RNA interference‑mediated silencing of DNA methyltransferase 1 attenuates neuropathic pain by accelerating microglia M2 polarization

BMC Neurology, 2022 · DOI: https://doi.org/10.1186/s12883-022-02860-6 · Published: January 1, 2022

Simple Explanation

Neuropathic pain (NP) is pain resulting from a disease or lesion affecting the somatosensory nervous system, and its pathogenesis is not completely understood. Microglia, as the main innate immune cell in the CNS, play a vital role in NP development. This study explores how silencing a gene called DNMT1, which is involved in DNA methylation, can reduce neuropathic pain by changing the behavior of microglia. The researchers used a rat model of neuropathic pain called chronic constriction injury (CCI). They found that by reducing the activity of DNMT1 using RNA interference, they could shift microglia from an inflammatory state (M1) to an anti-inflammatory state (M2). This shift reduced pain. The study also found that DNMT1 affects the PI3K/Akt pathway, which is involved in inflammation. Silencing DNMT1 blocks the PI3K/Akt pathway, further promoting the shift of microglia to the M2 state and reducing neuropathic pain. This suggests that targeting DNMT1 could be a potential treatment for neuropathic pain.

Study Duration

Not specified

Participants

32 Sprague–Dawley healthy male rats

Evidence Level

Level II: Experimental study in rats

Key Findings

1
DNMT1 was upregulated in microglia of CCI rats, suggesting its involvement in neuropathic pain.
2
DNMT1 siRNA alleviated CCI-induced NP, as evidenced by increased pain thresholds (MWT and TWL) and reduced pro-inflammatory cytokines.
3
DNMT1 siRNA promoted microglia M2 polarization in CCI rats by decreasing M1 markers and increasing M2 markers.

Research Summary

This study investigates the role of DNMT1 in neuropathic pain (NP) and explores the potential of RNA interference-mediated DNMT1 silencing to alleviate CCI-induced NP in rats. The study demonstrates that DNMT1 silencing promotes microglia M2 polarization and reduces inflammation by blocking the PI3K/Akt pathway, leading to the attenuation of NP. The findings suggest that targeting DNMT1 could be a promising therapeutic strategy for NP treatment.

Practical Implications

Therapeutic Target

DNMT1 is identified as a potential therapeutic target for neuropathic pain.

Treatment Strategy

RNA interference-mediated DNMT1 silencing could be a novel treatment strategy for neuropathic pain.

Pathway Modulation

Modulating the PI3K/Akt pathway through DNMT1 silencing can alleviate neuropathic pain.

Study Limitations

1
The study lacks in-depth studies on the function of DNMT1 knockdown on the PI3K/Akt pathway.
2
The markers of microglia M1 and M2 polarization were only detected at one time point.
3
The study did not explore the downstream microRNAs of DNMT1 involved in modulating M2 polarization of microglia.

Your Feedback

Was this summary helpful?

Back to Neurology