# Translation Control of Pain Plasticity

> **NIH NIH R01** · UNIVERSITY OF TEXAS DALLAS · 2021 · $537,341

## Abstract

In neurons, synaptic and intrinsic plasticity is dependent on the regulated control of mRNA translation.
Over the past decade our work has focused on how translation regulation signaling is involved in neuronal
plasticity that drives chronic pain. Our findings demonstrate that inflammatory and neuropathic injuries
stimulate translation regulation signaling pathways in dorsal root ganglion (DRG) nociceptors, neurons that
detect injurious or potentially injurious stimuli. The result of activation of these pathways is increased
excitability of nociceptors, behavioral signs of ongoing pain and sensitization to mechanical and thermal
stimulation. This body of work, supports the idea that therapeutics targeting translation regulation signaling
pathways can be used for the efficacious treatment of chronic pain. Our overarching hypothesis for this
continuing project is that MNK1 activation in nociceptors is the key regulatory factor for the translation of a
subset of mRNAs that encode proteins that augment the excitability of nociceptors causing enhanced pain
phenotypes. We will test this hypothesis using new transgenic mouse lines, cell type-specific translating
ribosome affinity purification (TRAP), highly specific inhibitors of MNK1/2 and new generation inhibitors that are
specific for MNK1. Our preliminary data indicates that the key MNK isoform for nociceptive behavioral plasticity
is MNK1. Based on our electrophysiology experiments we hypothesize that the site of action for this kinase is
in DRG neurons. Our first specific aim will test the hypothesis that MNK1 expression in nociceptors is a key
driver of behavioral expression of chronic pain. We have created a TRAP line that expresses L10a-tagged
ribosomes in neurons that express the Scn10a gene (Scn10aTRAP). In our second specific aim we will examine
how translation of specific mRNAs is regulated in preclinical neuropathic pain models with and without genetic
or pharmacological manipulations of MNK-eIF4E signaling. This will yield unprecedented molecular insight into
plasticity-driven changes in gene expression in nociceptors in neuropathic pain. The third specific aim will
focus on pharmacologically or genetically targeting mechanisms discovered using approaches in aims 1 and 2.
For instance, our TRAP approach captures translational upregulation of the Mrgrpd receptor in a neuropathic
model. We will use knockout mice to investigate the role of this receptor in sensory neuron excitability in
neuropathic pain. The proposed specific aims will highlight a key regulatory pathway for neuropathic pain and
give new insight into novel therapeutic targets for neuropathic pain.

## Key facts

- **NIH application ID:** 10133154
- **Project number:** 5R01NS065926-11
- **Recipient organization:** UNIVERSITY OF TEXAS DALLAS
- **Principal Investigator:** Theodore J. Price
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $537,341
- **Award type:** 5
- **Project period:** 2010-03-15 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133154

## Citation

> US National Institutes of Health, RePORTER application 10133154, Translation Control of Pain Plasticity (5R01NS065926-11). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10133154. Licensed CC0.

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