Pain Centre Versus Arthritis and NIHR Nottingham Biomedical Research Centre, School of Life Sciences, University of Nottingham, Nottingham, UK.
Centre for Analytical Bioscience, Advanced Materials and Healthcare Technologies Division, School of Pharmacy, University of Nottingham, Nottingham, UK.
Eur J Pain. 2022 Nov;26(10):2213-2226. doi: 10.1002/ejp.2036. Epub 2022 Sep 19.
Synovial inflammation has known contributions to chronic osteoarthritis (OA) pain, but the potential role in transitions from early to late stages of OA pain is unclear.
The slowly progressing surgical destabilization of the medial meniscus (DMM) murine OA model and sham control, was used in male C57BL/6J mice to investigate the interplay between knee inflammation, plasma pro- and anti-inflammatory oxylipins and pain responses during OA progression. Changes in joint histology, macrophage infiltration, chemokine receptor CX3CR1 expression, weight bearing asymmetry, and paw withdrawal thresholds were quantified 4, 8 and 16 weeks after surgery. Plasma levels of multiple bioactive lipid mediators were quantified using liquid chromatography with tandem mass-spectrometry (LC-MS/MS).
Structural joint damage was evident at 8 weeks post-DMM surgery onwards. At 16 weeks post-DMM surgery, synovial scores, numbers of CD68 and CD206 positive macrophages and pain responses were significantly increased. Plasma levels of oxylipins were negatively correlated with joint damage and synovitis scores at 4 and 8 weeks post-DMM surgery. Higher circulating levels of the pro-resolving oxylipin pre-cursor 17-HDHA were associated with lower weight bearing asymmetry at week 16.
The transition to chronic OA pathology and pain is likely influenced by both joint inflammation and plasma oxylipin mediators of inflammation and levels of pro-resolution molecules.
Using a slow progressing surgical model of osteoarthritis we show how the changing balance between local and systemic inflammation may be of importance in the progression of pain behaviours during the transition to chronic osteoarthritis pain.
滑膜炎症已知对慢性骨关节炎（OA）疼痛有贡献，但在 OA 疼痛从早期向晚期转变中的潜在作用尚不清楚。
使用内侧半月板（DMM）手术不稳的缓慢进展型 OA 小鼠模型和假手术对照，研究膝关节炎症、血浆促炎和抗炎氧化脂质与 OA 进展过程中疼痛反应之间的相互作用。手术后 4、8 和 16 周时，定量检测关节组织学变化、巨噬细胞浸润、趋化因子受体 CX3CR1 表达、体重偏差和足退缩阈值。使用液相色谱-串联质谱（LC-MS/MS）定量检测多种生物活性脂质介质的血浆水平。
DMM 手术后 8 周即可观察到结构关节损伤。DMM 手术后 16 周，滑膜评分、CD68 和 CD206 阳性巨噬细胞数量和疼痛反应显著增加。DMM 手术后 4 和 8 周，血浆氧化脂质水平与关节损伤和滑膜炎评分呈负相关。循环中促修复氧化脂质前体 17-HDHA 水平较高与 16 周时的体重偏差较低相关。
慢性 OA 病理和疼痛的转变可能受到关节炎症和炎症氧化脂质介质以及促修复分子的循环水平的影响。
我们使用一种缓慢进展的 OA 手术模型，显示了局部和全身炎症之间不断变化的平衡在向慢性 OA 疼痛转变过程中疼痛行为进展中的重要性。
