Gene expression after nerve injury is regulated at different levels including transcription, mRNA translation and post-translational modifications. Studying all levels of regulation provides a comprehensive profile of nerve injury-induced changes in gene expression and facilitates the understanding of the neuropathic pain pathophysiology and finding better treatments.
Chronic pain triggered by nerve injury (neuropathic pain) is a debilitating and difficult to treat condition. Nerve injury can facilitate pain transmission via a variety of mechanisms including changes in gene expression. Gene expression is a complex and multi-step process which is regulated at various levels. Whereas most of the previous studies have focused on measuring changes in mRNA expression, other modes of gene expression regulation remain largely unknown. The efficiency of protein production from the copies of DNA (mRNA) is highly regulated via a process called mRNA translation. Recent studies have revealed that mRNA translation plays a key role in determining protein levels in the cell, and its dysregulation is observed in numerous physiological and pathological conditions. Blocking mRNA translation alleviates pain in animal models; however, the specific genes regulated by translational control mechanisms in pain remain elusive.
In the present study, we employed a specialized technique to measure mRNA translation in two pain-processing tissues, dorsal root ganglia (DRG), which is a cluster of neurons and spinal cord, in mice subjected to nerve injury. We measured both mRNA levels and the efficiency by which each mRNA is translated into a protein for all genes. Our study reveals distinct subsets of genes showing increase or decrease of translation after nerve injury in both DRG and spinal cord. Analysis of genes with altered translation identified several involved chains of reactions in the body, such as ERK (a key cellular enzyme) and biological functions, such as transcriptional regulation (the process of making copies of DNA), which are largely affected by translational control. In summary, our study reveals subsets of genes regulated at the level of mRNA translation and provides important insights into complex gene expression landscape after nerve injury in pain processing tissues.