Hyperbaric Oxygen Therapy Alleviates Paclitaxel-Induced Peripheral Neuropathy Involving Suppressing TLR4-MyD88-NF-κB Signaling Pathway

Int. J. Mol. Sci., 2023 · DOI: 10.3390/ijms24065379 · Published: March 11, 2023

Simple Explanation

Paclitaxel, a chemotherapy drug, often causes peripheral neuropathy, leading to pain and reduced quality of life. This study investigates how hyperbaric oxygen therapy (HBOT) can alleviate this neuropathy by affecting specific molecular pathways. The study focuses on the TLR4-MyD88-NF-κB pathway, which is involved in inflammation and pain signaling in the nervous system. Researchers used a rat model of paclitaxel-induced neuropathy to test the effects of HBOT, along with a TLR4 agonist (LPS) and antagonist (TAK-242). The results suggest that HBOT can alleviate CIPN by modulating the TLR4-MyD88-NF-κB pathway. HBOT had no superior efficacy to TAK-242 alone and the TAK-242/HBOT group, suggesting a possible overlap in their mechanism of action.

Study Duration

14 days

Participants

36 male Sprague Dawley rats

Evidence Level

Not specified

Key Findings

1
HBOT and TAK-242 alleviated behavioral signs of CIPN, specifically mechanical allodynia and thermal hyperalgesia, in rats treated with paclitaxel and LPS.
2
TLR4 overexpression in PAC- and PAC/LPS-treated rats was significantly downregulated after HBOT and TAK-242 treatment in the spinal cord dorsal horn and dorsal root ganglion.
3
Western blots showed a significant reduction in TLR4, TRPV1, MyD88, and NF-κB expression in the spinal cord dorsal horn after HBOT and TAK-242 interventions.

Research Summary

This study investigates the potential of hyperbaric oxygen therapy (HBOT) to alleviate paclitaxel-induced peripheral neuropathy (CIPN) in rats. The research focuses on the TLR4-MyD88-NF-κB signaling pathway and the role of inflammation in CIPN. The study uses a TLR4 agonist (LPS) and antagonist (TAK-242) to modulate the inflammatory response in a rat model of CIPN. Behavioral tests and immunoﬂuorescence staining are used to assess the effects of HBOT and TAK-242 on pain and inflammation. The results suggest that HBOT can ameliorate CIPN symptoms by downregulating the TLR4/MyD88/NF-κB signaling pathway and TRPV1 activation. HBOT has an antinociceptive effect on mechanical and heat hyperalgesia.

Practical Implications

Therapeutic Potential

HBOT may offer a non-pharmacological approach to managing CIPN, especially for patients where current treatments are insufficient.

Targeted Treatment

The study suggests that modulating the TLR4-MyD88-NF-κB pathway could be a key strategy in alleviating CIPN symptoms.

Overlap in mechanism

The research demonstrates a possible overlap in mechanism of action between HBOT and TAK-242, suggesting that modulation of TLR4 is a major mechanism of HBOT in suppressing CIPN.

Study Limitations

1
The effectiveness of HBOT for CIPN in the peripheral neuron system should be further investigated.
2
Future studies with larger sample sizes and diverse animal models are needed to confirm the expression of TLR4 in the spinal cord dorsal horn.
3
A dose–response approach is necessary for future studies to gain more mechanistic information.

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