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Using a Knee Arthrometer to Evaluate Tissue-specific Contributions to Knee Flexion Contracture in the Rat
Published on: November 9, 2018
Cyclooxygenase-2 inhibitor celecoxib attenuates joint contracture following immobilization in rat knees
Junya Ozawa1, Akinori Kaneguchi2, Ryo Tanaka3
1Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Kurose- Gakuendai 555-36, Higashi-Hiroshima, Hiroshima, 739-2695, Japan. j-ozawa@hs.hirokoku-u.ac.jp.
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 °, 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 °, 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.
Insights
Celecoxib (CBX) administration in rats reduced immobilization-induced myogenic joint contracture by inhibiting muscle shortening. This suggests inflammation plays a role in contracture, and CBX is effective in prevention.
Area of Science:
- Biomedical Research
- Orthopedics
- Pharmacology
Background:
- Joint contracture is a common complication following immobilization.
- The role of cyclooxygenase-2 (COX-2) in contracture formation is not fully understood.
- Non-steroidal anti-inflammatory drugs (NSAIDs) may offer a therapeutic approach.
Purpose of the Study:
- To investigate the involvement of COX-2 in immobilization-induced joint contracture.
- To evaluate the effectiveness of celecoxib (CBX) in preventing myogenic and arthrogenic contracture.
- To analyze the impact of CBX on muscle and joint changes post-immobilization.
Main Methods:
- Thirty male rats were divided into immobilization (Im), Im+CBX, and control groups.
- Knee joints were immobilized in flexion for 3 weeks, with daily CBX administration in the Im+CBX group.
- Range of motion (ROM) was measured, and histological analyses of muscle and joint tissues were performed.
Main Results:
- Celecoxib significantly reduced myogenic ROM restrictions and knee flexor muscle shortening.
- Arthrogenic ROM restrictions and joint pathology were comparable between Im and Im+CBX groups.
- CBX administration inhibited reductions in muscle length and sarcomere number ratios.
Conclusions:
- Celecoxib partially mitigates myogenic ROM restriction and muscle shortening during immobilization.
- Inflammation and nociception appear to contribute to myogenic contracture independently of immobilization.
- Oral celecoxib demonstrates efficacy in preventing joint contracture in a rat model.

