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Papers of the Week

Papers: 24 Jul 2021 - 30 Jul 2021

Animal Studies

2021 Jul 28

FEBS Open Bio

RIP3-mediated necroptosis increases neuropathic pain via microglia activation: necrostatin-1 has therapeutic potential.


Neuropathic pain (NP) is a clinical symptom that accompanies many diseases. We investigated the effect of receptor-interacting protein kinase 3 (RIP3)-regulated necroptosis on NP, and explore its relationship with microglia, in order to provide a theoretical basis for further research and provide new insights into the treatment of NP. In this study, the spared nerve injury (SNI) model was used along with intervention with necrostatin and the inhibitor of necroptosis necrostatin-1 (Nec-1). Pain behavior tests were performed 1 and 3 days before the nerve injury (or sham) operation, and on days 1, 3, 5, 7, 10 and 14 after the operation. The spinal cord tissues were collected for detection of RIP3 expression and distribution, changes in the number of microglia cells, activation of necroptosis, and the level of pro-inflammatory factors. Collected spinal cord tissues were analysed using western blot, immunohistochemistry, immunofluorescence, immunoprecipitation assays and ELISA, respectively. We found that, compared with the sham group, the expression of RIP3 protein in the spinal cord of rats in the SNI group increased from 3 days to 14 days after surgery. Immunofluorescence staining showed that RIP3 was co-expressed with the microglia and the number of microglia increased significantly in the SNI model group. The results of immunoprecipitation assays suggested that a RIP3-mediated necroptosis pathway promotes NP. After treatment with Nec-1, the expression of RIP3 protein and the number of microglia was significantly reduced, and the expression levels of TNF-α, IL-1β and IL-6 in spinal dorsal horns were significantly decreased. These results indicate that RIP3 promotes necroptosis to increase the occurrence of NP via microglia.