Microglia Promote Increased Pain Behavior through Enhanced Inflammation in the Spinal Cord during Repeated Social Defeat Stress

The Journal of Neuroscience, 2019 · DOI: https://doi.org/10.1523/JNEUROSCI.2785-18.2018 · Published: February 13, 2019

Simple Explanation

This study investigates how repeated social defeat (RSD) stress in mice leads to increased pain sensitivity. It focuses on the role of microglia, immune cells in the spinal cord, in this process. The research found that RSD stress activates microglia in the spinal cord, leading to increased inflammation and pain sensitivity. Blocking microglia activity prevented the development of this pain. The findings suggest that microglia are key players in stress-induced pain and could be a target for new pain treatments. By understanding how microglia contribute to pain, scientists may develop strategies to alleviate chronic pain conditions.

Study Duration

Not specified

Participants

Male C57BL/6 (6–8 weeks old) and male CD-1 (12 months, retired breeders) mice

Evidence Level

Not specified

Key Findings

1
Repeated social defeat (RSD) stress increases mechanical allodynia (pain sensitivity) in mice.
2
RSD causes region-specific microglial activation in the spinal cord, particularly in the dorsal horn, which is involved in pain signaling.
3
Eliminating microglia with the CSF1R antagonist PLX5622 prevents the development of mechanical allodynia during RSD stress.

Research Summary

The study demonstrates that repeated social defeat (RSD) stress promotes a neuroinflammatory environment in the spinal cord, leading to increased pain sensitivity (mechanical allodynia) in mice. Microglial activation in the dorsal horn of the spinal cord, a region involved in pain signaling, is a key factor in RSD-induced allodynia, independent of peripheral monocyte recruitment. Pharmacological depletion of microglia prevents the development of mechanical allodynia during RSD stress and reduces the expression of inflammatory markers associated with nociceptive signaling.

Practical Implications

Therapeutic Target Identification

Microglia may serve as a therapeutic cellular target in the alleviation of pain associated with stress.

Understanding Stress-Induced Pain

The findings provide a novel cellular perspective on the mechanism of stress-induced pain.

Inflammation Management

The study highlights the importance of managing inflammation in the spinal cord to prevent or reduce pain sensitivity in individuals experiencing chronic stress.

Study Limitations

1
The study focuses on male mice, and the results may not be generalizable to females.
2
Systemic administration of PLX5622 depletes microglia not only in the spinal cord, but also the brain and myeloid cells in other tissues.
3
The precise mechanisms by which microglia contribute to the reorganization of circuitry within the spinal cord dorsal horn that mediates the development of mechanical allodynia remain unclear.

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