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Updated: Jan 3, 2026
Modified Spared Nerve Injury Surgery Model of Neuropathic Pain in Mice
Published on: January 25, 2022
MiR-15a attenuates peripheral nerve injury-induced neuropathic pain by targeting AKT3 to regulate autophagy
Longxue Cai1, Xianfa Liu2, Qicai Guo2
1Department of Emergency, First Affiliated Hospital of Gannan Medical University, No. 23, Qingnian Road, Zhanggong District, Ganzhou, Jiangxi, China. LongxueCaisdf@163.com.
Objective:
Aim of this study was to detect the expression of miR-15a in rats following chronic constriction injury (CCI) and to investigate the regulatory functions of miR-15a during neuropathic pain (NP) development.
Methods:
CCI was performed in adult Sprague-Dawley rats to set up the rat model of neuropathic pain. MiR-15a agomir and scrambled control were delivered into the implanted catheter of rats. The mechanical allodynia and thermal hyperalgesia were assessed in both CCI- and sham-operated groups. Rat lumbar spinal cord tissues were harvested for mRNA and protein analyses. The primary spinal microglia were isolated from adult Sprague-Dawley rats and transfected with miR-15a mimics, scramble miRNA, miR-15a inhibitor or its corresponding negative control. Cell lysates were collected for mRNA and protein analyses.
Results:
Compared to sham-operated group, the expression of miR-15a in CCI rats was significantly reduced, whereas neuroinflammation in spinal cord tissues was increased. Intrathecal administration of miR-15a agomir significantly attenuated CCI-induced NP and the levels of proinflammatory cytokines, including IL-6, IL-1β, and TNF-α. AKT3 was predicted and confirmed as a miR-15a-regulated gene. We further demonstrated that miR-15a overexpression downregulated the level of AKT3 in primary rat microglia and rat CCI model. Moreover, the upregulation of miR-15a induced the expressions of autophagy-associated proteins, suggesting that the regulation mechanism of miR-15a in NP development involves AKT3-mediated autophagy via inhibiting the expression of AKT3.
Conclusion:
Our findings indicated that miR-15a might serve as a promising therapeutic target for the management of NP through the stimulation of autophagic process.
Insights
MicroRNA-15a (miR-15a) is downregulated in neuropathic pain (NP) and its restoration alleviates pain by modulating AKT3-mediated autophagy. This suggests miR-15a is a potential therapeutic target for NP management.
Area of Science:
- Neuroscience
- Molecular Biology
- Pain Research
Background:
- Neuropathic pain (NP) is a debilitating condition often associated with chronic constriction injury (CCI).
- The role of microRNAs (miRNAs) in the development and progression of NP is an area of active investigation.
- Specific molecular mechanisms underlying NP, including neuroinflammation and altered gene expression, require further elucidation.
Purpose of the Study:
- To investigate the expression levels of microRNA-15a (miR-15a) in a rat model of neuropathic pain induced by chronic constriction injury (CCI).
- To explore the functional role of miR-15a in the development of neuropathic pain.
- To identify the molecular targets and pathways regulated by miR-15a in the context of NP.
Main Methods:
- Establishment of a rat model of neuropathic pain using chronic constriction injury (CCI).
- Intrathecal administration of miR-15a agomir or control to assess its effect on pain behaviors and neuroinflammation.
- Analysis of miR-15a expression, pro-inflammatory cytokine levels (IL-6, IL-1β, TNF-α), and AKT3 expression in spinal cord tissues and primary microglia.
- Investigation of autophagy-associated protein expression.
Main Results:
- miR-15a expression was significantly reduced in CCI rats compared to sham-operated controls, correlating with increased spinal neuroinflammation.
- Intrathecal administration of miR-15a agomir attenuated mechanical allodynia and thermal hyperalgesia in CCI rats, reducing pro-inflammatory cytokine levels.
- AKT3 was identified as a direct target of miR-15a, with miR-15a overexpression downregulating AKT3 levels.
- Upregulation of miR-15a promoted the expression of autophagy-associated proteins, indicating AKT3-mediated autophagy.
Conclusions:
- miR-15a plays a crucial role in the development of neuropathic pain.
- The therapeutic potential of miR-15a in managing NP lies in its ability to inhibit AKT3 expression and promote autophagy.
- Stimulating the autophagic process via miR-15a represents a promising therapeutic strategy for neuropathic pain.
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