SAFit2 reduces neuroinflammation and ameliorates nerve injury‑induced neuropathic pain

Journal of Neuroinflammation, 2022 · DOI: 10.1186/s12974-022-02615-7 · Published: October 4, 2022

Simple Explanation

Neuropathic pain, resulting from nerve injuries or diseases, has limited effective treatments. This study explores SAFit2, an FKBP51 inhibitor, as a potential treatment for nerve injury-induced neuropathic pain. SAFit2 was found to reduce neuroinflammation and alleviate neuropathic pain in mice with nerve injuries. It works by reducing immune cell infiltration and reducing the production of inflammatory mediators. SAFit2 also desensitizes TRPV1 channels in sensory neurons, reducing the release of pro-inflammatory neuropeptides. These findings suggest SAFit2 as a promising candidate for treating nerve injury-induced neuropathic pain.

Study Duration

21 days

Participants

Male C57Bl/6N mice (8-12 weeks old)

Evidence Level

Level 1, Animal Study

Key Findings

1
SAFit2 ameliorates nerve injury-induced neuropathic pain by reducing neuroinflammation.
2
SAFit2 reduces the infiltration of immune cells into neuronal tissue and reduces NF-κB pathway activation, leading to reduced cytokine and chemokine levels.
3
SAFit2 desensitizes the pain-relevant TRPV1 channel and reduces the release of pro-inflammatory neuropeptides from sensory neurons.

Research Summary

This study investigates the effect of SAFit2 on nerve injury-induced neuropathic pain in mice. The findings indicate that SAFit2 reduces neuroinflammation and ameliorates mechanical hypersensitivity. SAFit2 reduces cytokine and chemokine levels in dorsal root ganglia and spinal cord after nerve injury, indicating a reduction in inflammatory and pain-mediating signals. SAFit2 treatment leads to a reduced infiltration of immune cells into DRGs and spinal cord and desensitizes the TRPV1 channel in sensory neurons, reducing CGRP secretion.

Practical Implications

Therapeutic Potential

SAFit2 represents a novel and promising drug candidate for the treatment of nerve injury-induced neuropathic pain.

Targeting Neuroinflammation

SAFit2's ability to reduce neuroinflammation suggests potential for treating other conditions involving neuroinflammation.

Combined Action

The dual action of SAFit2 on both immune cells and sensory neurons makes it a potent therapeutic agent for neuropathic pain.

Study Limitations

1
Lack of female mice in behavioral assays.
2
SAFit2 interferes rather in the maintenance of neuropathic pain than in its onset
3
The mechanical hypersensitivity of the SNI-treated animals is not completely restored to baseline levels

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