Lumbar endplate microfracture injury induces Modic-like changes, intervertebral disc degeneration and spinal cord sensitization – An In Vivo Rat Model

bioRxiv preprint, 2023 · DOI: https://doi.org/10.1101/2023.01.27.525924 · Published: January 30, 2023

Spinal Cord Injury Pain Management Orthopedics

Simple Explanation

This study focuses on how damage to the endplate, a part of the spine, leads to disc degeneration and pain. The researchers created a model in rats to mimic endplate microfractures, similar to what happens in human spines with Modic changes. The rat model involved creating small fractures in the endplates of the lumbar vertebrae. These rats then showed signs of disc degeneration, changes in bone marrow similar to Modic changes seen in humans, and increased sensitivity to pain. The results suggest that endplate injuries can trigger a cascade of events leading to chronic pain and degeneration in the spine. This model can be used to test new treatments for back pain related to endplate damage.

Study Duration

8 weeks

Participants

Nineteen 5-month old male Sprague-Dawley rats

Evidence Level

In vivo rat study

Key Findings

1
EP microfracture induced IVD degeneration and height loss, Modic-like changes, and increased pain-like behaviors with spinal cord sensitization.
2
Modic-like changes were visible in both EP injury groups with hypointensity on T1w images and hyperintensity on T2w images in the both injury groups
3
The percentage area of SubP-ir (relative to dorsal horn) was significantly increased in rat spinal dorsal horns from EP injury groups compared to that of Sham

Research Summary

This study established a rat in vivo model of EP microfracture that caused MC type 1-like changes, IVD degeneration, and spinal cord sensitization. The presence of the EP microfracture injury caused crosstalk between vertebrae, IVD, and spinal cord sensitization, with TNFα injection increasing injury severity. The pain-like behaviors indicated spinal pathology and central sensitization occurred suggesting axial biomechanical instability and inflammation resulted in pain

Practical Implications

Therapeutic Screening

The rat model can be used to screen potential therapeutic interventions for EP microfracture related pain and degeneration.

Understanding Discogenic Pain

The model provides a platform to understand the crosstalk between vertebrae, IVD, and spinal cord in discogenic pain conditions.

Clinical Diagnosis

The findings highlight the need for phenotypic precision in diagnosing EP-driven IVD degeneration and addressing the high incidence of pain.

Study Limitations

1
This is a model system where EP injury was induced to create an EP microfracture with injury precision enhanced using one experienced spine surgeon and fluoroscopy guidance.
2
This study used male rats because of their larger size that made surgery slightly easier, and their more well-characterized von Frey mechanical sensitivity to IVD disruptions
3
this is a descriptive model characterization study, and we hope this model will be able to gain further insights into discogenic pain with future blocking and therapeutic screening studies.

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