Abstract: BACKGROUND: Post-traumatic arthritis is one of the most common forms of osteoarthritis. In vivo and in vitro studies have shown that icariin can treat osteoarthritis through multiple targets and multiple pathways with no obvious side effects. However, the analgesic effect and mechanism of icariin on post-traumatic arthritis has not been reported. 
OBJECTIVE: To investigate the analgesic effect and mechanism of icariin on post-traumatic arthritis in rats. 
METHODS: Thirty male Sprague-Dawley rats were randomly divided into sham group (n=10), model group (n=10) and icariin group (n=10). The right knee anterior cruciate ligament was cut off in the model group and icariin group, while the right knee joint capsule was cut only in the sham group. The rats in the icariin group were given intragastric administration of icariin (100 mg/kg/d), and the sham and model groups were given the same amount of normal saline at the same time point for 8 weeks. Mechanical withdrawal threshold and thermal withdrawal latency were measured by mechanical stimulation and thermal radiation to evaluate the pain threshold of rats. Open field test was used to evaluate anxiety and depression. General observation and Pelletier scoring of the knee cartilage were performed. Safranin O-Fast green staining and Osteoarthritis Research Society International score were used to evaluate the degree of cartilage degeneration. ELISA was used to detect the contents of inflammatory factors interleukin-1β and tumor necrosis factor-α in synovial fluid and synovial tissue. The protein expression of monocyte chemotactic protein 1/chemokine C-C-motif receptor 2 ligand receptor axis in cartilage tissue was detected by western blot.
RESULTS AND CONCLUSION: The mechanical withdrawal threshold and thermal withdrawal latency of the icariin group were significantly higher than those of the model group (P < 0.05). Compared with the sham group, the total exercise distance, the total number of crossing squares and the residence time in the central area of the model group were significantly decreased (P < 0.05). Compared with the model group, the above three indexes were significantly increased in the icariin group (P < 0.05). Compared with the model group, the levels of interleukin-1β and tumor necrosis factor-α in knee synovial fluid and synovial tissue were significantly decreased in the icariin group (P < 0.05). Compared with the sham operation group, the articular cartilage surface of the model group was more uneven and deformed, the cartilage tissue was hypertrophy, hardened and dull, and a large amount of cartilage tissue was exfoliated, while the cartilage degeneration in the icariin group was significantly less than that in the model group. The results of Safranin O-Fast green staining and Osteoarthritis Research Society International score showed that the degeneration of knee cartilage in the model group was more severe than that in the sham group, while that in the icariin group was significantly less than that in the model group. Compared with the model group, the protein expression level of monocyte chemotactic protein 1/chemokine C-C-motif receptor 2 ligand receptor axis was significantly lower in the icariin group (P < 0.05). The above findings indicate that icariin can significantly reduce hyperalgesia in the rat model of post-traumatic knee arthritis, and its mechanism may be related to reducing the levels of interleukin-1β and tumor necrosis factor-α in the knee joint and inhibiting the protein expression of monocyte chemotactic protein 1/chemokine C-C-motif receptor 2 ligand receptor axis.

Key words: icariin, post-traumatic arthritis, pain, inflammatory factor, monocyte chemoattractant protein 1, chemokine C-C-motif receptor 2