Background & Aims
The streptozotocin (STZ)-induced diabetic mice are commonly used as animal models to study diabetic neuropathic pain (DNP) and potential pain therapies. However, the expression changes of the GABAergic system and the function of its transcription factor (TF) in PDN are not well understood. In this study, we confirmed the increase in mechanical and thermal pain hypersensitivity in the STZ-induced diabetic mice model. These findings suggest that overexpression of Ascl1 and lhx6 may alleviate neuropathic pain in STZ-induced diabetic mice by modulating multiple intracellular signaling via upregulation of the GABAergic neuronal function.
Methods
1. Reagents
2. Animals
3. Lentivirus vector generation and intrathecal injection
4. Diabetes induction
5. Determination of diabetes-induced neuropathic pain
6. Mouse DRG Neuron Cultures
7. RNA purification, cDNA synthesis, and RNA seq analysis
8. Real-time PCR
9. Patch clamp
10. Statistics
Results
1. Identification of expression changes in various pain-related genes through RNA seq analysis in DRG of diabetic mice
2. mRNA relative expression level of GABAergic system-related genes and transcription factors in DRG of diabetic mice
3. Effect of Intrathecal injection of Ascl1 and Lhx6 on the mechanical allodynia and heat hyperalgesia in diabetic mice
4. Effect of Ascl1 and Lhx6 on the expression level of pain-related genes in DRG of diabetic mice
5. Effect of Ascl1 and Lhx6 on neuronal hyperexcitability in the DRG of diabetic mice in vivo
6. The identification of target genes related to the function of the GABAergic system by overexpression of Ascl1 and Lhx6
Conclusions
we summarized the role of specific Ascl1 and Lhx6 in the periphery of diabetic mice and conducted the transcriptome analysis of gene changes and key pathways using RNA seq. We identified several DEGs and pathways that may be involved in the pain mechanism of STZ-induced diabetic mice. We found that the A/L-expressing STZ group are important regulators of diabetic neuropathic pain, as they not only upregulate GABAergic function but also affect pain-related genes, which attenuate pain induction.
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Presenting Author
Sung-Min Hwang
Poster Authors
Topics
- Models: Chronic Pain - Neuropathic