniCal and ExpErimEntal rhEumatology 2017. Key words: arthritis, animal models of disease, ageing, animal behaviour, electrophysiology, joint injury, nervous system, neuropathic pain, obesity. Competing interests: none declared. ABSTRACT Osteoarthritis (OA) is the most preva- lent musculoskeletal disease world- wide. Chronic pain remains the fore- most concern of OA patients and is poorly controlled by available phar- macotherapies. Current preclinical research, which aims to develop anal- gesics better suited for OA, is largely dependent on animal models and labo- ratory pain testing. This review sum- marises commonly used small animal models for studying experimental OA, including their benefts and limitations. Also discussed are a variety of vali- dated methods for studying pain within these models. Introduction Osteoarthritis (OA) is a multifaceted musculoskeletal disease which affects up to 50% of people aged 65 and over worldwide (1). OA is characterised by the inability of a damaged joint to launch an effective healing response. The foremost concern of OA patients is the alleviation of chronic pain which is not well controlled by current pharma- cotherapies. The frst line drug therapy for OA pain are the non-steroidal anti- infammatory drugs (NSAIDs). While these drugs are effective for acute pain, their analgesic capacity diminishes for the long-term treatment of OA pain while their risk of causing adverse side effects increases (2). The develop- ment of highly targeted analgesics for OA pain is crucial, but is hampered by poorly understood mechanisms of OA pain. To elucidate the pathogenesis of OA pain further, translatable animal models and valid pain assessment tech- niques are required. Animal models of osteoarthritis Spontaneous models • Dunkin Hartley spontaneous OA Mice, rabbits, guinea pigs, dogs, sheep, and horses naturally develop OA as they age. The most commonly studied of these animals is the Dunkin Hartley guinea pig which exhibits spontaneous OA that is remarkably similar to that in humans. The earliest changes in joint structure can be seen when animals are approximately 3-months old and by 12-months to 2 years severe medial de- generation of the knee joints are present (3). The relationship between joint dam- age and nociception was elegantly ex- plored in these animals using histopa- thology and electrophysiology where it was discovered that nociception did not correlate with joint damage in this model of OA (4). The beneft of using this model is the natural progression of OA with age, which is similar to the hu- man condition. Limitations include the long experimental time needed for OA development which in turn elevates the cost of experimentation. The lethargic and obese nature of these animals also precludes them for effective pain be- havioural assessment. • Obesity and arthritis Obesity has been identifed as a major risk factor for OA of the knee, but has also been implicated in hip and hand OA (5, 6). Obesity is associated with a chronic infammatory state with the overproduction of proinfammatory molecules. In addition, overloading the joints contributes to the pathogenesis and progression of OA in these animals. Griffn et al. examined various infam- matory, biomechanical, and osteoar- thritic changes in mice that were fed a high-fat diet for 45 weeks. This high-fat diet induced greater OA changes such as increased proteoglycan loss, de- creased musculoskeletal performance, and hyperalgesia to a thermal stimulus compared to control animals receiving a normal diet (7). These studies also re- vealed a correlation between severity of knee osteoarthritis and serum levels of leptin adiponectin, and IL-1α (7). Often preclinical models do not inte- grate risk factors and comorbidities, but by using a diet-induced obesity model it Understanding osteoarthritis pain through animal models M. O’Brien, H.T. Philpott, J.J. McDougall