The Wnt/β-Catenin Pathway Regulated Cytokines for Pathological Neuropathic Pain in Chronic Compression of Dorsal Root Ganglion Model

Neural Plasticity, 2021 · DOI: https://doi.org/10.1155/2021/6680192 · Published: April 19, 2021

Simple Explanation

This research investigates the role of the Wnt/β-catenin pathway in neuropathic pain (NP) caused by chronic compression of the dorsal root ganglion (DRG). The Wnt/β-catenin pathway is involved in various cellular processes, and its activation can lead to the production of inflammatory factors. The study found that compressing the DRG in rats activated the Wnt/β-catenin pathway in the DRG and spinal cord, leading to increased levels of pro-inflammatory cytokines like TNF-α and IL-18. These changes were associated with pain behavior in the rats. When the researchers inhibited the Wnt/β-catenin pathway using a drug called XAV939, the pain was reduced, and the levels of TNF-α and IL-18 decreased. This suggests that the Wnt/β-catenin pathway plays a key role in neuropathic pain and could be a potential target for treatment.

Study Duration

28 days

Participants

59 SD (Sprague Dawley) male rats

Evidence Level

Not specified

Key Findings

1
Chronic compression of the DRG leads to changes in the expression of multiple Wnt pathway-related genes and rapid activation of the Wnt/β-catenin pathway in the DRG and spinal cord.
2
Inhibition of the Wnt/β-catenin pathway alleviates allodynia (pain from a non-painful stimulus) induced by chronic nerve compression, suggesting its role in pain maintenance.
3
Chronic compression elevates the levels of TNF-α and IL-18, which are significantly correlated with pain. Blocking the Wnt/β-catenin pathway decreases the levels of these inflammatory factors.

Research Summary

The study investigates the role of the Wnt/β-catenin pathway in neuropathic pain (NP) induced by chronic compression of the dorsal root ganglion (DRG). The researchers used a rat model to mimic lumbar foraminal stenosis and lumbar disc herniation, common causes of low back pain and NP. The findings reveal that chronic nerve compression activates the Wnt/β-catenin pathway in the DRG and spinal cord, leading to increased levels of pro-inflammatory cytokines TNF-α and IL-18. These cytokines are negatively correlated with mechanical withdrawal thresholds, indicating their involvement in pain. Inhibiting the Wnt/β-catenin pathway with XAV939 alleviated pain and reduced the levels of TNF-α and IL-18, suggesting that the Wnt/β-catenin pathway plays a critical role in the pathogenesis of NP and may be an effective therapeutic target.

Practical Implications

Therapeutic Target Identification

The Wnt/β-catenin pathway could be a potential target for the treatment of neuropathic pain.

Drug Development

Development of drugs targeting the Wnt/β-catenin pathway could lead to new treatments for nerve compression diseases.

Understanding Pain Mechanisms

The study provides insights into the molecular mechanisms underlying neuropathic pain, particularly the role of inflammation and the Wnt/β-catenin pathway.

Study Limitations

1
The study was conducted on rats, and the results may not be directly applicable to humans.
2
The specific mechanisms by which the Wnt/β-catenin pathway induces peripheral and central sensitization were not fully elucidated.
3
Further research is needed to investigate the long-term effects of inhibiting the Wnt/β-catenin pathway.

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