Relationship of Inﬂammatory Cytokines From M1-Type Microglia/Macrophages at the Injured Site and Lumbar Enlargement With Neuropathic Pain After Spinal Cord Injury in the CCL21 Knockout (plt) Mouse

Front. Cell. Neurosci., 2019 · DOI: 10.3389/fncel.2019.00525 · Published: November 21, 2019

Spinal Cord Injury Neurology Pain Management

Simple Explanation

Spinal cord injury (SCI) can lead to neuropathic pain (NeP). This pain may be caused by substances released from activated microglia and macrophages. This study examined mice with a genetic mutation (plt mice) that lack CCL21, a chemokine involved in microglia activation. The researchers assessed pain and immune cell responses after SCI. The study found that plt mice experienced less pain after SCI compared to wild-type mice. This reduction in pain was associated with fewer M1-type microglia/macrophages and reduced levels of inflammatory cytokines.

Study Duration

Not specified

Participants

54 C57BL/6 mice and 54 plt mice

Evidence Level

Original Research

Key Findings

1
SCI-induced hypersensitivities to mechanical and thermal stimulation were relieved in plt mice compared with wild-type mice.
2
A decrease of M1-type microglia/macrophages was seen in plt mice compared with wild-type mice.
3
Expression of M1-induced cytokines [tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ)] was decreased in plt mice.

Research Summary

The study investigated the role of CCL21 in neuropathic pain (NeP) after spinal cord injury (SCI) using CCL21 knockout (plt) mice. plt mice exhibited reduced mechanical and thermal hypersensitivity after SCI compared to wild-type mice, without affecting motor function. The findings suggest that CCL21 plays a key role in NeP after SCI by promoting M1-type microglia/macrophage infiltration and pro-inflammatory cytokine expression.

Practical Implications

Therapeutic Target Identification

CCL21 may serve as a potential therapeutic target for preventing or alleviating neuropathic pain after spinal cord injury.

Development of Targeted Therapies

The design of new therapies aimed at inhibiting CCL21 expression or its downstream signaling pathways could be a useful strategy to alleviate neuropathic pain.

Earlier Intervention Strategies

CCL21-blocking antibody treatment may be more effective in an earlier phase after injury.

Study Limitations

1
Experiments isolating cells of a particular day need to be provided to analyze M1 and/or M2 chemotaxis towards CCL21.
2
The influence of a CCL21 blocker in the chronic phase may be limited.
3
There are various cytokines associated with NeP after SCI, and it is important to avoid adverse effects by blocking cytokines with drugs.

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