Weight bearing as a measure of disease progression and efficacy of anti-inflammatory compounds in a model of monosodium iodoacetate-induced osteoarthritis

被引:420
作者
Bove, SE [1 ]
Calcaterra, SL [1 ]
Brooker, RM [1 ]
Huber, CM [1 ]
Guzman, RE [1 ]
Juneau, PL [1 ]
Schrier, DJ [1 ]
Kilgore, KS [1 ]
机构
[1] Pfizer Global Res & Dev, Dept Inflammat Pharmacol, Ann Arbor Labs, Ann Arbor, MI 48105 USA
关键词
osteoarthritis; monosodium iodoacetate-induced arthritis; NSAIDs; acetaminophen;
D O I
10.1016/S1063-4584(03)00163-8
中图分类号
R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学(修复外科学)];
学科分类号
摘要
Objective: To describe an in vivo model in the rat in which change in weight distribution is used as a measure of disease progression and efficacy of acetaminophen and two nonsteroidal anti-inflammatory drugs (NSAIDs) in a model of monosodium iodoacetate (MIA)-induced osteoarthritis (OA). Methods: Intra-articular injections of MIA and saline were administered to male Wistar rats (175-200 g) into the right and left knee joints, respectively. Changes in hind paw weight distribution between the right (osteoarthritic) and left (contralateral control) limbs were utilized as an index of joint discomfort. Acetaminophen and two archetypal, orally administered NSAIDs, naproxen and rofecoxib, were examined for their ability to decrease MIA-induced change in weight distribution. Results: A concentration-dependent increase in change in hind paw weight distribution was noted after intra-articular injection of MIA. Both naproxen and rofecoxib demonstrated the capacity to significantly (P<0.05) decrease hind paw weight distribution in a dose-dependent fashion, indicating that the change in weight distribution associated with MIA injection is susceptible to pharmacological intervention. Conclusion: The determination of differences in hind paw weight distribution in the rat MIA model of OA is a technically straightforward, reproducible method that is predictive of the effects of anti-inflammatory and analgesic agents. This system may be useful for the discovery of novel pharmacologic agents in human OA. (C) 2003 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:821 / 830
页数:10
相关论文
共 32 条
[1]   Animal models of arthritis: Relevance to human disease [J].
Bendele, A ;
McComb, J ;
Gould, T ;
McAbee, T ;
Sennello, G ;
Chlipala, E ;
Guy, M .
TOXICOLOGIC PATHOLOGY, 1999, 27 (01) :134-142
[2]  
Carson F. L., 1997, HISTOTECHNOLOGY SELF
[3]   Gait analysis in a rat model of osteoarthrosis [J].
Clarke, KA ;
Heitmeyer, SA ;
Smith, AG ;
Taiwo, YO .
PHYSIOLOGY & BEHAVIOR, 1997, 62 (05) :951-954
[4]  
DIPIRO JT, 1993, PHARM PATHOPHYSIOLOG
[5]  
DUNHAM J, 1993, INT J EXP PATHOL, V74, P283
[7]  
Gencosmanoglu BE, 2001, RES EXP MED, V200, P215
[8]   Vascular mechanisms in osteoarthritis [J].
Ghosh, P ;
Cheras, PA .
BEST PRACTICE & RESEARCH IN CLINICAL RHEUMATOLOGY, 2001, 15 (05) :693-709
[9]   Mono-iodoacetate-induced experimental osteoarthritis - A dose-response study of loss of mobility, morphology, and biochemistry [J].
Guingamp, C ;
GegoutPottie, P ;
Philippe, L ;
Terlain, B ;
Netter, P ;
Gillet, P .
ARTHRITIS AND RHEUMATISM, 1997, 40 (09) :1670-1679
[10]  
GUZMAN RT, IN PRESS TOXICOL PAT