Identification of Regulatory Elements in Primary Sensory Neurons Involved in Trauma-Induced Neuropathic Pain

TL;DR

This study identifies regulatory elements in sensory neurons that contribute to chronic pain after nerve injury.

Contribution

The study introduces a multiomic approach to uncover cis-regulatory elements and TF binding motifs linked to chronic pain in sensory neurons.

Findings

C/EBPγ binds to a differentially accessible sequence in injured sensory neurons.

Differential chromatin accessibility influences gene expression in dorsal root ganglion neurons.

Transcription factor motifs are associated with chronic pain processes in nerve injury.

Abstract

Chronic pain is a significant public health issue that is often refractory to existing therapies. Here we use a multiomic approach to identify cis-regulatory elements that show differential chromatin accessibility and reveal transcription factor (TF) binding motifs with functional regulation in the rat dorsal root ganglion (DRG), which contain cell bodies of primary sensory neurons, after nerve injury. We integrated RNA-seq to understand how differential chromatin accessibility after nerve injury may influence gene expression. Using TF protein arrays and chromatin immunoprecipitation-qPCR, we confirmed C/EBPγ binding to a differentially accessible sequence and used RNA-seq to identify processes in which C/EBPγ plays an important role. Our findings offer insights into TF motifs that are associated with chronic pain. These data show how interactions between chromatin landscapes and TF expression patterns may work together to determine gene expression programs in rat DRG neurons after nerve injury.

The online version contains supplementary material available at 10.1007/s12035-023-03673-5.

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