Nasonova Research Institute of Rheumatology, Moscow, Russia
Elena Tchetina is a Leading Scientist, Principle Investigator, Immunology & Molecular Biology Department, of NASONOVA RESEARCH INSTITUTE OF RHEUMATOLOGY, at Moscow, Russia since Oct.2006- until present. She studies genetics, cellular, and molecular physiology of osteoarthritis, rheumatoid arthritis, and osteoporosis. The importance of metabolic signalling pathways for the disease progression, inflammation, pain perception, joint destruction, and the response to therapy has been investigated in osteoarthritic, rheumatoid arthritis, and osteoporotic patients.
Previously, from Nov.1996 until Sept.2006, she worked at McGILL UNIVERSITY, at Montreal, Canada at Shriners Hospitals for Children, at the Joint Diseases Laboratory, as Research Associate and conducted research in molecular cell biology, connective tissue physiology and bone development: She studied the mechanisms of the onset of cartilage degradation in osteoarthritis (OA) at gene expression and protein level.
Statement of the Problem: Osteoarthritis (OA) is a major source of pain, disability, and socioeconomic expenditures worldwide. Severe 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. Therefore, identification of the causes that affect the outcome of arthroplasty would permit a more accurate selection of patients, provide them with more accurate anticipations, and augment the profits of surgery for each individual. In addition, there is a need to predict the results of surgical intervention in terms of maintaining postoperative pain due to the high cost of arthroplasty.
Methodology and Theoretical Orientation: Here we assessed the importance of clinical indices, pain-related protease and proinflammatory cytokine gene expressions in the peripheral blood for prediction of postoperative pain (POP) development in patients with end-stage knee or hip osteoarthritis (OA) prior to arthroplasty. We examined peripheral blood of 31 hip and 50 knee OA patients undergoing joint replacement surgery and 26 healthy volunteers. Patients were tested before and 6 months after surgery. Pain was assessed prior to surgery using VAS index and neuropathic pain questionnaires DN4 and PainDETECT. Functional activity was evaluated by WOMAC. After surgery pain indices according to VAS of 30% and higher were considered. Total RNA isolated from whole blood was used in expression studies for cathepsin S, interleukin (IL)-1β, tumor necrosis factor (TNF)α, and cyclooxygenase (COX)2 genes using quantitative real-time RT-PCR.
Findings: After 6 months’ post-surgery pain complaints were obtained from 38.7% patients with hip OA and 34% patients with knee OA. Prior to surgery expression of cathepsin S, IL- 1β, TNFα, and COX2 genes was significantly upregulated in all examined subsets of OA patients compared with healthy controls. Patients with knee and hip OA who developed POP demonstrated significantly higher cathepsin S gene expression compared with painless subjects prior to surgery. In addition, patients with knee OA who developed POP demonstrated significantly higher expression of IL-1β and TNFα compared with painless subjects while no significant differences in the expression of proinflammatory cytokines were observed in both subsets of patients with hip OA.
Conclusion & Significance: Cathepsin S gene expression measured in the peripheral blood prior to surgery might serve as a prognostic biomarker of postoperative pain development in patients with knee and hip OA. Differences in prognostic value of IL-1β and TNFα gene expression measured in the peripheral blood prior to surgery might indicate that destruction of the hip and knee in OA is caused by different pathophysiological mechanisms. This study was funded by Russian Ministry of Education and Science (Project no. 1021062512064-0).