Thu0472 cathepsin S Gene Expression Measured in the Peripheral Blood of Osteoarthritic Patients Prior to Surgery as a Biomarker of Post-Operative Pain Development

Abstract

Background:Osteoarthritis (OA) is a chronic rheumatic disease, which involves pain, limited inflammation, and local destruction of the knee joint. OA pain is a major clinical symptom, which limits working capacity and denotes an important indication for joint replacement in the end-stage OA. In spite of significant number of positive outcomes, chronic postoperative pain represents a major adverse consequence of surgery, which is observed in 10-40% of OA patients. Therefore, identification of patients potentially capable of developing chronic postoperative pain prior to surgery could significantly improve therapy outcome. Recently we hypothesized that genes related to pain sensitization whose expression is upregulated in about 10-40% of the examined end-stage OA patient cohort might be responsible for postoperative pain. Retrospective analysis of gene expression in the peripheral blood of end-stage OA patients before joint replacement surgery revealed that expression of cathepsins S and K, caspase 3, and MMP-9 genes might be associated with postoperative pain development [Ann Rheum Dis,78, suppl 2:A520].Objectives:To examine the validity of our hypothesis in the prospective study.Methods:We examined peripheral blood of 26 healthy volunteers (average age 55±8.3 years old) and 40 end-stage OA patients (average age 56.5±8.9 years old) undergoing joint replacement surgery. Patients were examined 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. MMP-9 and caspase 3 protein levels were quantified by ELISA. Total RNA isolated from whole blood was used in expression studies for caspase 3; metalloproteinase (MMP)-9; cathepsins K and S genes. These were performed with quantitative real-time RT-PCR.Results:Out of 40 patients pain complaints were obtained from 9 patients (22,5%) after 6 months’ post-surgery. Prior to surgery all the examined genes were significantly upregulated in the patients who developed post-operative pain compared to healthy controls and those subjects who did not develop pain after surgery. However, no difference in the levels of the examined pain-related and functional indices in patients, who developed pain or not, was noted before surgery. ROC curve analyses confirmed significant associations (p<0.05) between expressions of the examined genes prior to surgery with the likelihood of pain development after surgery. The cut-off values for the examined gene expressions were 11.34 for cathepsin S (sensitivity of 0.89 and specificity of 0.76), 10.11 for caspase 3 (sensitivity of 0.86 and specificity of 0.65), 10.09 for cathepsin K (sensitivity of 0.86 and specificity of 0.78). Moreover, among the examined genes cathepsin S expression was the most informative predictor of postoperative pain development [AUC= 0.857, 95%CI (0.708-1.000)].Conclusion:High cathepsin S gene expression in the peripheral blood of the end-stage OA patients measured prior to joint replacement surgery could serve an important biomarker of post-operative pain development.Disclosure of Interests: :None declared