膝骨关节炎(KOA)表现为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,这给KOA疼痛研究的建模方法选择带来了困难。
研究三种常用的KOA大鼠模型的感觉神经支配特征以及滑膜纤维化与痛觉过敏的相关性。
KOA模型是通过内侧半月板(DMM)的失稳诱导的,前交叉韧带横断(ACLT),和一碘乙酸酯(MIA),分别。机械,冷和热退出阈值(MWT,测量CWT和TWT)。收集的组织用于病理切片,免疫荧光和定量分析。
KOA滑膜显示更多I型胶原沉积,CD31、VEGF和TGF-β的表达增加。这些变化在手术模型中最为明显,DMM在第14天表现最突出,ACLT在第28天表现最突出。第14天,机械性痛觉过敏和冷性痛觉过敏的变化在DMM模型中最典型,并且在统计学上与MIA不同。Ⅰ型胶原百分比与MWT值呈负相关(r=-0.88),以及CWT值(r=-0.95)。DMM滑膜显示轴突染色较多,上调CGRP,TRPV1、NGF和Netrin1与MIA比拟。在第28天也观察到上述变化,但ACLT取代DMM作为最典型的。在DRG中,在第14天,只有CGRP和NGF的水平在KOA模型中有所不同,在DMM中最高,与MIA相比有统计学差异。
本研究描述了不同KOA模型大鼠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,手术建模尤其是ACLT方法更推荐用于KOA疼痛研究。
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.