Do Different Cyclooxygenase Inhibitors Impair Rotator Cuff Healing in a Rabbit Model?

Abstract

Background:The effect of selective and non-selective cyclooxygenase (COX) inhibitors on tendon healing was variable. The purpose of the study was to evaluate the influence of non-selective COX inhibitor, ibuprofen and flurbiprofen axetil and selective COX-2 inhibitor, celecoxib on the tendon healing process in a rabbit model.Methods:Ninety-six New Zealand rabbits were used as rotator cuff repair models. After surgery, they were divided randomly into four groups: Ibuprofen (10 mg·kg−1·d−1), celecoxib (8 mg·kg−1·d−1), flurbiprofen axetil (2 mg·kg−1·d−1), and control group (blank group). All drugs were provided for 7 days. Rabbits in each group were sacrificed at 3, 6, and 12 weeks after tendon repair. Tendon biomechanical load failure tests were performed. The percentage of type I collagen on the bone tendon insertion was calculated by Picric acid Sirius red staining and image analysis. All data were compared among the four groups at the same time point. All data in each group were also compared across the different time points. Qualitative histological evaluation of the bone tendon insertion was also performed among groups.Results:The load to failure increased significantly with time in each group. There were significantly lower failure loads in the celecoxib group than in the control group at 3 weeks (0.533 vs. 0.700, P = 0.002), 6 weeks (0.607 vs. 0.763, P = 0.01), and 12 weeks (0.660 vs. 0.803, P = 0.002), and significantly lower percentage of type I collagen at 3 weeks (11.5% vs. 27.6%, P = 0.001), 6 weeks (40.5% vs. 66.3%, P = 0.005), and 12 weeks (59.5% vs. 86.3%, P = 0.001). Flurbiprofen axetil showed significant differences at 3 weeks (failure load: 0.600 vs. 0.700, P = 0.024; percentage of type I collagen: 15.6% vs. 27.6%, P = 0.001), but no significant differences at 6 and 12 weeks comparing with control group, whereas the ibuprofen groups did not show any significant difference at each time point.Conclusions:Nonsteroidal anti-inflammatory drugs can delay tendon healing in the early stage after rotator cuff repair. Compared with nonselective COX inhibitors, selective COX-2 inhibitors significantly impact tendon healing.

The Possible Effects of Non-steroidal Anti-inflammatory Drugs (NSAIDs) on the COX-2 Pathway of Skeletal Muscle Repair

“…Recently, a link has been found between COX enzymes and the repair of injured muscle tissue (Oak et al 2014, Lu et al 2015. A link has also been found between the COX-2 isoform and NSAIDs suggesting that NSAIDs may have a complex effect on the healing of muscle injuries characterized by early signs of improvement followed by subsequent late impairment in functional capacity and histology of muscle tissue (Prisk and Huard 2003).…”

“…Studies are currently investigating the underlying effects this link may have on the regeneration of muscle fibers after injury. With these new findings, questions regarding the efficiency of NSAIDs and the treatment of inflammation associated with muscle injury are being examined (Oak et al 2014, Lu et al 2015.…”

“…Recent studies have focused on the link between the COX-2 pathway of muscle repair and anti-inflammatory drugs. Studies by Oak et al (2014) and Lu et al (2015), have examined this process in-depth and found differing results regarding the effects of the COX-2 pathway on the repair of skeletal muscle tissue after injury. These studies also demonstrated that NSAIDs operate within the COX-2 pathway, which is a necessary pathway for muscle regeneration (Oak et al 2014, Lu et al 2015.…”

“…In a study done by Lu et al (2015) the effects of both selective and non-selective COX inhibitors on the process of post-injury muscle regeneration in rabbits were studied. Ibuprofen and flurbiprofen axetil were used as non-selective COX inhibitors and celecoxib was used as a selective COX-2 inhibitor (Lu et al 2015). The goal of this study was to determine the effects of he use of COX inhibitors on the repair of injured muscle tissue.…”

“…Ninety-six New Zealand white rabbits were used as the animal model for this study because of the anatomical similarity of the rabbit shoulder to the human shoulder (Lu et al, 2015) and the fact that shoulder injuries are among the top four injuries that occur along with hand, knee, and ankle injuries. The rabbits were divided into four groups and randomly assigned to one of three experimental COX inhibitor groups or the control group.…”