RESUMEN
Neuropathic pain is a kind of chronic pain because of dysfunctions of somatosensory nerve system. Recently, many studies have demonstrated that microRNAs (miRs) play crucial roles in neuropathic pain development. This study was designed to investigate the effects of miR-134-5p on the process of neuropathic pain progression in a rat model established by chronic sciatic nerve injury (CCI). First, we observed that miR-134-5p was significantly decreased in CCI rat models. Overexpression of miR-134-5p strongly alleviated neuropathic pain behaviors including mechanical and thermal hyperalgesia. Meanwhile, inflammatory cytokine expression, such as IL-6, IL-1ß and TNF-α in CCI rats were greatly repressed by upregulation of miR-134-5p. Twist1 has been widely regarded as a poor prognosis biomarker in diverse diseases. Here, by using bioinformatic analysis, 3'-untranslated region (UTR) of Twist1 was predicted to be a downstream target of miR-134-5p in our study. Here, we found that overexpression of miR-134-5p was able to suppress Twist1 dramatically. Furthermore, it was exhibited that Twist1 was increased in CCI rats time-dependently and Twist1 was inhibited in vivo. Subsequently, downregulation of Twist1 in CCI rats could depress neuropathic pain progression via inhibiting neuroinflammation. In conclusion, our current study indicated that miR-134-5p may inhibit neuropathic pain development through targeting Twist1. Our findings suggested that miR-134-5p might provide a novel therapeutic target for neuropathic pain.
RESUMEN
BACKGROUND: Proteomics analysis may provide important information regarding the pathogenesis of chronic myofascial pain and the mechanisms underlying the treatment effects of dry needling. MATERIALS AND METHODS: This study used a rat model of myofascial trigger points (MTrPs) to perform a proteomics analysis. Three biological replicate experiments were used to compare the proteomes of healthy control rats, a rat model of MTrP, MTrP model rats following dry needling of MTrPs, and MTrP model rats following dry needling of non-MTrPs. Tandem mass tag (TMT) labeling technology based on nanoscale liquid chromatography-tandem mass spectrometry was used. Hierarchical clustering, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and protein-protein interaction network analysis were performed to characterize the proteins. To validate the TMT results, three candidate biomarker proteins were verified using parallel reaction monitoring and Western blot analysis. RESULTS: A total of 2,635 proteins were identified. GO and KEGG enrichment analyses showed that the glycolysis/gluconeogenesis pathways played dominant roles in the pathogenesis of chronic myofascial pain. The three candidate biomarker proteins were the pyruvate kinase muscle isozyme (encoded by the PKM gene), the muscle isoform of glycogen phosphorylase (encoded by the PYGM gene), and myozenin 2 (encoded by the MYOZ2 gene). The validation results were consistent with the TMT results. CONCLUSION: This is the first proteomics study that has investigated the pathogenesis of chronic myofascial pain and the mechanisms underlying the treatment effects of dry needling in an in vivo rat model of MTrPs, which might promote our understanding of the molecular mechanisms underlying chronic myofascial pain.