Puts Sofie, Njemini Rose, Bilterys Thomas, Lefeber Nina, Scheerlinck Thierry, Nijs Jo, Beckwée David, Bautmans Ivan
Gerontology Department, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
Frailty & Resilience in Ageing (FRIA) Research Unit, Vitality Research Group, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
J Clin Med. 2024 Sep 2;13(17):5212. doi: 10.3390/jcm13175212.
: To investigate if intra-articular biomarkers relate to peripheral and central sensitization in patients with late-stage knee osteoarthritis (KOA). : A total of 17 (6M, 11F) patients (aged 69 ± 10 years) were assessed for peripheral (pressure pain thresholds (PPT)) and central (temporal summation (TS) and conditioned pain modulation (CPM)) sensitization the day before total knee arthroplasty. Synovial fluid was collected during surgery and assayed for IL-6, IL-8, IL-10, TNF-α, CXCL-10, BDNF, NGF, CCL2, CCL5, VEGF, IL-1RI, MMP-1, MMP-7, IL-1β, and CXCL-9. Associations of biomarkers and their combinations reflecting chronic (CXCL-9) and acute ((CCL2×CXCL-10)/IL-10)) inflammation, cartilage degeneration (MMP-1×MMP-7), and neurotrophy (NGF×BDNF) with PPT, TS, and CPM were analyzed by bivariate correlations and by multiple linear regression analyses corrected for BMI, sex, and age. : The medial joint line and the superior medial joint region showed the lowest PPT. Higher acute inflammation related significantly to worse pressure tenderness at the superior medial joint region (R = 0.642; = 0.010). Cartilage degeneration and chronic inflammation were associated with both absolute (R = 0.827; = 0.001) and relative CPM (R = 0.882; < 0.001). Acute inflammation and neurotrophy were related to relative TS at the m. tibialis anterior (R = 0.728; = 0.02). : This study demonstrates that increased levels of intra-articular biomarkers of acute inflammation are related to peripheral sensitization and that biomarkers of cartilage degeneration and chronic inflammation are associated with central sensitization. These results may be a stepping-stone toward a better understanding of the working mechanism of peripheral and central sensitization in KOA pain and the development of more targeted therapeutic interventions.
研究晚期膝关节骨关节炎（KOA）患者关节内生物标志物是否与外周和中枢敏化相关。
对17例（6例男性，11例女性）患者（年龄69±10岁）在全膝关节置换术前一天进行外周（压痛阈值（PPT））和中枢（时间总和（TS）和条件性疼痛调制（CPM））敏化评估。手术期间收集滑液，检测白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、白细胞介素-10（IL-10）、肿瘤坏死因子-α（TNF-α）、CXC趋化因子配体10（CXCL-10）、脑源性神经营养因子（BDNF）、神经生长因子（NGF）、CC趋化因子配体2（CCL2）、CC趋化因子配体5（CCL5）、血管内皮生长因子（VEGF）、白细胞介素-1受体拮抗剂（IL-1RI）、基质金属蛋白酶-1（MMP-1）、基质金属蛋白酶-7（MMP-7）、白细胞介素-1β（IL-1β）和CXC趋化因子配体9（CXCL-9）。通过双变量相关性分析和校正体重指数（BMI）、性别和年龄的多元线性回归分析，分析反映慢性（CXCL-9）和急性（（CCL2×CXCL-10）/IL-10））炎症、软骨退变（MMP-1×MMP-7）和神经营养（NGF×BDNF）的生物标志物及其组合与PPT、TS和CPM的相关性。
内侧关节线和内侧关节上区的PPT最低。较高的急性炎症与内侧关节上区更严重的压痛显著相关（R = 0.642；P = 0.010）。软骨退变和慢性炎症与绝对CPM（R = 0.827；P = 0.001）和相对CPM均相关（R = 0.882；P < 0.001）。急性炎症和神经营养与胫骨前肌的相对TS相关（R = 0.728；P = 0.02）。
本研究表明，急性炎症关节内生物标志物水平升高与外周敏化相关，软骨退变和慢性炎症生物标志物与中枢敏化相关。这些结果可能是迈向更好理解KOA疼痛中外周和中枢敏化工作机制以及开发更具针对性治疗干预措施的垫脚石。
