Tchetina Elena V, Glemba Kseniya E, Markova Galina A, Naryshkin Evgeniy A, Taskina Elena A, Makarov Maksim A, Lila Aleksandr M
Immunology and Molecular Biology Department, Nasonova Research Institute of Rheumatology, 115522 Moscow, Russia.
Surgery Department, Nasonova Research Institute of Rheumatology, 115522 Moscow, Russia.
Life (Basel). 2020 Sep 30;10(10):224. doi: 10.3390/life10100224.
Osteoarthritis (OA) pain implies an indication for joint replacement in patients with end-stage OA. However, chronic postoperative pain is observed in 10-40% of patients with OA. Here, we identified genes whose expression in the peripheral blood before surgery could denote the risk of postoperative pain development. We examined the peripheral blood of 26 healthy subjects and 50 patients with end-stage OA prior to joint replacement surgery. Pain was evaluated before surgery using the visual analog scale (VAS) index and neuropathic pain questionnaires, Douleur Neuropathique 4 Questions (DN4) and PainDETECT questionnaires. Functional activity was assessed using the Western Ontario and McMaster Universities osteoarthritis index (WOMAC). Three and six months after surgery, pain indices according to VAS of 30% and higher were considered. Metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)1 protein levels were measured using ELISA in the peripheral blood mononuclear cells (PBMCs). Total RNA isolated from whole blood was analysed using quantitative real-time RT-PCR for caspase-3, MMP-9, TIMP1, cathepsins K and S, tumour necrosis factor (TNF)α, interleukin (IL)-1β, and cyclooxygenase (COX)-2 gene expression. Seventeen patients reported post-surgical pain. Expression of cathepsins K and S, caspase-3, TIMP1, IL-1β, and TNFα genes before surgery was significantly higher in these patients compared to pain-free patients with OA. Receiver-operating characteristic (ROC) curve analyses confirmed significant associations between these gene expressions and the likelihood of pain development after arthroplasty. High baseline expression of genes associated with extracellular matrix destruction (cathepsins S and K, TIMP1), inflammation (IL-1β, TNFα), and apoptosis (caspase-3) measured in the peripheral blood of patients with end-stage OA before knee arthroplasty might serve as an important biomarker of postoperative pain development.
骨关节炎（OA）疼痛意味着终末期OA患者需要进行关节置换。然而，10%-40%的OA患者术后会出现慢性疼痛。在此，我们鉴定出了一些基因，其术前在外周血中的表达可预示术后疼痛发生的风险。我们检测了26名健康受试者和50名终末期OA患者在关节置换手术前的外周血。术前使用视觉模拟量表（VAS）指数以及神经病理性疼痛问卷、神经病理性疼痛4项问题（DN4）问卷和疼痛检测问卷对疼痛进行评估。使用西安大略和麦克马斯特大学骨关节炎指数（WOMAC）评估功能活动。术后3个月和6个月，考虑VAS评分30%及以上的疼痛指数。使用酶联免疫吸附测定法（ELISA）检测外周血单个核细胞（PBMC）中的金属蛋白酶（MMP）-9和金属蛋白酶组织抑制剂（TIMP）1蛋白水平。使用定量实时逆转录聚合酶链反应（RT-PCR）分析从全血中分离的总RNA，检测半胱天冬酶-3、MMP-9、TIMP1、组织蛋白酶K和S、肿瘤坏死因子（TNF）α、白细胞介素（IL）-1β和环氧化酶（COX）-2基因的表达。17名患者报告了术后疼痛。与无疼痛的OA患者相比，这些患者术前组织蛋白酶K和S、半胱天冬酶-3、TIMP1、IL-1β和TNFα基因的表达显著更高。受试者操作特征（ROC）曲线分析证实了这些基因表达与关节置换术后疼痛发生可能性之间存在显著关联。在终末期OA患者膝关节置换术前外周血中检测到的与细胞外基质破坏（组织蛋白酶S和K、TIMP1）、炎症（IL-1β、TNFα）和细胞凋亡（半胱天冬酶-3）相关的基因高基线表达，可能是术后疼痛发生的重要生物标志物。
