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Updated: Apr 15, 2026
Rapid Isolation of Dorsal Root Ganglion Macrophages
Published on: September 7, 2019
Effects of differently activated rodent macrophages on sensory neurons: implications for arthritis pain
Julia Massier1, Annett Eitner1, Gisela Segond von Banchet1
1Jena University Hospital and Friedrich Schiller University of Jena, Jena, Germany.
Objective:
In arthritis, macrophages invade the affected joint. Experimental arthritis models have shown that macrophages also invade the dorsal root ganglia (DRGs) of the inflamed segments in which the perikarya of sensory neurons are located. It is unclear whether this macrophage invasion contributes to arthritis pain and/or furthers neuronal damage. The present study was undertaken to investigate how differently activated macrophages affect DRG neurons.
Methods:
We determined the phenotype of macrophages in the DRGs of rats with antigen-induced arthritis (AIA). In a DRG neuron-macrophage coculture system, we investigated whether differently activated macrophages (stimulated with either lipopolysaccharide [LPS]/interferon-γ [IFNγ], tumor necrosis factor [TNF], or interleukin-4) damage DRG neurons and/or stimulate them to release the mediator calcitonin gene-related peptide (CGRP), which promotes pain and neurogenic inflammation.
Results:
Macrophages in the DRGs of rats with AIA showed the phenotype of TNF-stimulated macrophages but did not express inducible nitric oxide synthase, which was found in cultured macrophages only after LPS/IFNγ activation. In neuron-macrophage cocultures, activation of macrophages stimulated DRG neurons to release CGRP within 1 hour, indicating neuronal activation by macrophages. Only 48-hour activation of macrophages with LPS/IFNγ increased the neuronal cell death rate in culture, provided that the macrophages were in direct contact with DRG neurons. This effect was dependent on nitric oxide.
Conclusion:
Macrophages have the potential to stimulate sensory neurons in the DRGs, and this may contribute to arthritis pain. If they are classically activated, such as after LPS/IFNγ stimulation, this may also further neuronal cell death. This is not the case in AIA but may occur in models involving damage of sensory neurons.
Insights
Macrophages in dorsal root ganglia (DRGs) can activate sensory neurons, potentially causing arthritis pain. Classically activated macrophages may also cause neuronal death, particularly in certain arthritis models.
Area of Science:
- Neuroimmunology
- Rheumatology
- Pain Research
Background:
- Macrophages infiltrate joints and dorsal root ganglia (DRGs) in arthritis.
- The role of DRG macrophage invasion in arthritis pain and neuronal damage is unclear.
Purpose of the Study:
- To investigate the effects of differently activated macrophages on DRG neurons.
Main Methods:
- Determined macrophage phenotype in rat DRGs during antigen-induced arthritis (AIA).
- Used DRG neuron-macrophage cocultures to assess macrophage activation (LPS/IFNγ, TNF, IL-4) effects on neuronal damage and calcitonin gene-related peptide (CGRP) release.
Main Results:
- AIA macrophages resembled TNF-stimulated macrophages; LPS/IFNγ-activated macrophages produced nitric oxide.
- Activated macrophages stimulated DRG neurons to release CGRP within 1 hour.
- 48-hour LPS/IFNγ activation of macrophages in direct contact with neurons increased neuronal cell death via nitric oxide.
Conclusions:
- Macrophages can activate DRG sensory neurons, potentially contributing to arthritis pain.
- Classically activated macrophages (e.g., LPS/IFNγ) may cause neuronal death, especially in models with sensory neuron damage, but not typically in AIA.
