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Updated: Apr 18, 2026
Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies
Published on: October 6, 2022
Targeting the PDK1/c-Myc/SOX10 Signaling in Oligodendrocytes Alleviates Neuropathic Pain
Pingping Qiao1,2, Lifang Guo3, Guochao Yang1
1State Key Laboratory of Pharmaceutical Biotechnology, Department of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, Medical School, Nanjing University, Nanjing, China.
Oligodendrocyte homeostasis, crucial for nerve insulation, is impaired in neuropathic pain (NPP). Targeting the c-Myc/SOX10 pathway in oligodendrocytes offers a novel therapeutic strategy for NPP.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Neuropathic pain (NPP) presents a significant clinical challenge with few effective treatments.
- The role of oligodendrocyte (OL) homeostasis in NPP pathogenesis remains largely unexplored, despite extensive research on neuronal mechanisms.
Purpose of the Study:
- To investigate the contribution of oligodendrocyte homeostasis to neuropathic pain.
- To identify molecular mechanisms linking oligodendrocyte dysfunction to neuropathic pain.
- To explore potential therapeutic targets for neuropathic pain.
Main Methods:
- Inducible oligodendrocyte lineage-specific Pdk1 conditional knockout (Pdk1 cKO) mice were utilized.
- Chronic constriction injury (CCI) model was employed to induce neuropathic pain.
- RNA sequencing (RNA-seq), morphological, and molecular analyses were performed.
Main Results:
- CCI induced demyelination and reduced PDK1 expression in the CNS.
- Pdk1 cKO mice exhibited mechanical allodynia and thermal hyperalgesia, mirroring CCI-induced NPP.
- PDK1 deficiency impaired myelination through the c-Myc/SOX10 pathway.
Conclusions:
- PDK1-mediated oligodendrocyte homeostasis is a critical factor in neuropathic pain development.
- Modulating the c-Myc pathway presents a promising therapeutic avenue for neuropathic pain.
- Restoring myelin integrity via pharmacological or genetic interventions alleviates neuropathic pain symptoms.
