GSE123919
Translational profiling of dorsal root ganglia and spinal cord in a mouse model of neuropathic pain
Acute pain serves as a protective mechanism, guiding the organism away from actual or potential tissue injury. In contrast, chronic pain is a debilitating condition without any obvious physiological function. The transition to, and the maintenance of chronic pain require new gene expression to support biochemical and structural changes within the pain pathway. The regulation of gene expression at the level of mRNA translation has emerged as an important step in the control of protein expression in the cell. Recent studies show that signaling pathways upstream of mRNA translation, such as mTORC1 and ERK, are upregulated in chronic pain conditions, and their inhibition effectively alleviates pain in several animal models. Despite this progress, mRNAs whose translation is altered in chronic pain conditions remain largely unknown. Here, we performed genome-wide translational profiling of dorsal root ganglion (DRG) and spinal cord dorsal horn tissues in a mouse model of neuropathic pain, spared nerve injury (SNI), using the ribosome profiling technique. We identified distinct subsets of mRNAs that are differentially translated in response to nerve injury in both tissues. We discovered key converging upstream regulators and pathways linked to mRNA translational control and neuropathic pain. Our data are crucial for the understanding of mechanisms by which mRNA translation promotes persistent hypersensitivity after nerve injury. Overall design: Four conditions were analysed, with each condition having duplicate samples. That is, eight tissue samples were collected. The eight samples were lysed and the lysate was divided into two parts, one was used to prepare a ribosome footprint library and the other fraction was used to prepare whole mRNA library. Thus, we had 16 libraries in total for sequencing. The four conditions studied were: spinal_cord_SNI with spinal_cord_SHam as control and DRG_SNI with SRG_sham as control.