Integrated analysis of microRNA and mRNA expression profiles in the rat spinal cord under inflammatory pain conditions

Recent studies using microarray-based approaches have demonstrated that microRNAs (miRNAs) are involved in pain processing pathways. However, a significant proportion of computational predictions of miRNA targets are false-positive interactions. To increase the chance of identifying biologically relevant targets, we performed an integrated analysis of both miRNA and mRNA expression profiles in the rat spinal cord during complete Freund's adjuvant (CFA)-induced inflammatory pain. We generated miRNA and mRNA arrays from the same corresponding samples on days 5 and 14 after CFA injection. Five miRNAs and 1096 mRNAs in the CFA 5d group and 16 miRNAs and 647 mRNAs in the CFA 14d group were differentially expressed based on a filter of at least a 1.5-fold change in either direction. An integrated analysis revealed 54 mRNA targets with an inverse correlation to the expression patterns of three miRNAs in the CFA 5d group. Seventy-five targets were inversely correlated to six miRNAs in the CFA 14d group. The miRNA-mRNA interaction networks revealed significant changes in miR-124, miR-149, miR-3584 and their target genes, IL-6R, ADAM19, LAMC1 and CERS2, in the CFA 5d group. In the CFA 14d group, significant changes were noted in miR-124, miR-29, miR-34, miR-30, miR-338 and their target genes, TIMP2, CREB5 and EFNB1. We also investigated an interaction pair, miR-124-3p and IL-6R, and the results showed that miR-124-3p could attenuate inflammatory pain and decrease IL-6R expression in the spinal cord. These specific miRNAs and their target genes provide possible avenues for the diagnosis and treatment of inflammatory pain.