Activation of Neuroinflammation via mTOR Pathway is Disparately Regulated by Differential Target Multiplexed and Traditional Low-Rate Spinal Cord Stimulation in a Neuropathic Pain Model

Journal of Pain Research, 2022 · DOI: https://doi.org/10.2147/JPR.S378490 · Published: September 13, 2022

Simple Explanation

Spinal cord stimulation (SCS) is a treatment for neuropathic pain, but how it works isn't fully understood. This study looks at the mTOR pathway, which is important in chronic pain, and how two types of SCS affect it. The study used a nerve injury model in animals and treated them with either differential target multiplexed SCS (DTMP) or traditional low-rate SCS (LR-SCS). The researchers then analyzed proteins in the spinal cord to see how the mTOR pathway was affected. The results showed that both DTMP and LR-SCS can reverse changes in the mTOR pathway caused by the nerve injury, with DTMP having a stronger effect. This suggests that SCS works by changing the way cells signal in the spinal cord, reducing inflammation and pain.

Study Duration

48 hours

Participants

Male Sprague-Dawley rats (n = 10 per group)

Evidence Level

Not specified

Key Findings

1
DTMP and LR-SCS reverse injury-induced changes of the mTOR pathway while treating neuropathic pain.
2
DTMP has a stronger effect on regulating the mTOR pathway compared to traditional LR-SCS.
3
Phosphoproteomic analysis showed DTMP back-regulated 65.5% of the isoforms affected by the pain model, while LR-SCS back-regulated 58.0% of them.

Research Summary

This study investigates the effects of differential target multiplexed spinal cord stimulation (DTMP) and traditional low-rate spinal cord stimulation (LR-SCS) on the mTOR pathway in a neuropathic pain model. Proteomic and phosphoproteomic analyses reveal that both DTMP and LR-SCS reverse injury-induced changes in the mTOR pathway, with DTMP exhibiting a more pronounced effect. The findings suggest that SCS's mechanism of action involves modulating molecular pathways, particularly the mTOR pathway, rather than solely disrupting pain signals.

Practical Implications

Therapeutic Potential

DTMP may offer a more effective approach to managing neuropathic pain by targeting the mTOR pathway.

Mechanism of Action

The study provides insights into the molecular mechanisms underlying SCS, highlighting the role of mTOR pathway modulation.

Personalized Treatment

Understanding the differential effects of DTMP and LR-SCS may lead to more personalized treatment strategies for neuropathic pain.

Study Limitations

1
The study used an animal model, which may not fully translate to human conditions.
2
The experimental design for protein quantification may have missed transient proteins or small peptides.
3
The exact cell type responsible for mTOR downstream effects is unclear.

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