Nociceptin, an endogenous neuropeptide with similar structure to classical opioids, is involved in a variety of systemic modulatory responses. Osteoarthritis, a chronic neuroinflammatory condition, appears to have both pro- and anti-inflammatory processes that are possibly linked to nociceptin. The presence of nociceptin in human synovial fluid has been documented in some studies; however, in others it was not detected. The goal of this pilot study was to determine whether nociceptin was present in the synovial fluid of osteoarthritic knees.
Patients undergoing primary total knee arthroplasty were enrolled after Institutional Review Board approval was obtained. Synovial fluid was aspirated from patients’ operative knee joints and blood samples were obtained. A commercially available enzyme Immunoassay kit was used to test for nociceptin. A linear mixed-effects model was developed to account for the repeated measurements and baseline covariates. Least squares (adjusted) means were derived from the model to compare the sample types and to compare subgroups.
Twenty patients were included in this study. Nociceptin was detected in the synovial fluid and plasma of all patients. The mean concentration (± standard deviation) of nociceptin in synovial fluid was 28.7 ± 18.2 pg/ml. The mean concentration of nociceptin in plasma were 45.2 ± 24.3 pg/ml pre-procedure, and 40.1 ± 20.6 pg/ml post-tourniquet deflation. The nociceptin concentration in synovial fluid was significantly lower than the nociceptin concentration in plasma, both pre-procedure and post-tourniquet deflation (p=0.002 and p=0.016 respectively). The nociceptin concentration in both plasma and synovial fluid was significantly lower in females versus males (p=0.012).
We demonstrated that nociceptin is present in synovial fluid and plasma of patients undergoing total knee arthroplasty. This implies a potential role for nociceptin in modulating inflammation in osteoarthritis.
ClinicalTrials.gov, NCT02528916. Retrospectively registered on 19 August 2015, https://clinicaltrials.gov/ct2/show/NCT02528916