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Updated: Oct 15, 2025
Intravital Imaging of Axonal Interactions with Microglia and Macrophages in a Mouse Dorsal Column Crush Injury
Published on: November 23, 2014
Heterogeneous macrophages contribute to the pathology of disc herniation induced radiculopathy
Li Jin1, Li Xiao1, Mengmeng Ding2
1Department of Orthopaedic Surgery, University of Virginia, Charlottesville, VA 22908, USA.
Background Context:
Macrophages play important roles in the progression of intervertebral disc herniation and radiculopathy.
Purpose:
To better understand the roles of macrophages in this process, we developed a new mouse model that mimics human radiculopathy.
Study Design/Setting:
A preclinical randomized animal study.
Methods:
Three types of surgeries were performed in randomly assigned Balb/c mice. These were spinal nerve exposure, traditional anterior disc puncture, and lateral disc puncture with nerve exposure (n=16/group). For the nerve exposure group, the left L5 spinal nerve was exposed without disc injury. For the traditional anterior puncture, L5/6 disc was punctured by an anterior approach as previously established. For lateral puncture with nerve exposure, the left L5 spinal nerve was exposed by removing the psoas major muscle fibers, and the L5/6 disc was punctured laterally on the left side with a 30G needle, allowing the nucleus to protrude toward the L5 spinal nerve. Mechanical hyperalgesia (pain sensitivity) of hind paws was assessed with electronic von Frey assay on alternative day for up to 2 weeks. MRI, histology, and immunostaining were performed to confirm disc herniation and inflammation.
Results:
Ipsilateral pain in the lateral puncture with nerve exposure group was significantly greater than the other groups. Pro-inflammatory cytokines IL-1β and IL-6 were markedly elevated at the hernia sites of both puncture groups and the spinal nerve of lateral puncture with never exposure group on postoperative day 7. Heterogeneous populations of macrophages were detected in the infiltration tissue of this mouse model and in tissue from patients undergone discectomy.
Conclusions:
We have established a new mouse model that mimics human radiculopathy and demonstrated that a mixed phenotype of macrophages contribute to the pathogenesis of acute discogenic radiculopathy.
Clinical Significance:
This study provides a clinically relevant in vivo animal model to elucidate complex interactions of disc herniation and radicular pain, which may present opportunities for the development of macrophage-anchored therapeutics to manage radiculopathy.
Insights
Researchers developed a new mouse model for radiculopathy, revealing that diverse macrophage populations drive disc herniation and nerve pain. This model aids in understanding and potentially treating radicular pain.
Area of Science:
- Neuroscience
- Immunology
- Orthopedics
Background:
- Macrophages are crucial in intervertebral disc herniation and radiculopathy progression.
- Understanding macrophage roles is key to addressing this condition.
Purpose of the Study:
- To develop a novel mouse model that accurately mimics human radiculopathy.
- To investigate the specific roles of macrophages in discogenic radiculopathy.
Main Methods:
- A preclinical randomized animal study involving three surgical groups in Balb/c mice.
- Assessment of mechanical hyperalgesia, MRI, histology, and immunostaining to evaluate disc herniation and inflammation.
- Development of a lateral disc puncture with nerve exposure model to induce radiculopathy.
Main Results:
- The lateral puncture with nerve exposure group exhibited significantly greater ipsilateral pain.
- Elevated levels of pro-inflammatory cytokines (IL-1β, IL-6) were observed in puncture groups.
- Heterogeneous macrophage populations were identified in the mouse model and human patient tissues.
Conclusions:
- A new, clinically relevant mouse model for radiculopathy has been established.
- Mixed macrophage phenotypes contribute to the pathogenesis of acute discogenic radiculopathy.
- This model offers insights for developing targeted macrophage-based therapeutics for radiculopathy.
