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Neurobiol Pain. 2018 Aug-Dec;4:35-44. doi: 10.1016/j.ynpai.2018.04.001. Epub 2018 Apr 18.

Translational profiling of dorsal root ganglia and spinal cord in a mouse model of neuropathic pain.

Author information

1
Department of Anesthesia, McGill University, Montreal, QC H3A 0G1, Canada.
2
Patrick Wild Centre and Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh EH8 9XD, UK.
3
Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada.
4
Department of Psychology, McGill University, Montreal QC H3A 1B1, Canada.
5
Department of Physiology, McGill University, Montreal QC H3G 1Y6, Canada.
6
Alan Edwards Centre for Research on Pain, McGill University, Montreal QC H3A 0G1, Canada.
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Contributed equally

Abstract

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.

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