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Drp1/HK1/NLRP3-Associated Pathway Contributes to Neuronal Pyroptosis-Related Signaling in Neuropathic Pain
Pinying Wang1, Jialing Chen1,2, Bohan Zhang3
1Department of Pain, Heping District, The First Hospital of China Medical University, No. 155, Nanjing North Street, Shenyang, 110001, China.
Molecular Neurobiology
|August 3, 2026
Summary
Neuropathic pain involves pyroptosis, a cell death process. This study found that targeting the Drp1/HK1/NLRP3 pathway in neurons can reduce pyroptosis and alleviate pain in a mouse model.
Area of Science:
- Neuroscience
- Cell Biology
- Pain Research
Background:
- Neuropathic pain (NP) is a chronic pain condition affecting the nervous system.
- Pyroptosis, a form of inflammatory cell death, is increasingly implicated in NP pathogenesis.
- Understanding the molecular mechanisms of NP is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of NLRP3-mediated pyroptosis in neuropathic pain.
- To explore the regulation of neuronal pyroptosis by HK1 and Drp1 in NP.
- To identify potential therapeutic targets for neuropathic pain.
Main Methods:
- A spared nerve injury (SNI) mouse model was used to induce neuropathic pain.
- Assessed pain hypersensitivity using von Frey filaments and the hot plate test.
- Analyzed spinal cord tissues using Western blot, immunofluorescence, and electron microscopy.
- Investigated the function of HK1 and Drp1 via viral vectors and siRNA.
Main Results:
- SNI induced persistent pain hypersensitivity and neuronal alterations.
- Upregulation of pyroptosis markers (NLRP3, ASC, GSDMD-N, IL-1β) and neuronal pyroptosis signals were observed.
- HK1 expression decreased while Drp1 expression increased in neurons post-SNI.
- Restoring HK1 or inhibiting Drp1 alleviated pain and suppressed pyroptosis.
- Mitochondrial analysis showed reduced HK1 and increased Drp1.
Conclusions:
- Drp1 upregulation is linked to HK1 downregulation and NLRP3-mediated neuronal pyroptosis in NP.
- The Drp1/HK1/NLRP3 pathway is a key regulator of neuronal pyroptosis in neuropathic pain.
- This pathway represents a potential therapeutic target for managing neuropathic pain.
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