# Neuronal anatomy, connectivity, and phenotypic innervation of the knee joint

> **NIH NIH UC2** · BAYLOR COLLEGE OF MEDICINE · 2024 · $96,000

## Abstract

Project Summary
Severe pain caused by osteoarthritis (OA) affects over 15 million individuals in the United States alone. This
degenerative joint disorder not only poses a significant healthcare burden for the country’s aging society, but
also fuels the national opioid crisis, as no effective treatments exist to treat OA-induced joint pain. Disease-
modifying therapeutic development for OA typically involves mechanistic and preclinical studies in small animal
models (mouse, rat), followed by studies in large animal models (horse, pig) to confirm effectivity and safety.
Unfortunately, pain-modifying therapeutic development for OA has thus far been hampered by a limited
knowledge of the types of neurons that innervate the joint, the connections they form, and their functional or
circuit dynamics in the presence of joint disease. The RE-JOIN consortium strives to fill these knowledge gaps
by adapting and optimizing cutting-edge, multidisciplinary technologies to label, image, and profile joint-
innervating neurons and by applying them in small animal models and patients with OA. Here, we propose a
set of experiments that will be complimentary to RE-JOIN’s ongoing efforts. In this proposal, we aim to
leverage neuronal tracing and profiling technologies developed under parent grant (UC2-AR082200), applying
them to the equine carpal joint to identify and characterize joint-innervating neurons. We aim to identify the
dorsal root ganglia (DRG) that harbor carpal joint-innervating neurons (Viral neural tracing; Aim 1), develop
high-quality, complete transcriptomes of these DRGs that identify all tissue-specific isoforms (long-read RNA
sequencing; Aim 2), and perform multi-omic analysis of these DRGs to develop a spatial single cell reference
map that identifies the tissue’s individual cell types and their molecular fingerprints (spatial transcriptomics and
single nucleus RNA sequencing; Aim 3). The equine osteochondral chip model of post-traumatic OA has been
an excellent bridging translational model from small rodent to humans. The successful completion of research
proposed here will yield high-quality resources that will be shared with the scientific community, enabling future
studies to identify pain-mediating molecular and cellular changes that occur in the equine carpal joint
innervation during the development of joint disease. These resources will also enable translational researchers
to expand preclinical studies in equine models of OA to also include studies with chronic joint pain-modifying
therapeutic candidates, thereby increasing the likelihood of finding relevant new therapeutic targets to
effectively treat joint pain and/or solve the national opioid public health crisis.

## Key facts

- **NIH application ID:** 11093668
- **Project number:** 3UC2AR082200-01S1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Benjamin R Arenkiel
- **Activity code:** UC2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $96,000
- **Award type:** 3
- **Project period:** 2024-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11093668

## Citation

> US National Institutes of Health, RePORTER application 11093668, Neuronal anatomy, connectivity, and phenotypic innervation of the knee joint (3UC2AR082200-01S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11093668. Licensed CC0.

---

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