Effect of Interleukin-1β on Gene Expression Signatures in Schwann Cells Associated with Neuropathic Pain

Interleukin-1β (IL-1β) plays a critical role in the development of neuropathic pain through activation of Schwann cells (SCs) after nerve injury. Here, we applied an RNA sequencing (RNA-seq) approach to identify the effect of IL-1β on gene signatures of a rat SC line (RSC96) and the potential molecular mechanisms underlying the development of neuropathic pain. RNA-seq data demonstrated a total of 57 significantly differentially expressed genes (DEGs) with 35 up-regulated and 22 down-regulated between SCs treated with IL-1β, and control SCs without treatment. Bioinformatics analysis showed that key upregulated DEGs included those associated with immune and inflammation-related processes, neurotrophin production and SC proliferation. Five proteins encoded by key upregulated DEGs (Ceacam1, Hap1, Irs3, Lgi4 and Mif) were further verified by Western blot. Consistent with the RNA-Seq results, the expression of key genes was confirmed in SCs by immunofluorescence of the chronic constriction injury (CCI) sciatic nerve in rats. Furthermore, we demonstrated that treatment with IL-1β resulted in an increase in p38/ERK phosphorylation, and activators of p38/ERK enhanced the effect of IL-1β on the expression some of the key genes, whereas p38/ERK inhibitors reversed these effects. In conclusion, the present study highlights key genes involved in the development of neuropathic pain through activation of SCs after nerve injury. Identification of these genes and subsequent evidence of their mediation by IL-1β treatment promote our understanding of molecular mechanisms of nerve injury induced neuropathic pain, and highlight potential molecular targets for the treatment of neuropathic pain.