EZH2 drives transcriptional repression of trpc5 gene in morphine tolerance

Purpose: To identify differentially expressed genes regulated by morphine in mice. Methods: Mice were intrathecally injected with normal saline or morphine (10 ug/10 uL) for 7 days and then spinal cords L4-L5 were collected and subjected to mRNA-sequencing by geneseeq and data analysis. Results: We identified morphine upregulated 42 genes and downregulated 44 genes compared with saline group. KEGG enrichment analysis showed calcium signaling pathway was downregulated by morphine and we noticed that TRPC5 was one of the most significantly downregulated genes by morphine. We confirmed that intrathecal injection of morphine leads to Trpc5 transcriptional suppression via reducing GABA release, contributing to morphine tolerance. The profiles of spinal cords L4-L5 collected from saline-treated and morphine treated mice respectively were generated for High-throughput sequencing, in triplicate, and analyzed the morphine-regulated transcriptomes.