The Up-regulation of TNF-α Maintains Trigeminal Neuralgia by Modulating MAPKs Phosphorylation and BKCa Channels in Trigeminal Nucleus Caudalis

Frontiers in Cellular Neuroscience, 2021 · DOI: 10.3389/fncel.2021.764141 · Published: November 25, 2021

Simple Explanation

Trigeminal neuralgia (TN) is a severe chronic neuropathic pain, and current treatments are not always effective. This study explores the role of TNF-α, an inflammatory cytokine, in the trigeminal nucleus caudalis (TNC), a key area for processing facial pain. The research investigates how TNF-α affects the phosphorylation of MAPKs (proteins involved in cell signaling) and BKCa channels (which regulate neuron excitability) in the TNC. The findings suggest that increased TNF-α in the TNC leads to increased MAPKs phosphorylation, which negatively regulates BKCa channels, ultimately contributing to TN.

Study Duration

Not specified

Participants

Male Sprague-Dawley rats weighing 200–250 g

Evidence Level

Not specified

Key Findings

1
TNF-α, CCL2, and CXCL1 are significantly increased in the TNC region of ION-CCI rats, suggesting their involvement in trigeminal neuralgia.
2
Exogenous TNF-α reduces the facial mechanical pain threshold and promotes CCL2 expression in the TNC, mimicking the effects of ION-CCI.
3
Inhibitors of MAPKs (ERK, p38, and JNK) can reverse facial mechanical allodynia in ION-CCI rats, indicating the role of MAPKs in TN.

Research Summary

This study investigates the role of TNF-α in trigeminal neuralgia (TN) by examining its effects on MAPKs phosphorylation and BKCa channels in the trigeminal nucleus caudalis (TNC). The results show that TNF-α is upregulated in the TNC region of ION-CCI rats and that exogenous TNF-α can induce similar pain responses. MAPKs phosphorylation is also increased in the TNC of ION-CCI rats. The study suggests that TNF-α increases MAPKs phosphorylation, leading to negative regulation of BKCa channels, contributing to TN. Inhibiting ERK and p38 can reverse the effects of TNF-α on BKCa currents.

Practical Implications

Therapeutic Target Identification

Targeting TNF-α and MAPKs phosphorylation pathways in the TNC could provide novel therapeutic strategies for managing trigeminal neuralgia.

Drug Development

Developing drugs that modulate BKCa channel activity or inhibit TNF-α signaling could offer new avenues for pain relief in TN patients.

Personalized Medicine

Understanding the specific roles of different MAPKs (ERK, p38, JNK) in TN may allow for more targeted and personalized treatment approaches.

Study Limitations

1
The study is limited to an animal model (rats), and the findings may not directly translate to human TN.
2
The exact mechanisms by which TNF-α modulates MAPKs phosphorylation and BKCa channels require further investigation.
3
The study focuses primarily on the TNC region, and the contributions of other brain regions to TN were not explored.

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