Persistent synovial inflammation plays important roles in persistent pain development in the rat knee before cartilage degradation reaches the subchondral bone.
Persistent synovial inflammation plays important roles in persistent pain development in the rat knee before cartilage degradation reaches the subchondral bone.
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DOI：
10.1186/s12891-018-2221-5
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发表时间：
2018-08-16
影响因子：
2.3
通讯作者：
Muneta T
中科院分区：
文献类型：
--
作者：
Hoshino T;Tsuji K;Onuma H;Udo M;Ueki H;Akiyama M;Abula K;Katagiri H;Miyatake K;Watanabe T;Sekiya I;Koga H;Muneta T
膝骨关节炎（OA）的主要主诉是持续疼痛。与急性炎症性疼痛不同，持续性疼痛通常难以控制，因为其病理尚不完全清楚。为了阐明持续疼痛的潜在机制，我们通过向关节腔注射单碘乙酸（MIA）建立了2种不同的炎症性关节炎模型，并对大鼠关节炎模型中滑膜组织和关节软骨的结构变化、感觉神经元重排和疼痛回避行为进行了综合分析。雄性Wistar大鼠右膝关节内注射MIA （0.2 mg/30 μL，低剂量组；1 mg/30 μL，高剂量组），左膝关节内注射磷酸缓冲盐水（PBS, 30 μL，对照组）。采用逆行神经示踪剂氟金（FG）标记神经纤维，以识别支配背根神经节（DRG）关节的感觉神经元。献祭前5 - 7天，双膝在麻醉状态下关节内注射2% FG (5 μL) PBS。我们在第0、1、3、5、7、14、21和28天进行疼痛回避行为测试（失容和von Frey测试）。在第5、14、28天处死大鼠，切除膝关节和DRG进行组织学检查。膝关节用苏木精、伊红、红花素O、降钙素基因相关肽（CGRP）染色。用CGRP对DRG进行免疫染色。在低剂量MIA模型中观察到短暂的炎症反应，随后出现轻度关节软骨退变，而在高剂量模型中观察到滑膜组织持续炎症并发生结构改变（纤维化）。在高剂量模型中，注射mia后2周内观察到全层软骨退变。疼痛回避行为测试表明，在关节软骨退变到达软骨下骨之前，持续滑膜炎症和髌下脂肪垫的结构改变可能在持续膝关节疼痛中起重要作用。在关节软骨退化到达软骨下骨板之前，没有滑膜组织结构改变的短暂炎症不会引起大鼠膝关节的持续疼痛。本文的在线版本（10.1186/s12891-018-2221-5）包含补充材料，授权用户可使用。
The major complaint of knee osteoarthritis (OA) is persistent pain. Unlike acute inflammatory pain, persistent pain is usually difficult to manage since its pathology is not fully understood. To elucidate the underlying mechanisms of persistent pain, we established 2 different inflammation-induced arthritis models by injecting monoiodo-acetic acid (MIA) into the joint cavity and performed integrated analyses of the structural changes in the synovial tissue and articular cartilage, sensory neuron rearrangement, and pain avoidance behavior in a rat arthritis model. Male Wistar rats received intra-articular injections of MIA (0.2 mg/30 μL, low-dose group; 1 mg/30 μL, high-dose group) in the right knee and phosphate buffered saline (PBS; 30 μL, control group) in the left knee. Fluorogold (FG), a retrograde neural tracer, was used to label the nerve fibers for the identification of sensory neurons that dominate the joints in the dorsal root ganglion (DRG). Both knees were subjected to the intra-articular injection of 2% FG in PBS (5 μL) under anesthesia 5–7 days prior to sacrifice. We performed pain avoidance behavior tests (incapacitance and von Frey tests) at 0, 1, 3, 5, 7, 14, 21, and 28 days. At 5, 14, and 28 days, the rats were sacrificed and the knee joint and DRG were excised for histological assessment. The knee joints were stained with hematoxylin and eosin, safranin O, and calcitonin gene-related peptide (CGRP). The DRG were immunostained with CGRP. A transient inflammatory response followed by mild articular cartilage degeneration was observed in the low-dose MIA model versus persistent inflammation with structural changes in the synovial tissue (fibrosis) in the high-dose model. In the high-dose model, full-thickness cartilage degeneration was observed within 2 weeks post-MIA injection. The pain avoidance behavior tests indicated that persistent synovial inflammation and structural changes of the infrapatellar fat pad may play important roles in persistent knee joint pain before the articular cartilage degeneration reaches the subchondral bone. Transient inflammation without structural changes of the synovial tissues did not induce persistent pain in the rat knee joint before degradation of the articular cartilage reached the subchondral bone plate. The online version of this article (10.1186/s12891-018-2221-5) contains supplementary material, which is available to authorized users.
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影响因子：
7
作者：
Mapp, P. I.;Sagar, D. R.;Ashraf, S.;Burston, J. J.;Suri, S.;Chapman, V.;Walsh, D. A.
通讯作者：
Walsh, D. A.
影响因子：
--
作者：
Guingamp, C;GegoutPottie, P;Gillet, P
通讯作者：
Gillet, P
影响因子：
7
作者：
Moon, S-J;Woo, Y. -J.;Min, J. -K.
通讯作者：
Min, J. -K.
影响因子：
7.3
作者：
Mapp, Paul I.;McWilliams, Daniel F.;Walsh, David A.
通讯作者：
Walsh, David A.
影响因子：
2.3
作者：
Hunter, David J.;McDougall, Jason J.;Keefe, Francis J.
通讯作者：
Keefe, Francis J.