Astrocyte senescence‑like response related to peripheral nerve injury‑induced neuropathic pain

Cellular & Molecular Biology Letters, 2023 · DOI: https://doi.org/10.1186/s11658-023-00474-5 · Published: September 7, 2023

Aging Immunology Pain Management

Simple Explanation

Peripheral nerve damage can lead to neuroinflammation, which contributes to neuropathic pain. This study explores the connection between astrocyte senescence and neuropathic pain following chronic sciatic nerve injury in rats. The researchers induced chronic constrictive injury (CCI) to the sciatic nerve in rats to mimic neuropathic pain. They then treated the rats with a senolytic drug combination of dasatinib and quercetin. The study found that the senolytic drug combination attenuated spinal neuroinflammation and mitigated pain hypersensitivities in the rats. This suggests that targeting astrocyte senescence could be a potential therapeutic strategy for neuropathic pain.

Study Duration

14 Days

Participants

36 Sprague–Dawley rats

Evidence Level

Not specified

Key Findings

1
Sciatic nerve CCI in rats resulted in reduced paw mechanical withdrawal threshold (PMWT) and paw thermal withdrawal latency (PTWL), indicating pain hypersensitivity.
2
CCI also led to increased levels of spinal proinflammatory factors and an enhanced degree of senescence in spinal astrocytes.
3
Treatment with dasatinib and quercetin attenuated spinal neuroinflammation and mitigated pain hypersensitivities.

Research Summary

This study investigates the role of astrocyte senescence in neuroinflammation and neuropathic pain (NeP) following peripheral nerve injury (PNI). The findings suggest that PNI induces a senescence-like response in spinal astrocytes, contributing to neuroinflammation and pain hypersensitivity. Targeting astrocyte senescence with senolytic drugs like dasatinib and quercetin may offer a novel therapeutic strategy for treating NeP.

Practical Implications

Therapeutic Target

Astrocyte senescence could be a novel therapeutic target for neuropathic pain.

Senolytic Drugs

Senolytic drugs like dasatinib and quercetin may alleviate neuropathic pain by reducing astrocyte senescence and neuroinflammation.

Biomarker Identification

Clusterin (CLU) identified as potential target for the development of drugs to inhibit astrocyte senescence in neuroinflammation following peripheral nerve injury.

Study Limitations

1
The study was conducted on rats, and the results may not be directly applicable to humans.
2
The exact mechanisms by which astrocyte senescence contributes to neuroinflammation and neuropathic pain need further investigation.
3
The long-term effects and potential side effects of senolytic drug treatment require further evaluation.

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