Cyclooxygenase-2 inhibitor celecoxib attenuates joint contracture following immobilization in rat knees

Background: The aim of this study is to clarify the following two points: First, whether a cyclooxygenase-2 mediated pathway is involved in the formation of immobilization-induced joint contracture and, second, the effectiveness of oral administration of non-steroidal anti-inflammatory drug celecoxib (CBX) for the prevention of myogenic and arthrogenic contracture following immobilization in a rat model. Methods: Thirty male rats were randomly divided into three groups: immobilization (Im), Im + CBX, and control (n = 10 each). External fixation immobilized the right knee joint of Im and Im + CBX groups in flexion for 3 weeks. 50 mg/kg of CBX was administrated daily to the Im + CBX group during this period. The passive range of motion (ROM) of knee joints was measured before and after transection of knee flexor muscles and myogenic and arthrogenic ROM restrictions were calculated. The semitendinosus muscles and knee joints were investigated histologically to elucidate factors responsible for contracture. Results: Myogenic ROM restrictions were exhibited both in Im and Im + CBX groups (44 +/- 5 and 36 +/- 8 degrees, respectively), but restrictions significantly decreased in the Im + CBX group compared to the Im group. Significant reductions of the muscle length ratios (Rt/Lt) and sarcomere number ratios (Rt/Lt) in knee flexor semitendinosus muscle, which are responsible for myogenic contracture, were also seen both in Im group (92 +/- 5 and 92 +/- 4 %, respectively) and Im + CBX group (97 +/- 3 and 97 +/- 3 %, respectively), but were inhibited by CBX administration (P < 0.05). Im and Im + CBX groups exhibited arthrogenic ROM restrictions with no significant differences (82 +/- 3 and 83 +/- 5 degrees, respectively). Posterior synovial length shortening and pathological changes (hemorrhage in joint cavities and capsule edema) in the knee joints were comparable between Im and Im + CBX groups. Conclusions: Oral administration of celecoxib partially reduced myogenic ROM restriction concomitantly with knee flexor muscle shortening following immobilization. These results imply that inflammation and nociception are involved in myogenic contracture formation independently of joint immobilization, and that CBX is effective in preventing joint contracture following immobilization in rats.