title: The Monoiodoacetate Model of Osteoarthritis Pain in the Mouse.
abstract: A major symptom of patients with osteoarthritis (OA) is pain that is triggered by peripheral as well as central changes within the pain pathways. The current treatments for OA pain such as NSAIDS or opiates are neither sufficiently effective nor devoid of detrimental side effects. Animal models of OA are being developed to improve our understanding of OA-related pain mechanisms and define novel pharmacological targets for therapy. Currently available models of OA in rodents include surgical and chemical interventions into one knee joint. The monoiodoacetate (MIA) model has become a standard for modelling joint disruption in OA in both rats and mice. The model, which is easier to perform in the rat, involves injection of MIA into a knee joint that induces rapid pain-like responses in the ipsilateral limb, the level of which can be controlled by injection of different doses. Intra-articular injection of MIA disrupts chondrocyte glycolysis by inhibiting glyceraldehyde-3-phosphatase dehydrogenase and results in chondrocyte death, neovascularization, subchondral bone necrosis and collapse, as well as inflammation. The morphological changes of the articular cartilage and bone disruption are reflective of some aspects of patient pathology. Along with joint damage, MIA injection induces referred mechanical sensitivity in the ipsilateral hind paw and weight bearing deficits that are measurable and quantifiable. These behavioral changes resemble some of the symptoms reported by the patient population, thereby validating the MIA injection in the knee as a useful and relevant pre-clinical model of OA pain. The aim of this article is to describe the methodology of intra-articular injections of MIA and the behavioral recordings of the associated development of hypersensitivity with a mind to highlight the necessary steps to give consistent and reliable recordings.
authors.affiliation: Wolfson Centre for Age Related Diseases, King's College London.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pitcher
authors.affiliation: Wolfson Centre for Age Related Diseases, King's College London.
authors.forename: João
authors.initials: J
authors.lastname: Sousa-Valente
authors.affiliation: Wolfson Centre for Age Related Diseases, King's College London; marzia.malcangio@kcl.ac.uk.
authors.forename: Marzia
authors.initials: M
authors.lastname: Malcangio
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000473:pathology*; D001522:Behavior, Animal; D002358:Cartilage, Articular / Q000473:pathology; D019902:Chondrocytes / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000633:toxicity; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology; D007249:Inflammation / Q000473:pathology; D007270:Injections, Intra-Articular; D019807:Iodoacetic Acid / Q000633:toxicity; D007719:Knee Joint / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D020370:Osteoarthritis, Knee / Q000139:chemically induced / Q000473:pathology*; D010146:Pain / Q000139:chemically induced / Q000473:pathology*; D017288:Pain Threshold; D016474:Weight-Bearing / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D019807:Iodoacetic Acid