Surgically induced osteoarthritis in the rat results in the development of both osteoarthritis-like joint pain and secondary hyperalgesia

被引:128
作者
Bove, S. E.
Laemont, K. D.
Brooker, R. M.
Osborn, M. N.
Sanchez, B. M.
Guzman, R. E.
Hook, K. E.
Juneau, P. L.
Connor, J. R.
Kilgore, K. S.
机构
[1] Pfizer Global Res & Dev, Michigan Labs, Dept Inflammat Biol, Ann Arbor, MI 48105 USA
[2] Pfizer Global Res & Dev, Michigan Labs, Dept Safety Sci, Ann Arbor, MI 48105 USA
[3] Pfizer Global Res & Dev, Michigan Labs, Dept Nonclin Stat, Ann Arbor, MI 48105 USA
[4] Pfizer Global Res & Dev, St Louis Labs, Dept Inflammatory Mediators, Chesterfield, MO 63017 USA
关键词
osteoarthritis; medial meniscal tear; secondary hyperalgesia; COX-2; inhibitor; gabapentin; rat; allodynia;
D O I
10.1016/j.joca.2006.05.001
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: In the present study, we sought to develop/characterize the pain profile of a rat model of surgically induced osteoarthritis (OA) Methods: OA was surgically induced in male Lewis rats (200-225 g) by transection of the medial collateral ligament and medial meniscus of the femoro-tibial joint. In order to characterize the pain profile, animals were assessed for a change in hind paw weight distribution (HPWD), development of mechanical allodynia, and the presence of thermal and mechanical hyperalgesia. Rofecoxib and gabapentin were examined for their ability to decrease change in weight distribution and tactile allodynia. Results: Transection of the medial collateral ligament and medial meniscus of male Lewis rats resulted in rapid (<3 days) changes in hind paw weight bearing and the development of tactile allodynia (secondary hyperalgesia). There was, however, no appreciable effect on thermal hyperalgesia or mechanical hyperalgesia. Treatment with a single dose of rofecoxib (10 mg/kg, PO, day 21 post surgery) or gabapentin (100 mg/kg, PO, day 21 post surgery) significantly attenuated the change in HPWD, however, only gabapentin significantly decreased tactile allodynia. Conclusion: The rat medial meniscal tear (MMT) model mimics both nociceptive and neuropathic OA pain and is responsive to both a selective cylooxygenase-2 (COX-2) inhibitor commonly utilized for OA pain (rofecoxib) and a widely prescribed drug for neuropathic pain (gabapentin). The rat MMT model may therefore represent a predictive tool for the development of pharmacologic interventions for the treatment of the symptoms associated with OA. (C) 2006 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:1041 / 1048
页数:8
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