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The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice
Published on: July 16, 2014
STING Modulating ER-Phagy in the Prelimbic Cortex Neurons Contributed to Neuropathic Pain and Emotional Comorbidity
Yongda Liu1,2, Xu Yang1, Shihui Kuai1
1Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, China.
CNS Neuroscience & Therapeutics
|June 23, 2026
Summary
Enhanced endoplasmic reticulum-phagy (ER-phagy) in prefrontal cortex (PrL) neurons alleviates neuropathic pain and associated emotional dysfunction by modulating the STING pathway. This study reveals ER-phagy as a potential therapeutic target for pain and mood disorders.
Area of Science:
- Neuroscience
- Molecular Biology
- Pain Research
Background:
- Autophagy is implicated in neuropathic pain, but the role of STING (stimulator of interferon genes) in prefrontal cortex (PrL) neurons remains unclear.
- The interplay between STING, endoplasmic reticulum (ER)-phagy, and neuropathic pain in PrL neurons is not fully understood.
- Previous data suggest autophagy's crucial role in neuropathic pain, with STING potentially having paradoxical effects on pain and emotions.
Purpose of the Study:
- To investigate the role of ER-phagy in the PrL on neuropathic pain.
- To explore whether STING and its pathway are targets for ER-phagy in the pain process.
- To examine the effects of modulating ER-phagy and STING on pain and emotional behaviors in a neuropathic pain model.
Main Methods:
- Administered drugs (4-phenylbutyric acid, tunicamycin, 3-methyladenine, rapamycin) to assess ER stress and autophagy in the PrL of spinal nerve ligation (SNL) mice.
- Utilized adeno-associated virus (AAV) injections to investigate ER-phagy's modulation of pain and emotional behaviors.
- Modulated the cGAS/STING pathway using 2'3-cGAMP and RU521, and altered STING expression via PrL AAV injections to study its interaction with ER-phagy markers like LC3.
Main Results:
- ER-phagy in the PrL alleviated SNL-induced ER stress via the cGAS/STING pathway.
- Modulating ER-phagy and STING in PrL neurons significantly altered pain and emotion-related behaviors.
- Identified a binding interaction between STING and LC3 in PrL neurons, highlighting a novel target for ER-phagy.
Conclusions:
- Enhanced ER-phagy in PrL neurons exerts analgesic, anti-anxiety, and antidepressant effects in SNL mice.
- Modulating STING is a key mechanism through which ER-phagy influences pain and emotional comorbidity.
- Targeting PrL ER-phagy offers a potential therapeutic strategy for neuropathic pain and associated emotional disorders.
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