Intra-articular tibiofemoral injection of a nonsteroidal anti-inflammatory drug has no detrimental effects on joint mechanics in a rat model

Abstract

Administration of intra-articular medications, including corticosteroids and analgesics, is common clinical practice for knee pathology and dysfunction. Non-steroidal anti-inflammatory drugs (NSAIDs) are another category of medication commonly prescribed for their analgesic and anti-inflammatory properties. Recent studies demonstrated the efficacy of injectable NSAIDs in the treatment of intra-articular pathology and postoperative analgesia. However, little data exist regarding the safety of intra-articular injection, despite the increase in its application. Therefore, we investigated the effects of intra-articular NSAID injection on articular cartilage, the anterior cruciate ligament (ACL), and joint function in the rat. Sixty-four Sprague-Dawley rats were divided into either saline (SAL) or ketorolac (NSAID) tibiofemoral single injection treatment groups. Animals were euthanized at 2, 7, 28, and 84 days post-injection for histological and mechanical analyses. Additionally, a subset of animals underwent longitudinal ambulatory evaluation to determine joint functional properties. We hypothesized that intra-articular ketorolac injection would result in no detrimental mechanical, histological, or functional changes. No differences were reported between the NSAID and SAL groups in any of the parameters measured at any time point, demonstrating the potential safety of intra-articular NSAID administration. Therefore, NSAID injection could be further considered for clinical application in humans.

Keywords: NSAID; injection; intra-articular; knee; mechanics.

Figure 1

Group numbers correspond to each time point (−1, 2, 7, 28, and 84 days) for both NSAID and SAL groups. Gait analysis (GA) measurements were taken at each time point. Histological and mechanical evaluations were performed on the articular cartilage and ACL.

Figure 2

ACL mechanical testing set-up. (A) ACL isolated between the tibia and femur embedded in PMMA. Stain lines were placed along the ligament for optical tracking. (B) Sagittal view of testing set-up with custom fixtures to hold at 45° knee flexion.

Figure 3

Ultrasound image of medial tibial plateau articular cartilage segmentation. (A) Sagittal and (B) coronal ultrasound images with markers defining the cartilage and bone surfaces. (C) Thickness map of cartilage with center region of interest defined.

Figure 4

Measurements from force plate and paw placement analysis showed no differences between NSAID and SAL groups. Changes over time were statistically significant in speed.

Figure 5

No differences in ACL mechanics between NSAID and SAL groups. Changes in time were statistically significant in max load, percent relaxation, max stress, and cross-sectional area.

Figure 6

Representative images of (A,B) ACL stained with H&E and (C,D) cartilage stained with Saf-O/FG. (A,C) Stitched images of the femur to demonstrate the regions for quantitative evaluation. (B,D) Representative 200× images for quantitative cellular evaluation.

Figure 7

(A) Equilibrium modulus of cartilage obtained from indentation testing and (B) cartilage thickness obtained from high-frequency ultrasound showed no differences between the NSAID and SAL groups. Changes over time were statistically significant.