# Intra-Articular Drug Delivery Modulating Immune Cells in Inflammatory Joint Disease

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $228,759

## Abstract

PROJECT SUMMARY
Pain is a key symptom associated with joint arthropathies and can persist despite optimal control of
inflammation by disease modifying anti-rheumatic drugs (DMARDs). Analgesic agents and corticosteroids are
often used to supplement DMARDs for short-term pain relief but lack disease modifying properties and their
sustained use carries adverse risks. There is an unmet need for agents that can achieve durable control of
pain. While the underlying mechanisms are complex, immune cells can affect the sensitization and/or
activation of sensory neurons that innervate joint structures and influence pain progression. The objective of
this application is to test the feasibility of leveraging immunoregulation for pain control. The project is related to
the parent grant, which seeks to validate a new strategy of intra-articular (IA) drug delivery of an
immunomodulatory agent that could promote disease remission in autoimmune arthritis through the
enhancement of disease-protective regulatory T cells (Treg). This supplement will expand the scope of the
existing aims of the parent grant and will study the T cell-pain axis in arthritis. Aim 1 will evaluate the temporal
profile of pain behaviors in the SKG mouse model of T cell driven arthritis and correlate pharmacologic
responsiveness to the agent with pain assessments and histopathological evaluations. Aim 2 will use SKG
Treg fate mapping mice to systematically assess the role of Treg stability in pain alleviation. Aim 3 will
compare pain progression in SKG mice between the Treg enhancing agent and a standard-of-care
immunosuppressive DMARD. Overall, these studies will advance our goal of generating supporting evidence
for T cell-focused immune mechanisms of pain and bidirectional interaction between tissue damage and pain
mechanisms.

## Key facts

- **NIH application ID:** 10856753
- **Project number:** 3R01AR081887-01S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Nisarg J. Shah
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $228,759
- **Award type:** 3
- **Project period:** 2023-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10856753

## Citation

> US National Institutes of Health, RePORTER application 10856753, Intra-Articular Drug Delivery Modulating Immune Cells in Inflammatory Joint Disease (3R01AR081887-01S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10856753. Licensed CC0.

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