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The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice
Published on: July 16, 2014
MicroRNA-142-3p relieves neuropathic pain by targeting high mobility group box 1
Yang Zhang1, Junying Mou2, Li Cao3
1Department of Anesthesiology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China.
Abstract:
MicroRNA (miRNA) are emerging as critical regulators of neuropathic pain development. Neuroinflammation contributes to the development of neuropathic pain. miR‑142‑3p has been characterized as an inflammation‑related miRNA in various pathological processes. However, little is known about the role of miR‑142‑3p in neuroinflammation and neuropathic pain. The present study aimed to investigate the function of miR‑142‑3p in neuropathic pain by creating a murine model using spinal nerve ligation (SNL). A significant reduction in miR‑142‑3p expression was observed in the dorsal root ganglion of mice with SNL (P<0.05) compared with control mice. Overexpression of miR‑142‑3p significantly inhibited neuropathic pain and neuroinflammation in mice with SNL (P<0.05). High mobility group box 1 (HMGB1) was identified as a direct target gene of miR‑142‑3p by bioinformatic analysis and dual‑luciferase reporter assays. Overexpression of miR‑142‑3p significantly reduced the mRNA and protein expression levels of HMGB1 in vitro and in vivo (P<0.05). In addition, HMGB1 mRNA expression and miR‑142‑3p expression were inversely correlated in mice with SNL. Furthermore, overexpression of HMGB1 significantly reversed the inhibitory effect of miR‑142‑3p on neuroinflammation and neuropathic pain development (P<0.05). Overall, these results suggest that miR‑142‑3p functions as a negative regulator of neuropathic pain development through the downregulation of HMGB1, indicating that miR‑142‑3p may serve as a potential therapeutic target for neuropathic pain.
Insights
MicroRNA-142-3p (miR-142-3p) reduces neuropathic pain and neuroinflammation by targeting High mobility group box 1 (HMGB1). This study shows miR-142-3p is a potential therapeutic target for neuropathic pain.
Area of Science:
- Neuroscience
- Molecular Biology
- Pain Research
Background:
- MicroRNAs (miRNAs) are key regulators in neuropathic pain development.
- Neuroinflammation is a significant factor in neuropathic pain.
- miR-142-3p is linked to inflammation but its role in neuropathic pain is unclear.
Purpose of the Study:
- To investigate the function of miR-142-3p in neuropathic pain and neuroinflammation.
- To explore the underlying molecular mechanisms involving High mobility group box 1 (HMGB1).
Main Methods:
- A murine model of neuropathic pain was established using spinal nerve ligation (SNL).
- miR-142-3p expression levels were measured in the dorsal root ganglion.
- The relationship between miR-142-3p, HMGB1, neuroinflammation, and pain was assessed using molecular and behavioral techniques, including bioinformatic analysis and dual-luciferase reporter assays.
Main Results:
- miR-142-3p expression was significantly reduced in mice with SNL.
- Overexpression of miR-142-3p alleviated neuropathic pain and neuroinflammation.
- HMGB1 was identified as a direct target of miR-142-3p, with its expression inversely correlated to miR-142-3p levels.
- HMGB1 overexpression counteracted the protective effects of miR-142-3p.
Conclusions:
- miR-142-3p acts as a negative regulator in neuropathic pain development by downregulating HMGB1.
- miR-142-3p presents a potential therapeutic target for managing neuropathic pain and associated neuroinflammation.
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