The effects of intra-articular injection of ibuprofen on knee joint cartilage and synovium in rats

Abstract

Objective: The aim of this animal study was to investigate the short and long-term local histomorphologic effects and the utility of intra-articular application of ibuprofen.

Methods: Forty-six Wistar Albino rats were used in the study. The rats were randomized into 5 groups of 8 and a sham group of 6. The 40 rats in the study groups were anaesthetised with 60 mg/kg of ketamine, then 0.25 ml ibuprofen (25 mg) was injected to the right knee joint of each rat (ibuprofen group) and 0.25 ml 0.9% saline to the left knee joint as the control group. To the 6 rats in the sham group, only puncture was applied to both knee joints. The rats in each of the 5 study groups were sacrificed on days 1, 2, 7, 14 and 21 respectively. The histomorphologic changes were graded on a 6-point scale regarding inflammation of the synovia, cartilage tissue, and subchondral bone. Inflammation scores were compared using the Mann Whitney U-test and comparisons of the sacrifice day and drug used were evaluated with the Kruskal Wallis test. The p values below 0.05 were considered as significant.

Results: Statistically significant difference was found between the ibuprofen injected knees (10/40) and the saline injected (0/40) and sham knees (0/12) in respect of hematoma positivity (p = 0.002). Significantly higher inflammation scores were found in ibuprofen injected knees on the 1st, 2nd, 7th and 14th days compared to controls and sham (p < 0.05). Inflammation scores were similar in ibuprofen injected knees with and without hematoma (p > 0.05). Inflammation of the ibuprofen injected group was most severe on day one and the severity of inflammation reduced gradually throughout the 3 weeks.

Conclusion: Our results show that intra-articular injection of ibuprofen can cause intra-articular hematoma. It also leads to transient inflammation of the synovia that is more severe in the early period, which gradually recovers.

Keywords: Cartilage; Ibuprofen; Intra-articular; Knee; Synovium.

Fig. 1

Light microscopic views of rat knee joint. Haematoxylin-eosinn × 100. A: Degree 0 from group SR2; normal histological appearance. B: Degree 1 from group D4; minimal inflammation, mild congestion. C: Degree 2 from group D2; moderate inflammation, lymphocyte infiltration. D: Degree 3 from group D1; severe inflammation o,edema. E: Degree 4 from group D1; very severe inflammation.

Fig. 2

D1: 1st daysacrificedd group that was injected ibuprofen in the right knee. D2: 2nd daysacrificedd group that was injected ibuprofen in the right knee. D7: 7th daysacrificedd group that was injected ibuprofen in the right knee. D14: 14th daysacrificedd group that was injected ibuprofen in the right knee. D21: 21st daysacrificedd group that was injected ibuprofen in the right knee. *p < 0.05 compared to saline and sham, Ʊ p < 0.05 ibuprofen group compared to day 1, #p < 0.05 compared to day.