GSE111216
Mouse transcriptomics reveals extracellular matrix organization as a major pathway involved in inflammatory and neuropathic pain
Chronic pain is a debilitating and poorly-treated condition. The mechanisms underlying the development of chronic pain are not well understood. Nerve injury and inflammation cause alterations in gene expression in tissues associated with transmission of pain, supporting molecular and cellular mechanisms that maintain painful states. Previous studies in animal models and human patients suffering from different chronic pain conditions have examined changes in transcriptome associated with chronic pain. However, in most studies, the analyses were restricted to a single tissue or pain condition. In the current study, we performed next-generation sequencing of dorsal root ganglia, spinal cord, brain and blood in mouse models of nerve injury and inflammation-induced chronic pain. Comparative analyses of differentially expressed genes (DEG) across these tissues in two pain models identified the extracellular matrix organization (ECMO) pathway as the most commonly affected pathway. Interestingly, examination of GWAS datasets revealed an over-representation of DEGs within the ECMO pathway in SNPs most strongly associated with human back pain. Remarkably, manipulation of the extracellular matrix in the mouse significantly affected the development of pain hypersensitivity following nerve injury, supporting our gene expression findings. In summary, our comprehensive analysis of transcriptional landscape across different mouse pain models and tissues as well as human GWAS datasets identified extracellular matrix organization as a central molecular pathway in the development of chronic pain. Overall design: Complete Freund's Adjuvant (CFA) and Spared Nerve Injury (SNI) were performed on mice. CFA is surrogate for inflammation pain, while SNI for neuropathic pain. Untreated mice were used as controls. Mice tissues were collected. Transcriptomes were compared, in a tissue-based and pain-related manner.