# Immune-modulation in canine models of painful intervertebral disc degeneration

> **NIH NIH R21** · OHIO STATE UNIVERSITY · 2020 · $171,600

## Abstract

Project Summary/Abstract
Chronic low back pain continues to exert a significant socio-economic burden on society as its contribution to
the opioid crisis grows. This is because studies have failed to address the underlying mechanisms associated
with pain generation. Intervertebral disc (IVD) degeneration is highly associated with low back pain (LBP), and
neurovascular ingrowth into this usually avascular and aneural organ, has been identified in patients with
chronic pain. However, the specific pathways propagating ingrowth and pain have yet to be identified. Mast
cells regulate inflammation and pain in musculoskeletal diseases such as rheumatoid arthritis and
osteoarthritis. Both our published and supportive work have demonstrated significantly increased levels of
mast cell marker tryptase in the IVDs of human and canine patients with painful disc degeneration suggesting
that mast cells function to enhance catabolism, inflammation and pain pathways in discogenic back pain.
 The overall goal of this proposal is to use clinically relevant and novel chondrodystrophic
canine in vitro and in vivo animal models, to determine the role of mast cells and down-stream
pathway protease-activated receptor 2 in LBP and how they can be modulated for therapeutic effect.
This goal aligns well with high risk, high reward nature of the proposal as immune-modulation has never been
applied to the IVD as a non-addictive strategy to treat LBP. Furthermore, the chondrodystrophic dog is
currently under-utilized as an intermediate animal model of LBP despite its similarities to painful disc
degeneration in humans and its relevance as a client-owned “patient” population; this is largely because robust
validation of behavioral assessments of pain are lacking. Our studies aim to address this gap while catalyzing
innovation and improving scientific knowledge in this area.
 The first specific aim uses a novel high-through Bioreactor to investigate how co-culture of canine mast
cell-nucleus pulposus under dynamic physiological load regulates catabolism, inflammation and neurovascular
ingrowth in painful disc degeneration. In addition, mechanistic inhibition studies will be conducted to determine
efficacy of FDA-approved drug Cromolyn sodium and protease-activated rector 2 antagonist on these mast cell
induced effects. The second specific aim involves deep phenotyping the chondrodystrophic dog model of
painful disc degeneration using a comprehensive assessment of pain behaviors (hyperalgesia, activity, posture
and neuronal excitability) in addition to IVD structure/functional changes using histology, mechanics and MRI
followed by screening with immune-modulatory drugs. These studies are both significant and innovative
because they combine a unique multi-disciplinary team of medical and veterinary clinicians, a spine biologist, a
neuroscientist, veterinary immunologist and histo-pathologist, and a biostatistician to investigate the role of the
unexplored mast cell in the pathoph...

## Key facts

- **NIH application ID:** 10042520
- **Project number:** 1R21AR077809-01
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Devina Purmessur (Walter)
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $171,600
- **Award type:** 1
- **Project period:** 2020-08-07 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10042520

## Citation

> US National Institutes of Health, RePORTER application 10042520, Immune-modulation in canine models of painful intervertebral disc degeneration (1R21AR077809-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10042520. Licensed CC0.

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