Role of receptor-interacting protein 1/receptor-interacting protein 3 in inflammation and necrosis following chronic constriction injury of the sciatic nerve.

Abstract

Nerve damage often leads to nervous system dysfunction and neuropathic pain. The serine-threonine kinases receptor-interacting protein 1 (RIP1) and 3 (RIP3) are associated with inflammation and cell necrosis. This study aimed to explore the role of RIP1 and RIP3 in sciatic nerve chronic constriction injury (CCI) in mice. On a total of thirty mice, sciatic nerve CCI was performed. The paw withdrawal threshold was measured using Von Frey filaments. The mRNA expression and protein levels of inflammatory factors RIP1 and RIP3 in the dorsal root ganglion (DRG), spinal cord (SC) and hippocampus (HIP) were also determined. We found that paw withdrawal threshold was significantly reduced from the second day after the operation, and the levels of tumour necrosis factor-α and interferon-γ in DRG, SC and HIP were significantly increased on the eighth and 14th days in CCI mice. Furthermore, the downstream signalling molecules of RIP1 and RIP3, GTPase dynamin-related protein-1, NLR family pyrin domain containing-3 (NLRP3) and nuclear factor κB-p65 were upregulated. Increased protein levels of programmed cell death protein 1, which indicate cell death of peripheral and central nervous tissue, were induced by CCI of the sciatic nerve. Overall, this study showed that RIP1 and RIP3 were highly expressed in DRG, SC and HIP of the sciatic nerve in CCI mice and may be involved in chronic neuroinflammation and neuronecrosis.