Disruption of C/EBPβ‑Clec7a axis exacerbates neuroinflammatory injury via NLRP3 inflammasome‑mediated pyroptosis in experimental neuropathic pain

Journal of Translational Medicine, 2022 · DOI: https://doi.org/10.1186/s12967-022-03779-9 · Published: November 17, 2022

Immunology Pain Management

Simple Explanation

Neuropathic pain is a complex chronic pain condition resulting from nervous system damage or disease, often involving neuroinflammation along pain pathways. Pyroptosis, a novel type of regulated cell death, has been observed in damaged neurocytes associated with neuropathic pain, suggesting its significant contribution to the pathology. This study uses microarray and RNA sequencing to understand gene expression patterns in a rat model of neuropathic pain, identifying potential therapeutic targets.

Study Duration

Not specified

Participants

210 adult male Sprague–Dawley rats

Evidence Level

Not specified

Key Findings

1
Clec7a is significantly upregulated in spinal cord tissues of rats with chronic constriction injury (CCI), a model for neuropathic pain.
2
Knockdown of Clec7a markedly attenuated CCI-induced mechanical allodynia and reduced the release of pro-inflammatory cytokines.
3
C/EBPβ knockdown significantly suppressed CCI- or LPS/ATP-induced Clec7a upregulation, subsequently reducing pyroptosis.

Research Summary

The study reveals a novel role of the C/EBPβ-Clec7a axis in neuropathic pain progression, indicating that CCI-induced overexpression of Clec7a and the direct interaction between C/EBPβ and Clec7a along pain pathways may contribute to neuropathic pain. It supports the idea that this axis triggers the phosphorylation of Syk, ERK and JNK proteins, as well as activating NLRP3 inflammasome-mediated pyroptosis. The preclinical investigation suggests the C/EBPβ-Clec7a axis as a potential target for alleviating neuropathic pain by reducing neuroinflammation, offering a promising clinical approach.

Practical Implications

Therapeutic Target

The C/EBPβ-Clec7a axis could be a promising therapeutic target for the treatment of neuropathic pain.

Neuroinflammation Reduction

Targeting this axis may alleviate neuropathic pain through reducing neuroinflammation.

Clinical Translation

This research paves the way for clinical translation of new therapies for neuropathic pain.

Study Limitations

1
The study is pre-clinical, and findings need to be validated in human clinical trials.
2
The precise mechanisms underlying the interaction between C/EBPβ and Clec7a require further investigation.
3
The long-term effects of targeting the C/EBPβ-Clec7a axis on neuropathic pain need to be evaluated.

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