Temporal Transcriptomic Changes in the Cingulate Cortex of Neuropathic Pain Mice

Area of Science:

• Neuroscience
• Molecular Biology
• Genomics

Background:

• Neuropathic pain (NP) is a severe condition with inadequate treatments.
• The cingulate cortex is vital for pain perception, but its molecular changes in NP are not fully understood.

Purpose of the Study:

• To comprehensively map the spatiotemporal transcriptomic alterations in the cingulate cortex during neuropathic pain.
• To identify key molecular pathways and genes involved in NP pathogenesis within the anterior cingulate cortex (ACC) and midcingulate cortex (MCC).

Main Methods:

• RNA sequencing was performed on mouse ACC and MCC at 2 and 4 weeks post-spared nerve injury.
• Bioinformatics analyses included differential gene expression, functional enrichment, weighted gene co-expression network analysis, and protein-protein interaction network construction.

Main Results:

• Significant, time-dependent transcriptomic dysregulation was observed in both ACC and MCC, with increasing gene alterations over time.
• Key pathways implicated in NP pathogenesis include synaptic plasticity, neuroinflammation, neurodegeneration, and mitochondrial dysfunction.
• The ACC showed broader pathway alterations than the MCC, with distinct early (neuroinflammation) and late (mitochondrial dysfunction/neurodegeneration) phase changes.

Conclusions:

• This study provides a detailed transcriptomic atlas of the cingulate cortex in NP.
• Findings reinforce the roles of synaptic and neuroinflammatory mechanisms and suggest mitochondrial dysfunction in NP.
• The results offer a foundation for further mechanistic investigations into NP treatment strategies.