Transcutaneous electrical nerve stimulation improves lateral ankle sprain (LAS) in rats by regulating the CXCL10/NF-kB signaling pathway: a potential treatment for LAS.

OBJECTIVE: This study revealed the function and mechanism of transcutaneous electrical nerve stimulation (TENS) in a rat model of lateral ankle sprain (LAS). METHODS: The LAS rat model was randomly divided into Low/Medium/High intensity of TENS groups, Sham group, and Model control group. After 1, 2, and 3 weeks of treatment, the improvement of LAS rar was measured by gait analysis, morphology, micro-CT, osteogenesis markers, etc. The expressions of IL-1β/CXCL-10/NF-kB of ankle joint were analyzed by PCR, IF, IHC and WB. Furthermore, comprehensive profiling of differential gene expression in the LAS rat model was conducted through transcriptome sequencing. Following intra-articular reinfusion of chondrocytes induced by TENS and the downregulation of CXCL-10 expression, the improvements were analyzed. RESULTS: After TENS treatment, compared with the model control group, the ankle degeneration score increased in the medium/high intensity of TENS groups (P < 0.05). The degree of inclined plane test increased in the low intensity of TENS group (P < 0.05). The average step length, step frequency increased in the TENS group (P < 0.05). The bone mineral density (BMD)/ bone mineral content (BMC) increased in the TENS groups. The bio-mechanical indicators of LAS rats increased in the TENS groups (P < 0.05). The cartilage thickness of the LAS rat increased in the TENS groups (P < 0.05). There were 7 gene targets of LAS rat that were closely related to the IL-17 signaling pathway; TENS down-regulated the CXCL-10/IL-1β/NF-kB expressions (P < 0.0). After chondrocyte reinfusion which induced with TENS, similar improvements in LAS rats were obtained. CONCLUSION: TENS could improve the motor function and promote the osteogenic and chondrogenic effects in LAS rats. TENS inhibited the inflammation by regulating the IL-1β/CXCL-10/NF-kB expression. The chondrocyte reinfusion with low-expressed CXCL-10, which was induced by TENS, improved the LAS rat. TENS, chondrocyte reinfusion and CXCL-10 inhibitor had a potential effect on LAS in the clinic.