Structural pathology in a rodent model of osteoarthritis is associated with neuropathic pain: Increased expression of ATF-3 and pharmacological characterisation
Structural pathology in a rodent model of osteoarthritis is associated with neuropathic pain: Increased expression of ATF-3 and pharmacological characterisation
复制标题
DOI：
10.1016/j.pain.2006.12.022
复制
发表时间：
2007-04-01
期刊：
影响因子：
7.4
通讯作者：
Read, Simon J.
中科院分区：
文献类型：
--
作者：
Ivanavicius, Stefan P.;Ball, Adrian D.;Read, Simon J.
大鼠膝关节关节内注射单碘乙酸酯（MIA）引起与骨关节炎（OA）相似的组织病理学。通常情况下，滑膜炎（1-3天）出现，随后关节软骨变薄，软骨下骨在8-14天以后出现病变。在行为上，观察到体重不对称，在早期而不是后期（第14天以上）时间点对抗炎药物敏感。由于软骨下骨有密集的神经支配，一个有趣的可能性是局灶性骨病理可能导致该模型中的神经病变。在雄性Wistar大鼠中，用激活转录因子(ATF)-3免疫荧光作为同侧膝关节腰(L)4和L5背根神经节神经损伤的标志。与生理盐水对照组相比，MIA治疗后L5第8天和第14天的atf -3免疫反应性显著升高（P < 0.05， Kruskal-Wallis和Mann-Whitney u检验）。此外，在另一项研究中，动物被口服给药（5ml /kg）、萘普生（0.3- 10mg /kg）、塞来昔布（1- 10mg /kg）、阿米替林（3- 30mg /kg）和加巴喷丁（10- 100mg /kg），并在mia后第14、21和28天评估负重不对称性。阿米替林和加巴喷丁高、中剂量组在所有时间点均观察到体重的显著分解（P < 0.05，方差分析，事后Bonferroni’s）。Vs剂量前测量)。萘普生（10 mg/kg）在第14天和第28天观察到短暂和微弱的作用，而塞来昔布没有明显的作用。总的来说，这些数据表明，这种假定的OA模型与膝关节L5神经支配区域的早期神经病变有关。(c) 2007年国际疼痛研究协会。Elsevier B.V.版权所有。
Intra-articular injection of mono-iodoacetate (MIA) in the rat knee joint induces a histopathology with similarities to osteoarthritis (OA). Typically, a synovitis (days 1-3) is observed followed by thinning of articular cartilage and subsequent lesion of subchondral bone at days 8-14 onwards. Behaviourally, weight-bearing asymmetry is observed, which is sensitive to anti-inflammatory pharmacology at early but not later (days 14+) time points. As subchondral bone is densely innervated, an intriguing possibility is that focal bone pathology may cause neuropathy in this model. In male Wistar rats, activating transcription factor (ATF)-3-immunofluorescence was used as a marker of nerve injury in lumber (L)4 and L5 dorsal root ganglia of the ipsilateral knee. Significantly increased ATF-3-immunoreactivity following MIA treatment was measured in L5 on days 8 and 14 (P < 0.05, Kruskal-Wallis and Mann-Whitney U-test), compared to saline controls. Furthermore, in an additional study animals were orally dosed vehicle (5 ml/kg), naproxen (0.3-10 mg/kg), celecoxib (1-10 mg/kg), amitriptyline (3-30 mg/kg) and gabapentin (10-100 mg/kg) and evaluated for weight-bearing asymmetry on days 14, 21 and 28 post-MIA. Significant resolution of weight-bearing was observed at high and intermediate doses of amitriptyline and gabapentin at all time points (P < 0.05, ANOVA, post-hoc Bonferroni's. vs pre-dose measurements). Transient and weak effects were observed with naproxen (10 mg/kg) on days 14 and 28, whereas celecoxib showed no significant effects. Collectively, these data suggest that this putative model of OA is associated with an early phase neuropathy in the L5 innervation territory of the knee. (c) 2007 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.