Potential causal role of synovial complement system activation in the development of post-traumatic osteoarthritis after anterior cruciate ligament injury or meniscus tear.

Anterior cruciate ligament (ACL) injury and meniscal tear (MT) are major causal factors for developing post-traumatic osteoarthritis (PTOA), but the biological mechanism(s) are uncertain. After these structural damages, the synovium could be affected by complement activation that normally occurs in response to tissue injury. We explored the presence of complement proteins, activation products, and immune cells, in discarded surgical synovial tissue (DSST) collected during arthroscopic ACL reconstructive surgery, MT-related meniscectomy and from patients with OA. Multiplexed immunohistochemistry (MIHC) was used to determine the presence of complement proteins, receptors and immune cells from ACL, MT, OA synovial tissue vs. uninjured controls. Examination of synovium from uninjured control tissues did not reveal the presence of complement or immune cells. However, DSST from patients undergoing ACL and MT repair demonstrated increases in both features. In ACL DSST, a significantly higher percentage of C4d+, CFH+, CFHR4+ and C5b-9+ synovial cells were present compared with MT DSST, but no major differences were seen between ACL and OA DSST. Increased cells expressing C3aR1 and C5aR1, and a significant increase in mast cells and macrophages, were found in ACL as compared to MT synovium. Conversely, the percentage of monocytes was increased in the MT synovium. Our data demonstrate that complement is activated in the synovium and is associated with immune cell infiltration, with a more pronounced effect following ACL as compared to MT injury. Complement activation, associated with an increase in mast cells and macrophages after ACL injury and/or MT, may contribute to the development of PTOA.

Association Between the 2011 Fibromyalgia Survey Criteria and Multisite Pain Sensitivity in Knee Osteoarthritis.

OBJECTIVES: The present study evaluated the relationship between the 2011 American College of Rheumatology fibromyalgia (FM) survey criteria and quantitative sensory testing (QST). MATERIALS AND METHODS: Patients with knee osteoarthritis scheduled to undergo knee arthroplasty completed the FM survey criteria and self-report measures assessing clinical symptoms. Patients also underwent a battery of QST procedures at the surgical knee and remote body sites, including pressure algometry, conditioned pain modulation, and temporal summation. All assessments were completed before surgery. FM survey criteria were used to calculate a continuous FM score indicating FM severity. RESULTS: A total of 129 patients were analyzed. Of these, 52.7% were female, 93.8% were Caucasian, and 3.8% met the FM survey criteria for FM classification. Mean age for females (63.6 y) and males (64.7 y) was similar. Females and males differed significantly in nearly every outcome, including FM severity, clinical pain, anxiety, depression, and pressure pain sensitivity. In females, FM scores significantly correlated with pressure pain sensitivity, but not conditioned pain modulation or temporal summation, such that increased sensitivity was associated with greater FM severity at all body sites examined. In addition, as FM scores increased, the association between pain sensitivity at the surgical knee and pain sensitivity at remote body sites also increased. No relationship between FM score and QST was observed in males. DISCUSSION: We demonstrated an association between diffuse hyperalgesia as measured by QST and FM severity in females with knee osteoarthritis. These results suggest that the FM survey criteria may represent a marker of pain centralization in females with potential utility in clinical decision making.