Spinal Cord Stimulation Enhances Microglial Activation in the Spinal Cord of Nerve-Injured Rats

Neurosci. Bull., 2020 · DOI: https://doi.org/10.1007/s12264-020-00568-6 · Published: September 5, 2020

Simple Explanation

This study investigates how spinal cord stimulation (SCS) affects microglia, immune cells in the spinal cord, in rats with nerve injury. The researchers aimed to understand if SCS's pain-relieving effects involve changes in microglial activity. The findings suggest that conventional SCS may increase the activity of a specific type of microglia (M1-like) in the spinal cord. This increase might counteract SCS's ability to reduce pain. The study also found that blocking microglial activation with a drug called minocycline prolonged the pain relief provided by SCS. This suggests that modulating microglial activity could improve the effectiveness of SCS for treating neuropathic pain.

Study Duration

Not specified

Participants

Male Sprague-Dawley rats (2–3 months old)

Evidence Level

Not specified

Key Findings

1
Conventional SCS transiently attenuated mechanical hypersensitivity in rats with chronic constriction injury (CCI) of the sciatic nerve.
2
SCS increased OX-42 immunoreactivity (a marker of microglial activation) in the bilateral dorsal horns of the spinal cord.
3
SCS upregulated the mRNA levels of M1-like microglial markers (iNOS, CD16) and the pro-inflammatory cytokine IL-1b, but did not significantly alter M2-like markers.

Research Summary

The study examined the effects of conventional spinal cord stimulation (SCS) on microglial activation in rats with chronic constriction injury (CCI) of the sciatic nerve, a model of neuropathic pain. The results indicated that SCS transiently reduced mechanical hypersensitivity but also increased microglial activation and M1-like polarization in the spinal cord. Inhibition of microglial activation with minocycline prolonged the pain-relieving effects of SCS, suggesting that modulating microglial activity could improve SCS efficacy.

Practical Implications

Therapeutic Strategies

Combining SCS with adjuvant pharmacotherapy targeting microglial activation may improve and prolong pain relief.

SCS Paradigm Development

Developing new SCS paradigms that better modulate spinal glial function could enhance therapeutic efficacy.

Further Research

Further investigation into the roles of M1- and M2-like polarization markers and associated cytokines in SCS-induced analgesia is warranted.

Study Limitations

1
The study only examined the conventional SCS paradigm; effects of other SCS paradigms (high-frequency, burst SCS) on glial phenotypes remain to be studied.
2
Intermittent SCS was used instead of continuous SCS, which is more common in clinical practice; microglial modulation may differ with different stimulation time schemes.
3
Tissues from CCI rats treated with minocycline and SCS were not harvested for RT-PCR and Western blotting, so the mechanism of improved pain inhibition remains to be confirmed.

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