Oxaliplatin-loaded monomethoxy (polyethylene glycol)–poly(d, l-lactic-co-glycolic acid) nanoparticles induced neuropathic pain through the pro-inflammatory effect of microglia in the spinal dorsal horn mediated by Zic2/membrane adapter protein 12

Abstract

The aim of this study is to investigate the effect and mechanism of oxaliplatin (OX)-loaded monomethoxy (polyethylene glycol)–poly(d, l-lactic-co-glycolic acid) (mPEG–PLGA) nanoparticles on neuropathic pain induced by pro-inflammatory action of Zic2/membrane adaptor protein 12 (DAP12) on microglia in the spinal dorsal horn. We have used websites, namely, String, Coexpedia, and Geneontology, for gene ontology (GO) and pathway enrichment analyses as well as co-expression analysis. The obtained core genes served as targets for OX-induced neuropathic pain. EMSEMBL and BDGF predicted the promoter site of DAP12. Further, mPEGPLGA nanoparticles loaded with OX were injected intravenously into the mice to construct a mouse model of OX-induced neuralgia. Real-time quantitative polymerase chain reaction (qrt-qpcr) was used to detect the transcription level of the target gene, while the target gene translation level was detected by western blot. The co-expression analysis of the first 250 genes revealed that the target genes were Tyrobp (DAP12), C1qb, Laptm5, Cd53, C1qc, Foxd1, Foxc1, Tbx15, Mafb, and Zic2. PROMO was used to predict the binding site of Zic2 at DAP12. As expected, the protein and mRNA expressions of Zic2, Tyrobp, IL-1β, TNF-α increased in OX mice. Based on the results of the investigation, we conclude that one of the mechanisms of OX-induced neuropathic pain may be related to IL-1β and TNF-α expression by microglial cells (in the spinal dorsal horn) through Zic2/DAP12.