Characterization and comparison of rat monosodium iodoacetate and medial meniscal tear models of osteoarthritic pain
Characterization and comparison of rat monosodium iodoacetate and medial meniscal tear models of osteoarthritic pain
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DOI：
10.1002/jor.23869
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发表时间：
2018-08-01
影响因子：
2.8
通讯作者：
McGaraughty, Steve
中科院分区：
文献类型：
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作者：
Brederson, Jill-Desiree;Chu, Katharine L.;McGaraughty, Steve
骨关节炎(OA)是一种退行性关节炎，可导致关节功能丧失和慢性疼痛。由骨性关节炎引起的病理性疼痛状态涉及外周和中枢神经系统的可塑性改变，然而，骨性关节炎的细胞机制尚不完全清楚。我们研究了内侧半月板撕裂(MMT)手术模型和关节腔内注射碘乙酸单钠(MIA)化学药物建立的大鼠骨关节炎模型。这两种模型在膝关节和相关骨骼中都产生了与OA病理一致的组织学变化。两种模型均增加了L3的p38活性，但不增加L4背根神经节(DRG)的p38活性，增加了L3 DRG的酪氨酸羟化酶免疫染色(表明交感神经发芽)，并增加了丘脑神经元的磷酸化(P)CREB。MIA-OA组大鼠脊髓p38和PERK表达增强，前额叶皮质pCREB表达增强，而MMT-OA组大鼠脊髓p38和PERK表达增强。利用体内电生理学，两种模型都发现大动态范围神经元的自发活动和对刺激膝关节的反应增强。然而，在MIA-OA大鼠中观察到了更广泛的敏化，MIA-OA大鼠具有爪状感受区的神经元自发放电的速度高于MMT-OA大鼠。综上所述，MIA和MMT的OA模型有几个与主要躯体感觉通路的组织病理学和敏化相关的共同特征，但是，观察到的模型之间的差异突出了相关特定损伤的独特后果，当选择OA模型和解释数据结果时，这些差异应该被考虑在内。(C)2018年骨科研究会。由Wiley期刊公司出版，J Orthop Res 36：2109-2117,2018。
Osteoarthritis (OA) is a degenerative form of arthritis that can result in loss of joint function and chronic pain. The pathological pain state that develops with OA disease involves plastic changes in the peripheral and central nervous systems, however, the cellular mechanisms underlying OA are not fully understood. We characterized the medial meniscal tear (MMT) surgical model and the intra-articular injection of monosodium iodoacetate (MIA) chemical model of OA in rats. Both models produced histological changes in the knee joint and associated bones consistent with OA pathology. Both models also increased p38 activation in the L3, but not L4 dorsal root ganglia (DRG), increased tyrosine hydroxylase immunostaining in the L3 DRG indicating sympathetic sprouting, and increased phosphorylated (p)CREB in thalamic neurons. In MIA-OA, but not MMT-OA rats, p38 and pERK were increased in the spinal cord, and pCREB was enhanced in the prefrontal cortex. Using in vivo electrophysiology, elevated spontaneous activity and increased responsiveness of wide dynamic range neurons to stimulation of the knee was found in both models. However, a more widespread sensitization was observed in the MIA-OA rats as neurons with paw receptive fields spontaneously fired at a greater rate in MIA-OA than MMT-OA rats. Taken together, the MIA and MMT models of OA share several common features associated with histopathology and sensitization of primary somatosensory pathways, but, observed differences between the models highlights unique consequences of the related specific injuries, and these differences should be considered when choosing an OA model and when interpreting data outcomes. (c) 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2109-2117, 2018.