Development of Postoperative Pain in Patients with End-Stage Knee Osteoarthritis Is Associated with Upregulation of Genes Related to Extracellular Matrix Degradation, Inflammation, and Apoptosis Measured in the Peripheral Blood before Knee Surgery

Abstract

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.

Keywords

• knee osteoarthritis
• postoperative pain prediction
• gene expression
• peripheral blood