title: Development and pharmacological characterization of a rat model of osteoarthritis pain.
abstract: Osteoarthritis (OA) is an age-related joint disease characterized by degeneration of articular cartilage and is associated with chronic pain. Although several experimental models of OA have been employed to investigate the underlying etiologies of the disease, there has been relatively little investigation into development of animal models of OA to study the pain associated with the condition. In the present study, we investigated OA induced by injection of either iodoacetate or papain into the knee joint of rats, and assessed the joint degeneration with radiographic analyses and measured pain behavior using hind limb weight bearing. We found that injection of iodoacetate, but not papain, resulted in a chronic joint degeneration as measured by decreased bone mineral content and bone mineral density, necrosis of articular cartilage and osteophyte formation. These pathological changes were associated with pain that manifested as time- and concentration-dependent alterations in hind limb weight bearing. These alterations in hind limb weight bearing were reversed with morphine, but were not significantly affected by acute administration of either indomethacin or celecoxib. However, administration of 30 mg/kg celecoxib twice daily for 10 days resulted in a significant restoration of hind limb weight bearing. We conclude that the iodoacetate model of OA is a relevant animal model to study pain associated with OA, and can be used to test potential therapeutic agents.
authors.affiliation: Discovery Research, Purdue Pharma, L.P., 6 Cedarbrook Drive, Cranbury, NJ 08512, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Pomonis
authors.forename: Jamie M
authors.initials: JM
authors.lastname: Boulet
authors.forename: Susan L
authors.initials: SL
authors.lastname: Gottshall
authors.forename: Steve
authors.initials: S
authors.lastname: Phillips
authors.forename: Rani
authors.initials: R
authors.lastname: Sellers
authors.forename: Tracie
authors.initials: T
authors.lastname: Bunton
authors.forename: Katharine
authors.initials: K
authors.lastname: Walker
mesh_terms: D000477:Alkylating Agents; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D000068579:Celecoxib; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D006614:Hindlimb; D007213:Indomethacin / Q000494:pharmacology; D007270:Injections, Intra-Articular; D007461:Iodoacetates; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D020370:Osteoarthritis, Knee / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D010146:Pain / Q000188:drug therapy* / Q000473:pathology; D010206:Papain; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology; D016474:Weight-Bearing
chemical_list: D000477:Alkylating Agents; D000701:Analgesics, Opioid; D016861:Cyclooxygenase Inhibitors; D007461:Iodoacetates; D011720:Pyrazoles; D013449:Sulfonamides; D009020:Morphine; D010206:Papain; D000068579:Celecoxib; D007213:Indomethacin