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

Abstract

This study revealed the function and mechanism of transcutaneous electrical nerve stimulation (TENS) in a rat model of lateral ankle sprain (LAS). 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. 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. 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. In this study, a lateral ankle sprain (LAS) rat model was duplicated and treated with transcutaneous electrical nerve stimulation (TENS). After a period of treatment with TENS, the improvement of TENS in LAS rats was analyzed. The different regulated gene of articular cartilage was obtained by transcriptome analysis. In vitro, the CXCL-10/NF-kB expressions were analyzed and prepared as an intra-articular injection for LAS rats. Then, the chondrocyte whose CXCL-10/NF-kB expression were down-regulated and its therapeutic improvement was analyzed. The aim of this study is to elucidate the function and mechanism of TENS in LAS rats. This study found that TENS could improve the motor function and promote the osteogenic and chondrogenic effects on LAS rats. TENS inhibited the inflammation by regulating the IL-1β/CXCL-10/NF-kB expression. Reinfusion of chondrocytes with low levels of CXCL-10 yields comparable effects to TENS in LAS rats. Collectively, TENS, demonstrate a promising clinical potential for the treatment of LAS. Furthermore, chondrocyte reinfusion might become a therapeutic approach, substantial technical barriers currently limit its clinical applicability.