Effect of Low-Intensity Pulsed Ultrasound on Post-Traumatic Intra-Articular Knee Adhesions in Rats

Intra-articular adhesions (IAA) caused by trauma or surgical invasion commonly elicit pain and motor dysfunction. However, effective treatments for preventing IAA remain elusive. This study investigated the effects of low-intensity pulsed ultrasound (LIPUS) therapy on IAA after immobilization following trauma.

A knee adhesion model was established in male Wistar rats, which were divided into LIPUS and sham groups. LIPUS was applied for 20 min/d (30 mW/cm² [spatial average temporal average], 1 MHz, duty cycle 20%, 5 times/wk, for 1, 2 and 3 wk). Another group of rats was treated with the same parameters for 3 or 7 d. After the treatment period, we evaluated the range of motion (ROM) of the knee joint, the length of the adhesion and the posterior knee joint capsule. RNA-seq and RT-quantitative polymerase chain reaction were performed to investigate the molecular mechanisms underlying the effects of LIPUS.

The knee ROM was significantly improved, and the adhesion length was reduced in the LIPUS group. RNA-seq identified 113 and 776 differentially expressed genes on days 3 and 7, respectively, highlighting pathways related to inflammatory, immune and fibrotic responses. IL-6 mRNA in the LIPUS group was significantly upregulated on day 3 and significantly downregulated at 1 wk. The TNFα, TGFβ and HIF1α levels did not differ between all groups. COL1A1 expression in the sham group significantly increased on day 7.

These results indicate that LIPUS therapy may affect inflammatory and fibrotic pathways and may serve as a rehabilitation approach to prevent the development of IAA.