The Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Orthopedics, Nanjing 210029, China.
Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu 210029, China.
J Adv Res. 2021 Jun 15;35:141-151. doi: 10.1016/j.jare.2021.06.007. eCollection 2022 Jan.
Knee osteoarthritis (KOA) showed synovial fibrosis and hyperalgesia, although the correlation between the two is unclear. Besides, the specific changes of sensory innervation in animal models are still controversial, which makes it difficult to choose the modeling methods for KOA pain research.
Study the characteristics of sensory innervation within three commonly used KOA rat models and the correlation between synovial fibrosis and hyperalgesia.
KOA models were induced by destabilization of medial meniscus (DMM), anterior cruciate ligament transection (ACLT), and monoiodoacetate (MIA), respectively. Mechanical, cold and thermal withdrawal threshold (MWT, CWT and TWT) were measured. The harvested tissues were used for pathological sections, immunofluorescence and quantitative analysis.
KOA synovium showed more type I collagen deposition, increased expression of CD31, VEGF and TGF-β. These changes were most pronounced in surgical models, with DMM presenting the most prominent at Day 14 and ACLT at Day 28. Day 14, changes in mechanical hyperalgesia and cold hyperalgesia were most typical in DMM model and statistically different from MIA. There was a negative correlation between the percentage of type I collagen and MWT value (r = -0.88), as well as CWT value (r = -0.95). DMM synovium showed more axonal staining, upregulated CGRP, TRPV1, NGF and Netrin1 compared with MIA. Above changes were also observed at Day 28, but ACLT replaced DMM as the most typical. In DRG, only the levels of CGRP and NGF were different among KOA models at Day 14, and the highest in DMM, which was statistically different compared with MIA.
This study described the details of sensory innervation in different KOA model of rats, and the degree of synovial fibrosis was positively correlated with the pain sensitivity of KOA model rats. Additionally, surgical modeling especially ACLT method is more recommended for KOA pain research.
膝骨关节炎（KOA）表现出滑膜纤维化和痛觉过敏，尽管两者之间的相关性尚不清楚。此外，动物模型中感觉神经支配的具体变化仍存在争议，这使得难以选择 KOA 疼痛研究的建模方法。
研究三种常用 KOA 大鼠模型中感觉神经支配的特征及其与滑膜纤维化和痛觉过敏的相关性。
分别通过内侧半月板不稳定（DMM）、前交叉韧带切断（ACLT）和单碘乙酸（MIA）诱导 KOA 模型。测量机械、冷和热退缩阈值（MWT、CWT 和 TWT）。采集组织进行病理切片、免疫荧光和定量分析。
KOA 滑膜中 I 型胶原沉积增加，CD31、VEGF 和 TGF-β表达增加。这些变化在手术模型中最为明显，DMM 在第 14 天和 ACLT 在第 28 天最为显著。第 14 天，DMM 模型中机械性痛觉过敏和冷痛觉过敏的变化最为典型，与 MIA 相比具有统计学差异。I 型胶原百分比与 MWT 值（r=-0.88）和 CWT 值（r=-0.95）呈负相关。与 MIA 相比，DMM 滑膜中轴突染色增加，CGRP、TRPV1、NGF 和 Netrin1 上调。这些变化在第 28 天也观察到，但 ACLT 取代 DMM 成为最典型的。在 DRG 中，只有在第 14 天 KOA 模型之间 CGRP 和 NGF 的水平不同，DMM 最高，与 MIA 相比具有统计学差异。
本研究描述了不同 KOA 大鼠模型中感觉神经支配的细节，滑膜纤维化程度与 KOA 模型大鼠的疼痛敏感性呈正相关。此外，手术建模特别是 ACLT 方法更推荐用于 KOA 疼痛研究。
