The micro (mi)RNAs expressed in the sciatic nerve of streptozotocin (STZ)-induced diabetic rats were evaluated in terms of their therapeutic potential in patients with diabetic neuropathic pain (DNP). Relative miRNA expression in sciatic nerve with DNP was analyzed using next-generation sequencing and quantitative PCR. Potential downstream targets of miRNAs were predicted using Ingenuity Pathway Analysis and the TargetScan database. In vitro experiments were performed using miR-133a-3p-transfected RSC96 Schwann cells. We performed micro-Western and Western blotting and immunofluorescence analyses to verify the role of miR-133a-3p. In vivo, the association between miR-133a-3p with DNP was analyzed via AAV-miR-133a-3p intraneural (intra-epineural but extrafascicular) injection into the sciatic nerve of normal rats or injection of an miR-133a-3p antagomir into the sciatic nerve of diabetes mellitus (DM) rats. miR-133a-3p mimics transfected into RSC96 Schwann cells increased VEGFR-2, p38α MAPK, TRAF-6, and PIAS3 expression and reduced NFκB p50 and MKP3 expression. In normal rats, AAV-miR-133a-3p delivery via intraneural injection into the sciatic nerve induced mechanical allodynia and p-p38 MAPK activation. In DM rats, miR-133a-3p antagomir administration alleviated DNP and downregulated p-p38 phosphorylation. Overexpression of miR-133a-3p in the sciatic nerve induced such pain. We suggest that miR-133a-3p is a potential therapeutic target for DNP.

评估链脲佐菌素（STZ）诱导的糖尿病大鼠坐骨神经中表达的微小（mi）RNA在糖尿病性神经性疼痛（DNP）患者中的治疗潜力。使用下一代测序和定量PCR分析了DNP在坐骨神经中的相对miRNA表达。使用Ingenuity Pathway Analysis和TargetScan数据库预测了miRNA的潜在下游靶标。使用miR-133a-3p转染的RSC96雪旺氏细胞进行了体外实验。我们进行了微蛋白免疫印迹和免疫印迹分析，以验证miR-133a-3p的作用。体内，通过将AAV-miR-133a-3p向正常大鼠的坐骨神经内神经内（神经内膜，但束外）注射或将miR-133a-3p antagomir注射至坐​​骨神经，分析了miR-133a-3p与DNP之间的关联糖尿病（DM）大鼠。转入RSC96雪旺细胞中的miR-133a-3p模拟物增加了VEGFR-2，p38αMAPK，TRAF-6和PIAS3的表达，并降低了NFκBp50和MKP3的表达。在正常大鼠中，通过将神经内注射到坐骨神经中的AAV-miR-133a-3p递送引起机械性异常性疼痛和p-p38 MAPK激活。在DM大鼠中，miR-133a-3p antagomir给药可减轻DNP并下调p-p38磷酸化。miR-133a-3p在坐骨神经中的过表达引起了这种疼痛。我们建议miR-133a-3p是DNP的潜在治疗靶标。