MiR‐101 promotes pain hypersensitivity in rats with chronic constriction injury via the MKP‐1 mediated MAPK pathway

• Published in: Journal of cellular and molecular medicine Vol. 24; no. 16; pp. 8986 - 8997
• Main Authors: Qiu, Shuang, Liu, Benjuan, Mo, Yanshuai, Wang, Xueqin, Zhong, Lina, Han, Xiao, Mi, Fuli
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.08.2020; John Wiley and Sons Inc
• Subjects: Animal models; Animals; Binding sites; Catheters; Cell culture; chronic constriction injury; Constriction; Dorsal horn; Dual Specificity Phosphatase 1 - metabolism; Female; Gene expression; Hypersensitivity; Inflammation; Inflammation - metabolism; Interleukin-1beta - metabolism; Intubation; Kinases; Laboratory animals; Latency; Lipopolysaccharides; MAP kinase; Mechanical stimuli; Microglia - metabolism; Microglial cells; MicroRNAs - metabolism; MicroRNA‐101; miRNA; Mitogen-Activated Protein Kinases - metabolism; mitogen‐activated protein kinase phosphatase 1; Nervous system; Neuralgia; Neuralgia - metabolism; NF-kappa B - metabolism; Original; Pain; pain hypersensitivity; Protein kinase; Rats; Rats, Sprague-Dawley; Rodents; Signal transduction; Signal Transduction - physiology; Spinal cord; Spinal Cord - metabolism; spinal cord microglial cell; Surgery; Tumor necrosis factor; Tumor Necrosis Factor-alpha - metabolism; Tumors; chronic constriction injury; mitogen-activated protein kinase phosphatase 1; MicroRNA-101; pain hypersensitivity; spinal cord microglial cell
• DOI: 10.1111/jcmm.15532
• ISSN: 1582-1838; 1582-4934

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.