BACKGROUND Inflammatory mediators in the synovial fluid (SF) play critical roles in the initiation and development of pain in knee osteoarthritis (KOA). However, data for inflammatory marker expression are conflicting, and the role of SF inflammatory mediators in neuropathic pain is not clear. Therefore, the aim of this study was to identify SF inflammatory mediators associated with nociceptive and neuropathic pain in KOA. METHODS Levels of IL-1β, IL-6, TNF-α, macrophage colony-stimulating factor, MMP-3, MMP-13, metalloproteinase with thrombospondin motifs 5, calcitonin gene-related peptide, neuropeptide Y, substance P and bradykinin were measured using enzyme-linked immunosorbent assays in 86 patients. Nociceptive pain was assessed using the numeric rating scale (NRS), visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score. Neuropathic pain was determined using the PainDETECT questionnaire. Moreover, knee function was evaluated by the WOMAC score and range of motion (ROM) assessments. Radiological grade was defined using the Kellgren-Lawrence (K-L) grading scale. RESULTS Pain scores measured using different methods correlated highly with each other. A worse K-L grade and knee function were associated with worse pain. Expression of IL-1β and IL-6 was increased in the early stage compared with the late stage. The NRS score correlated positively with age, K-L grade, and the WOMAC score and negatively with ROM and TNF-α expression. The VAS correlated positively with age, K-L grade, and the WOMAC score but negatively with ROM and levels of IL-1β, IL-6 and TNF-α. The WOMAC pain score did not correlate with any of the inflammatory mediators measured; it correlated only with ROM. The PainDETECT score correlated only with the WOMAC score. Expression of other inflammatory mediators did not correlate with any of the pain scores. CONCLUSIONS IL-1β, IL-6 and TNF-α play critical roles in pain in the early stage of KOA and correlate with pain. The catabolic enzymes and neuropeptides measured do not correlate with nociceptive and neuropathic pain. New biomarkers related to pain in the late stage need to be further investigated.

中文翻译：

---

与膝骨关节炎疼痛相关的滑液中炎性介质的分布图。

背景技术滑液（SF）中的炎性介质在膝骨关节炎（KOA）的疼痛的发生和发展中起关键作用。但是，有关炎症标志物表达的数据相互矛盾，并且尚不清楚SF炎症介质在神经性疼痛中的作用。因此，本研究的目的是确定与KOA的伤害性和神经性疼痛相关的SF炎性介质。方法测定血浆中IL-1β，IL-6，TNF-α，巨噬细胞集落刺激因子，MMP-3，MMP-13，血小板反应蛋白基序5，降钙素基因相关肽，神经肽Y，P物质和缓激肽的水平。使用酶联免疫吸附测定法治疗86例患者。使用数字评分量表（NRS）评估伤害性疼痛，视觉模拟量表（VAS）和西安大略和麦克马斯特大学骨关节炎指数（WOMAC）疼痛评分。使用PainDETECT问卷确定神经性疼痛。此外，通过WOMAC评分和运动范围（ROM）评估来评估膝盖功能。放射学等级是使用Kellgren-Lawrence（KL）等级量表定义的。结果使用不同方法测得的疼痛评分彼此高度相关。KL级和膝盖功能恶化与疼痛加剧有关。与晚期相比，IL-1β和IL-6的表达在早期增加。NRS评分与年龄，KL评分和WOMAC评分呈正相关，与ROM和TNF-α表达呈负相关。VAS与年龄，KL等级和WOMAC评分呈正相关，而与ROM和IL-1β水平呈负相关，IL-6和TNF-α。WOMAC疼痛评分与所测量的任何炎症介质均不相关。它仅与ROM相关。PainDETECT评分仅与WOMAC评分相关。其他炎症介质的表达与任何疼痛评分均不相关。结论IL-1β，IL-6和TNF-α在KOA早期对疼痛起关键作用，并与疼痛相关。测得的分解代谢酶和神经肽与伤害性和神经性疼痛无关。与晚期疼痛有关的新生物标志物需要进一步研究。结论IL-1β，IL-6和TNF-α在KOA早期对疼痛起关键作用，并与疼痛相关。测得的分解代谢酶和神经肽与伤害性和神经性疼痛无关。与晚期疼痛有关的新生物标志物需要进一步研究。结论IL-1β，IL-6和TNF-α在KOA早期对疼痛起关键作用，并与疼痛相关。测得的分解代谢酶和神经肽与伤害性和神经性疼痛无关。与晚期疼痛有关的新生物标志物需要进一步研究。