# 3’ End Regulation in Nociceptor Plasticity

> **NIH NIH R01** · UNIVERSITY OF TEXAS DALLAS · 2020 · $403,215

## Abstract

Project Summary/Abstract
Poorly managed pain creates an enormous burden on our healthcare system and produces tremendous human
suffering. Following an injury, pain is caused by the production of inflammatory cytokines that induce changes in
the excitability of nociceptor neurons. A better understanding of molecular mechanisms that facilitate nociceptor
plasticity is vital for improved pain treatment. Post-transcriptional gene control has emerged as a dominant theme
in pain induced plasticity. We focus on Poly(A) binding proteins (PABPs), a conserved family of 3’ end associated
factors that regulate translation initiation and play prominent roles in development and memory. We will
determine binding specificities for PABPs present in dorsal root ganglion (DRG) neurons using an unbiased next-
generation sequencing approach. This information will be used to generate a novel class of chemically stabilized
RNAs called specificity-derived competitive inhibitor oligonucleotides (SPOT-ONs). Unlike genome editing or
RNA interference, SPOT-ONs are well tolerated and bypass the need for host-factors as they function as
“decoys”. A major advantage of pharmacological inhibition as opposed to targeted gene disruption is the ability
to simultaneously impair multiple homologues in a larger gene family. Our preliminary findings indicate that a bi-
specific PABP SPOT-ON provides robust anti-hyperalgesic effects in vivo. Based on this finding, we hypothesize
that PABPs are crucial mediators of plasticity in nociceptors. We describe preliminary development of SPOT-
ONs which reduce protein synthesis in nociceptors and act specifically on poly(A)-mediated mRNA translation
(Aim 1). We probe PABP mechanism of action through examination of localized translation and global
identification of targets in nociceptors (Aim 2). Finally, we determine how PABP inhibition impacts nociceptor
excitability and behavioral responses to injury (Aim 3).

## Key facts

- **NIH application ID:** 9878936
- **Project number:** 5R01NS100788-04
- **Recipient organization:** UNIVERSITY OF TEXAS DALLAS
- **Principal Investigator:** Zachary Campbell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $403,215
- **Award type:** 5
- **Project period:** 2017-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9878936

## Citation

> US National Institutes of Health, RePORTER application 9878936, 3’ End Regulation in Nociceptor Plasticity (5R01NS100788-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9878936. Licensed CC0.

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