Circular RNA SMEK1 promotes neuropathic pain in rats through targeting microRNA-216a-5p to mediate Thioredoxin Interacting Protein (TXNIP) expression

BIOENGINEERED, 2021 · DOI: https://doi.org/10.1080/21655979.2021.1965811 · Published: August 4, 2021

Simple Explanation

Neuropathic pain (NP) is a condition caused by damage to the nervous system. This study investigated the role of circSMEK1 in NP using rat and cell models. The study found that circSMEK1 and TXNIP were increased in NP, while miR-216a-5p was decreased. Reducing circSMEK1 or increasing miR-216a-5p lessened pain and inflammation in the rats. The experiments showed that circSMEK1 controls TXNIP by interacting with miR-216a-5p. This interaction affects inflammation and microglia polarization, which are important in NP.

Study Duration

Not specified

Participants

84 adult male SD rats

Evidence Level

Level 5: Animal study

Key Findings

1
CircSMEK1 and TXNIP are upregulated in neuropathic pain (NP), while miR-216a-5p is downregulated.
2
Knockdown of circSMEK1 or elevation of miR-216a-5p reduces inflammatory cytokines and microglia activation, promoting anti-inflammatory microglia polarization.
3
CircSMEK1 facilitates NP inflammation and microglia M1 polarization by modulating the miR-216a-5p/TXNIP axis.

Research Summary

This study investigates the role of circSMEK1 in neuropathic pain (NP) using rat and cell models. The results indicate that circSMEK1 and TXNIP are upregulated in NP, while miR-216a-5p is downregulated. Knockdown of circSMEK1 or elevation of miR-216a-5p alleviates pain and reduces inflammatory cytokines in the spinal cord, while upregulation of circSMEK1 or knockdown of miR-216a-5p has the opposite effect. Mechanistically, circSMEK1 mediates TXNIP expression through competitive adsorption of miR-216a-5p, facilitating NP inflammation and microglia M1 polarization. This provides a potential therapeutic target for NP treatment.

Practical Implications

Therapeutic Target

CircSMEK1/miR-216a-5p/TXNIP axis represents a novel therapeutic target for neuropathic pain.

Microglia Polarization

Modulating circSMEK1 expression may influence microglia polarization, shifting the balance from pro-inflammatory (M1) to anti-inflammatory (M2) phenotypes, potentially alleviating neuropathic pain.

Inflammation Reduction

Targeting circSMEK1 could reduce the levels of inflammatory cytokines (TNF-α, IL-1β, IL-6) in the spinal cord, thereby reducing neuroinflammation and neuropathic pain.

Study Limitations

1
The study is limited to rat models and in vitro cell cultures.
2
Further studies are needed to validate these findings in human subjects.
3
The long-term effects of modulating circSMEK1 expression on neuropathic pain were not assessed.

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