# Diversity Supplement to FKBP51 antagonism to prevent chronic pain: optimizing efficacy & evaluating safety and mechanisms R01NS118563

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $59,081

## Abstract

PROJECT SUMMARY/ABSTRACT
Therapeutic targets for pain that develops following traumatic stress exposures (TSE) have historically focused
on tissue injury-related pain generators, but increasing evidence suggests that physiologic systems involved in
the stress response play a critical role in chronic pain development after TSE, opening an exciting new landscape
of potential therapeutic targets. Within this landscape, no target appears more promising than FK506-binding
protein 51 (FKBP51), an intracellular protein known to affect glucocorticoid negative feedback inhibition. The
investigators’ data demonstrate that FKBP51 inhibition reverses hyperalgesia after TSE, and suggest that
FKBP51 inhibition after TSE can prevent enduring stress-induced hyperalgesia (ESIH). The investigators’ data
further demonstrate that the effects of FKBP51 inhibition on ESIH after TSE are time, dosing, and duration-
dependent. Available literature indicate that increased FKBP51 levels are associated not only with chronic pain
after TSE, but also with other post-traumatic neuropsychiatric disorders often comorbid with chronic pain and
opioid use/abuse, including posttraumatic stress, depression, and anxiety. Importantly, preliminary data from the
investigative team indicate that FKBP51 inhibition does not have adverse cardiac effects or other adverse health
or behavioral effects.
Building on these data, the parent R01 will perform the next critical steps in evaluating FKBP51 as a therapeutic
target, including (1) evaluating the influence of dose, timing, and duration of FKBP51 inhibition after TSE on
ESIH development, (2) assessing candidate mechanisms mediating the preventive effect of FKBP51 inhibition
on chronic pain development, and (3) performing extensive testing of safety and addiction liability.
In this Administrative Supplement to Promote Diversity, the candidate will expand upon the proposed
mechanistic work by performing innovative experiments that are within the scope but not redundant with studies
proposed in the parent grant. In particular, the candidate will perform experiments to gain a broader
understanding of how FKBP51 influences gene expression patterns across time following TSE and across
central and peripheral tissues related to pain processes. The candidate will also perform cutting edge molecular
immunological studies assessing intracellular signaling networks influenced by FKBP51. The conduct of these
experiments along with extensive training opportunities, are designed to promote the candidate’s education and
future career trajectory toward being an independent academic scientist. Successful completion of the studies
proposed in this Administrative Supplement for Diversity will move the field forward in understanding the
molecular mechanisms by which FKBP51 influences post-TSE pain development.

## Key facts

- **NIH application ID:** 10622997
- **Project number:** 3R01NS118563-01A1S1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Sarah Linnstaedt
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $59,081
- **Award type:** 3
- **Project period:** 2020-09-30 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10622997

## Citation

> US National Institutes of Health, RePORTER application 10622997, Diversity Supplement to FKBP51 antagonism to prevent chronic pain: optimizing efficacy & evaluating safety and mechanisms R01NS118563 (3R01NS118563-01A1S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10622997. Licensed CC0.

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