# Validation of a Translational Model of Chronic Discogenic Low Back Pain

> **NIH NIH R61** · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · 2024 · $366,975

## Abstract

PROJECT SUMMARY
Chronic low back pain associated with disc degeneration is a leading cause of chronic pain and has a substantial
economic impact in the United States. Treatments for discogenic low back pain exhibit poor long-term efficacy
highlighting an important unmet medical need. However, efforts to improve pain management are hampered by
limited knowledge of the mechanisms underlying low back pain. Improving our understanding of the mechanisms
driving these chronic pain states is hampered by a lack of well characterized and validated preclinical models.
The current unmet need is a model of chronic low back pain that robustly mimics human presentation and
etiology. To develop a robust model of chronic discogenic low back pain, this proposal brings together experts
in orthopedics and animal models (Wachs) with neuroscience and behavioral measures of chronic pain (King).
The overarching goal of this proposal is to reproduce and validate a recently published rat model of disc
degeneration induced low back pain developed in Dr. Wachs’ lab. For the R61 portion of this proposal, we will
establish that this model can be reproduced in a second laboratory (King lab) to demonstrate external replication
of this new model of discogenic low back pain. To ensure consistency, Dr. Wachs and her veterinary surgeon
will both go to the King lab prior to the study start to train the King lab in the surgery and assays. Concurrent
animal studies will then be performed in the Wachs and King labs using the single puncture method in both sexes
of animals over an 18-week time course. Real-time disc degeneration will be monitored using either µCT or high-
speed x-ray. Pain-like behavior will be assessed using grip strength (evoked) and open arena (non-evoked)
testing. Post-processing will include histological analysis of disc degeneration, nerve growth, and inflammation.
Quantitative measures will be used to compare results between the Wachs and King labs to ensure robust model
reproducibility and provide tangible milestones for progression to the R33 phase. The R33 phase will consist of
external validation to establish face, construct, and predictive validity. Concurrent studies will be performed in
the Wachs and King labs over an 18-week time course. In this phase, we will increase resolution, frequency, and
quantification of assays to more accurately compare to human disease. For example, MRI will be used to
examine changes in disc degeneration and water content over time which, although more expensive, is more
directly comparable to the gold standard in human disease assessment. In addition, we will perform behavioral
analyses every three weeks to compare with the time course in humans. Histological analyses will be broadened
to include more robust analysis that will determine specific localization of nerves, blood vessels, and
inflammatory cells to allow comparison to previously published data of human biological features of discogenic
pain. Finally, we will use c...

## Key facts

- **NIH application ID:** 10872767
- **Project number:** 1R61NS133264-01A1
- **Recipient organization:** ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
- **Principal Investigator:** TAMARA E KING
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $366,975
- **Award type:** 1
- **Project period:** 2024-09-20 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10872767

## Citation

> US National Institutes of Health, RePORTER application 10872767, Validation of a Translational Model of Chronic Discogenic Low Back Pain (1R61NS133264-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10872767. Licensed CC0.

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