# Modulation of local adenosine signaling to attenuate fracture pain

> **NIH NIH R01** · DUKE UNIVERSITY · 2022 · $66,163

## Abstract

ABSTRACT OF PARENT GRANT (Modulation of local adenosine signaling to attenuate fracture pain
R01AR079189)
Management of pain arising from orthopedic fractures remains a challenge as common analgesic medications
such as non-steroidal anti-inflammatory drugs (NSAIDs) and opiates either interfere with healing or possess
unwanted side effects such as dependence. Given the prevalence of pain associated with orthopedic surgeries
and bone fractures, there is an urgent need to develop therapeutic strategies that can mitigate pain
while promoting fracture healing. This motivated us to study the potential use of adenosine (ADO) as a
therapeutic agent for managing fracture pain. ADO is a naturally occurring small molecule that is released
upon injury and elicits analgesic effects in peripheral and central nerves. We and others have shown that
extracellular ADO is an effective osteoanabolic agent promoting bone formation and fracture healing. The
osteoanabolic function of ADO along with the analgesic function makes it an ideal molecule to treat fracture
pain. The overarching goal of the proposal is to assess the use of ADO for the management of pain in
fracture injuries by advancing the fundamental understanding of how ADO mitigates fracture pain and
developing new clinically viable therapeutic strategies. Towards this, Aim 1 of the proposal will develop and
characterize an injectable biomaterial for local delivery of ADO to the fracture site, and determine the dose-
dependent effect on fracture healing. To determine whether biomaterial-assisted local delivery of ADO provides
analgesic effects following fracture injury, studies in Aim 2 will perform behavioral tests for pain, tissue
analyses, in vitro analyses by developing DRG-on-Chip platforms, and RNA sequencing. Aim 3 will test
the hypothesis that ADO-mediated fracture pain mitigation involves A1 receptors (A1Rs) by using animals
with conditional knockout of A1R in sensory neurons, and elucidates its regulation of ion channels.
Completion of this proposal will establish a new therapeutic molecule for the care of fracture trauma, and
potentially change how bone injuries are treated. The broad impact of our studies using localized delivery of
ADO could be extended to the management of various types of acute and chronic pain that originate in the
peripheral or central nervous system.

## Key facts

- **NIH application ID:** 10543700
- **Project number:** 3R01AR079189-02S1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Shyni Varghese
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $66,163
- **Award type:** 3
- **Project period:** 2021-04-15 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10543700

## Citation

> US National Institutes of Health, RePORTER application 10543700, Modulation of local adenosine signaling to attenuate fracture pain (3R01AR079189-02S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10543700. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*