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
Department of Inflammation Biology, Pfizer Global Research and Development, Michigan Laboratories, Ann Arbor, MI 48105, USA.
Osteoarthritis Cartilage. 2006 Oct;14(10):1041-8. doi: 10.1016/j.joca.2006.05.001. Epub 2006 Jun 12.
In the present study, we sought to develop/characterize the pain profile of a rat model of surgically induced osteoarthritis (OA).
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.
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 (100mg/kg, PO, day 21 post surgery) significantly attenuated the change in HPWD, however, only gabapentin significantly decreased tactile allodynia.
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.
在本研究中，我们试图建立/描述手术诱导性骨关节炎（OA）大鼠模型的疼痛特征。
通过切断雄性Lewis大鼠（200 - 225 g）股骨 - 胫骨关节的内侧副韧带和内侧半月板，手术诱导OA。为了描述疼痛特征，评估动物后爪重量分布（HPWD）的变化、机械性异常性疼痛的发展以及热和机械性痛觉过敏的存在。检测罗非昔布和加巴喷丁减轻重量分布变化和触觉异常性疼痛的能力。
切断雄性Lewis大鼠的内侧副韧带和内侧半月板导致后爪负重迅速（<3天）变化，并出现触觉异常性疼痛（继发性痛觉过敏）。然而，对热痛觉过敏或机械性痛觉过敏没有明显影响。单剂量罗非昔布（10 mg/kg，口服，术后第21天）或加巴喷丁（100mg/kg，口服，术后第21天）治疗可显著减轻HPWD的变化，然而，只有加巴喷丁能显著减轻触觉异常性疼痛。
大鼠内侧半月板撕裂（MMT）模型模拟了伤害感受性和神经性OA疼痛，并且对常用于OA疼痛的选择性环氧化酶 - 2（COX - 2）抑制剂（罗非昔布）和广泛用于神经性疼痛的药物（加巴喷丁）均有反应。因此，大鼠MMT模型可能代表一种预测工具，用于开发治疗与OA相关症状的药物干预措施。
