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Published on: May 25, 2017
Intradiscal Cutibacterium acnes Sustains Modic Type 1-Like Lesions Over Time in a Rat Lumbar Endplate Injury Model
Irina Heggli1, Alon Lai1, Denise Iliff1
1Department of Orthopedics Icahn School of Medicine at Mount Sinai New York New York USA.
Background:
Modic changes (MC) are painful vertebral bone marrow lesions. Three interconvertible types represent different pathology stages with MC1 being the most painful, MC2 less painful, and MC3 asymptomatic. Bacterial (Cutibacterium acnes (C. acnes)-mediated) and non-bacterial etiologies are both suggested to induce MC1, but it remains unclear whether MC conversion is etiology-specific. This has important implications for patient management and the development of MC therapies.
Aims:
To assess MC-subtype lesion prevalence and pain-like behavior over time in an etiology-specific MC rat model.
Methods:
Four-to-five-month-old Sprague-Dawley rats underwent sham (n = 12) surgery or endplate injury followed by an intradiscal injection of 2.5 μL of either TNF-α (1000 ng/mL PBS) (n = 19) or C. acnes (3.2 × 108 CFU/mL in PBS) (n = 18) to mimic aspects of bacterial versus non-bacterial MC etiologies. MC-subtype prevalence was evaluated by magnetic resonance imaging at 1, 8, and 14 weeks post-injury. Disc degeneration, bone marrow lesion neutrophil elastase and CD19 immunoreactivity, spinal cord sensitization, and pain-like behavior (von Frey) were assessed, and contributors to pain-like behavior were identified (random forest).
Results:
C. acnes injection caused higher MC1-like lesion prevalence than TNF-α and Sham at all-time points and higher spinal cord substance P expression at 14 weeks post-injury. MC2-like lesions increased over time in TNF-α-injected discs and were more prevalent at 14 weeks post-injury than C. acnes. C. acnes injection resulted in bone marrow lesions with higher neutrophil elastase- and CD19 immunoreactivity. MC1-like lesions contributed strongest to pain-like behavior, although von Frey did not differ between groups.
Conclusion:
Intradiscal C. acnes injection sustained MC1-like lesions in an etiology-specific lumbar MC rat model, suggesting that patients with bacterial MC etiology may be more likely to persist in painful MC1.
Insights
Bacterial infections, like Cutibacterium acnes (C. acnes), may cause persistent painful Modic changes (MC1) in the spine. Non-bacterial causes like TNF-α led to less painful MC2 lesions over time.
Area of Science:
- Spinal pathology and pain research.
- Bacterial and non-bacterial etiologies of bone lesions.
- Animal models for human disease study.
Background:
- Modic changes (MC) are vertebral bone marrow lesions associated with pain.
- MC1 is the most painful subtype, MC2 less painful, and MC3 asymptomatic.
- Both bacterial (C. acnes) and non-bacterial factors are implicated in MC1, but etiology-specific progression is unclear.
Purpose of the Study:
- To investigate MC subtype prevalence and pain-like behavior in an etiology-specific rat model.
- To compare the effects of C. acnes versus TNF-α on Modic changes.
- To understand the long-term implications of different MC etiologies.
Main Methods:
- Rats received sham surgery or endplate injury followed by intradiscal injection of C. acnes or TNF-α.
- MC subtypes were assessed via MRI at 1, 8, and 14 weeks.
- Disc degeneration, inflammation markers, spinal cord sensitization, and pain behavior were evaluated.
Main Results:
- C. acnes induced higher MC1 prevalence and spinal cord substance P expression compared to TNF-α.
- TNF-α led to increased MC2 lesions over time, while C. acnes showed higher inflammatory markers.
- MC1 lesions were the primary contributor to pain-like behavior.
Conclusions:
- Intradiscal C. acnes sustained MC1-like lesions in the rat model.
- Bacterial etiologies may lead to more persistent painful Modic changes (MC1).
- Findings have implications for understanding MC progression and developing targeted therapies.

