Early Anti-Inflammatory Effect of Bupivacaine−Meloxicam Therapy in a Rabbit Model of Arthrofibrosis

Abstract

Arthrofibrosis is a common complication following total knee arthroplasty and is the result of a dysregulated immuno-inflammatory cascade, which culminates in excessive scar deposition by myofibroblasts within the knee joint. Pharmacotherapies for arthrofibrosis are limited, with treatment reliant on manipulation under anesthesia or lysis of adhesions with or without component revision. Bupivacaine (a local anesthetic) and meloxicam (a nonsteroidal anti-inflammatory drug) combination therapy may exert antifibrotic properties by limiting inflammatory cell recruitment and the subsequent release of profibrotic cytokines. The purpose of this study was to evaluate the effects of this combination therapy in a rabbit model of arthrofibrosis by evaluating live and postsacrifice knee biomechanics and gene expression of posterior knee capsule tissue. Forty New Zealand white rabbits were equally divided into two experimental groups and prospectively studied to assess knee passive extension angles (PEA), terminal posterior capsular stiffness, and the inflammatory milieu of the posterior knee joint capsule. Experimental limbs with and without combination therapy showed similar live PEAs and terminal posterior capsular stiffness, with no significant differences between the groups. Gene expression analysis, however, revealed significant reduction in inflammatory genes but not profibrotic genes. In summary, bupivacaine and meloxicam combination therapy did not exert antifibrotic effects in a rabbit model of arthrofibrosis but significantly reduced the expression of inflammatory markers in the local environment of the posterior capsule.

Impact Statement

Arthrofibrosis after total knee arthroplasty remains a difficult complication without reliable pharmacologic prevention. In a rabbit model, single-dose intra-articular bupivacaine and meloxicam did not reduce fibrosis or joint stiffness but did significantly decrease expression of inflammatory genes. Clinically, this suggests that current perioperative formulations may be valuable for short-term pain and inflammation control but are unlikely to prevent arthrofibrosis. These findings underscore the need for alternative or sustained-delivery strategies to address this challenging complication in patients undergoing knee arthroplasty.