NaHS modulates astrocytic EAAT2 expression to impact SNI-induced neuropathic pain and depressive-like behaviors

Scientific Reports, 2025 · DOI: https://doi.org/10.1038/s41598-025-86885-0 · Published: January 14, 2025

Simple Explanation

This study explores how hydrogen sulfide (H2S) affects neuropathic pain, focusing on the role of astrocytes and glutamate, a brain chemical. They used a nerve injury model in mice. The research found that sodium hydrosulfide (NaHS), which releases H2S, can improve pain thresholds in mice with nerve injury. It also lowers glutamate levels in the spinal cord. These findings suggest a new way to treat neuropathic pain by targeting astrocytes and a protein called EAAT2, which helps regulate glutamate.

Study Duration

14 days

Participants

102 adult male C57BL/6 mice

Evidence Level

Not specified

Key Findings

1
SNI induces chronic pain and depressive-like behaviors in mice, evidenced by decreased mechanical pain threshold, thermal pain latency, and reduced exploratory behavior.
2
SNI leads to abnormal activation of spinal astrocytes and glutamate accumulation, indicating a dysfunction in normal astrocyte functions.
3
NaHS treatment alleviates SNI-induced pain hypersensitivity and depression-like behavior, potentially through enhanced EAAT2 expression in astrocytes.

Research Summary

This study investigates the therapeutic effect of NaHS on neuropathic pain using the spared nerve injury (SNI) model in mice, focusing on astrocytes and glutamate. The findings reveal that NaHS enhances pain thresholds, reduces glutamate levels in the spinal cord, and decreases neuronal discharge frequency in the S1HL brain area. The study demonstrates that NaHS treatment alleviates central sensitization and depression-like behavior by increasing the expression of EAAT2 in astrocytes.

Practical Implications

Therapeutic Potential

H2S donors like NaHS may offer a novel therapeutic approach for treating neuropathic pain by modulating astrocyte function and EAAT2 expression.

Targeted Treatment

Focusing on astrocyte activation and EAAT2 regulation could provide more effective strategies for managing chronic pain and associated mood disorders.

Clinical Applications

Developing safer and more efficient H2S donors is crucial for advancing the clinical application of H2S-based therapies for neuropathic pain.

Study Limitations

1
Whether the intraperitoneal injection method used in this study affects pain sensitivity remains unknown.
2
The study only investigated one-time points for NaHS administration, and further research will explore more suitable treatment windows.
3
The specific mechanism by which H2S regulates astrocytes is unclear.

Your Feedback

Was this summary helpful?

Back to Physiology