This study was performed to characterize the effect of microRNA‐101 (miR‐101) on the pain hypersensitivity in CCI rat models with the involvement of mitogen‐activated protein kinase phosphatase 1 (MKP‐1) in spinal cord microglial cells. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) in the developed CCI models were determined to assess the hypersensitivity of rats to mechanical stimulation and thermal pain. To assess inflammation, the levels of interleukin (IL)‐1β, IL‐6 and tumour necrosis factor‐α (TNF‐α) in the spinal dorsal horns of CCI rats and lipopolysaccharide (LPS)‐activated microglial cells were examined. miR‐101 and MKP‐1 gain‐ and loss‐of‐function experiments were conducted in in vivo and in vitro settings to examine the roles of miR‐101 and MKP‐1 in CCI hypersensitivity and inflammation. The results showed that miR‐101 was highly expressed in the spinal dorsal horn and microglial cells of CCI rat models. Furthermore, overexpression of miR‐101 promoted the pain hypersensitivity in CCI rat models by reducing MWT and TWL. The overexpression of miR‐101 also promoted inflammation in LPS‐exposed microglial cells, as indicated by increased levels of IL‐1β, IL‐6 and TNF‐α. MiR‐101 was shown to target MKP‐1, inhibiting its expression. Moreover, miR‐101 promoted pain hypersensitivity in CCI rat models by inhibiting MKP‐1 expression and activating the mitogen‐activated protein kinase (MAPK) signalling pathway. Taken together, miR‐101 could potentially promote hypersensitivity and inflammatory response of microglial cells and aggravate neuropathic pain in CCI rat models by inhibiting MKP‐1 in the MAPK signalling pathway.

中文翻译：

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MiR-101通过MKP-1介导的MAPK途径促进慢性压迫性损伤大鼠的疼痛超敏反应。

这项研究的目的是通过在脊髓小胶质细胞中参与丝裂原激活的蛋白激酶磷酸酶1（MKP-1）的作用来表征microRNA-101（miR-101）对CCI大鼠模型中疼痛超敏反应的影响。确定已开发的CCI模型中的机械退缩阈值（MWT）和热退缩潜伏期（TWL）以评估大鼠对机械刺激和热痛的超敏性。为了评估炎症，检查了CCI大鼠脊髓背角和脂多糖（LPS）激活的小胶质细胞中白介素（IL）-1β，IL-6和肿瘤坏死因子-α（TNF-α）的水平。在体内和体外环境中进行了miR-101和MKP-1功能获得和丧失的实验，以检查miR-101和MKP-1在CCI过敏和炎症中的作用。结果表明，miR-101在CCI大鼠模型的脊髓背角和小胶质细胞中高表达。此外，miR-101的过表达通过减少MWT和TWL促进了CCI大鼠模型的疼痛超敏反应。IL-1β，IL-6和TNF-α水平升高表明，miR-101的过表达也促进了LPS暴露的小胶质细胞的炎症。已证明MiR-101靶向MKP-1，抑制其表达。此外，miR-101通过抑制MKP-1表达并激活有丝分裂原激活的蛋白激酶（MAPK）信号通路来促进CCI大鼠模型的疼痛超敏反应。总之，miR-101可能通过抑制MAPK信号通路中的MKP-1来促进小胶质细胞的超敏性和炎症反应，并加重CCI大鼠模型的神经性疼痛。