# Elucidating how macrophages contribute to osteoarthritis pain

> **NIH NIH F32** · RUSH UNIVERSITY MEDICAL CENTER · 2022 · $72,082

## Abstract

Project Summary
Chronic joint pain from osteoarthritis (OA) represents an urgent unmet medical need. There are no treatments
that slow or blunt OA disease, and available analgesic strategies do not provide adequate pain relief. Joint pain
drives OA patients to seek medical help, yet our understanding of what mechanisms drive chronic joint pain in
OA remains poor. Cumulative data suggest that OA pain is established through local mechanisms in the joint,
while peripheral and central nervous system sensitization amplifies the pain and contributes to its chronicity. A
role for immune cells in modifying pain sensitization has been suggested, but not clearly elucidated. We have
generated compelling data showing increased F4/80+ macrophages in the dorsal root ganglia (DRG) at 8 weeks
after destabilization of the medial meniscus (DMM), a post-injury OA mouse model that progresses over 16
weeks. In addition, Ccr2-/- mice show reduced F4/80+ macrophages in the DRG at the same time point, and do
not develop persistent pain behaviors from 8-16 weeks post DMM. We believe that during this critical time, the
acute-to-chronic pain transition is occurring, and that macrophages play an important role in this transition
through DRG neuron sensitization. Therefore, the goal of this proposal is to test the Central Hypothesis:
increased levels of DRG macrophages in early-stage OA are critical to the acute-to-chronic pain transition and,
hence, targeting macrophages at the right time may blunt OA pain. Aim 1 seeks to determine the efficacy of
targeting macrophages to blunt OA pain by macrophage depletion studies using a sophisticated Macrophage
Fas-Induced Apoptosis (MaFIA) mouse model. Aim 2 seeks to examine how macrophages contribute to chronic
OA pain. Aim 2A will evaluate the differences between WT and Ccr2-/- mice and determine how Ccr2-/- mice are
protected from persistent OA pain. We will use single cell RNA-sequencing (scRNAseq) of Ccr2-/- DRGs post
DMM compared to WT DMM DRGs to examine significant differential expression patterns that may help explain
why Ccr2-/- mice are protected from chronic joint pain. In addition, Aim 2A will look for novel targets for OA pain
by studying human DRG tissues. Aim 2B will use elegant co-culture assays (DRG cell culture with bone marrow-
derived macrophages via transwell assay) to further characterize the functional dynamics involved in neuron-
macrophage crosstalk. I will gain new training in in vivo skills such as knee joint histology, mechanical allodynia
and knee hyperalgesia via von Frey or pressure application measurement (PAM), DRG immune phenotyping via
flow cytometry, and gene expression via bulk RNA-seq or scRNA-seq. Overall, the proposed work will generate
valuable new insights into the molecular mechanisms of how macrophages contribute to chronic pain
development, and inform future translational studies for drug development of improved therapies for OA pain.
Moreover, this fellowship will provide me with training...

## Key facts

- **NIH application ID:** 10465750
- **Project number:** 1F32AR081129-01
- **Recipient organization:** RUSH UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Terese Geraghty
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $72,082
- **Award type:** 1
- **Project period:** 2022-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10465750

## Citation

> US National Institutes of Health, RePORTER application 10465750, Elucidating how macrophages contribute to osteoarthritis pain (1F32AR081129-01). Retrieved via AI Analytics 2026-06-03 from https://api.ai-analytics.org/grant/nih/10465750. Licensed CC0.

---

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