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Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies
Published on: October 6, 2022
MiR-150 alleviates neuropathic pain via inhibiting toll-like receptor 5
Li-Juan Ji1, Jing Shi2, Jing-Min Lu3
1Department of Sport Medicine and Rehabilitation Center, School of Kinesiology, Shanghai University of Sport, Shanghai, China.
Abstract:
MicroRNAs (miRNAs) are reported as vital participators in the pathophysiological course of neuropathic pain. However, the underlying mechanisms of the functional roles of miRNAs in neuropathic pain are largely unknown. This study was designed to explore the potential role of miR-150 in regulating the process of neuropathic pain in a rat model established by chronic sciatic nerve injury (CCI). Overexpression of miR-150 greatly alleviated neuropathic pain development and reduced inflammatory cytokine expression, including COX-2, interleukin IL-6, and tumor necrosis factor (TNF)-α in CCI rats. By bioinformatic analysis, 3'-untranslated region (UTR) of Toll-like receptor (TLR5) was predicted to be a target of miR-150. TLR5 commonly serves as an important regulator of inflammation. Overexpression of miR-150 significantly suppressed the expression of TLR5 in vitro and in vivo. Furthermore, upregulation of TLR5 decreased the miR-150 expression and downregulation of TLR5 increased miR-150, respectively. Overexpression of TLR5 significantly reversed the miR-150-induced suppressive effects on neuropathic pain. In conclusion, our current study indicates that miR-150 may inhibit neuropathic pain development of CCI rats through inhibiting TLR5-mediated neuroinflammation. Our findings suggest that miR-150 may provide a novel therapeutic target for neuropathic pain treatment.
Insights
MicroRNA-150 (miR-150) alleviates neuropathic pain by reducing inflammation. It targets Toll-like receptor 5 (TLR5), suggesting miR-150 as a potential therapeutic target for pain management.
Area of Science:
- Neuroscience
- Molecular Biology
- Pain Research
Background:
- MicroRNAs (miRNAs) play roles in neuropathic pain, but mechanisms remain unclear.
- Neuropathic pain, often resulting from nerve injury, involves complex inflammatory processes.
Purpose of the Study:
- To investigate the role of miR-150 in neuropathic pain.
- To explore the regulatory mechanism of miR-150 in chronic sciatic nerve injury (CCI) rat models.
Main Methods:
- Established a rat model of neuropathic pain via chronic sciatic nerve injury (CCI).
- Overexpressed miR-150 and assessed its effects on pain behaviors and inflammatory markers (COX-2, IL-6, TNF-α).
- Utilized bioinformatic analysis to identify miR-150 targets, predicting Toll-like receptor 5 (TLR5).
- Validated the interaction between miR-150 and TLR5 in vitro and in vivo.
- Investigated the effect of TLR5 manipulation on miR-150 expression and pain.
Main Results:
- Overexpression of miR-150 significantly reduced neuropathic pain and inflammatory cytokine levels in CCI rats.
- Bioinformatic analysis identified TLR5 as a target of miR-150.
- miR-150 overexpression suppressed TLR5 expression, while TLR5 upregulation decreased miR-150 levels.
- Overexpression of TLR5 reversed the pain-alleviating effects of miR-150.
Conclusions:
- miR-150 inhibits neuropathic pain development in CCI rats by suppressing TLR5-mediated neuroinflammation.
- miR-150 represents a potential novel therapeutic target for neuropathic pain treatment.

