Background/Purpose: 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. Here we aimed to identify genes whose expression in the peripheral blood prior to surgery would indicate OA patients under risk of post-operative pain development.

Methods: We examined peripheral blood of 26 healthy volunteers (55±8.3 years) and 40 end-stage OA patients (56.5±8.9 years) undergoing knee joint replacement surgery. Patients were examined prior to surgery and 6 months’ post-surgery. Nociceptive pain was assessed using VAS index whereas neuropathic pain, using DN4 and PainDETECT questionnaires prior to surgery. Functional activity was evaluated by WOMAC. Pain indices after surgery 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 prior to surgery.

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 and those subjects who did not develop pain after surgery compared to healthy controls. However, no difference in the clinical levels of the pain-related and functional indices in the examined patients was observed 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, 10.11 for caspase 3, 10.09 for cathepsin K. Among the examined genes cathepsin S expression was the most appropriate predictor of post-operative 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.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/cathepsin-s-gene-expression-measured-in-the-peripheral-blood-of-osteoarthritic-patients-prior-to-surgery-as-a-biomarker-of-post-operative-pain-development/