# Systematic Review: Preclinical and Clinical Evidence on MSC Efficacy and Mechanism of Action in Neuropathic Pain Reduction

## TL;DR

This review summarizes preclinical studies showing that mesenchymal stem cells (MSCs) reduce neuropathic pain, likely through immune modulation and other mechanisms.

## Contribution

The paper systematically reviews 25 preclinical studies to clarify the mechanisms of MSC efficacy in neuropathic pain.

## Key findings

- 23 out of 25 studies showed reduced neuropathic pain after MSC therapy.
- Pain relief was linked to decreased inflammation, suggesting immune modulation as a key mechanism.
- Inflammation reduction did not always lead to full pain relief, indicating other mechanisms are involved.

## Abstract

Nerve injury often results in neuropathic pain, marked by spontaneous pain, hyperalgesia, and allodynia. Current treatments have moderate efficacy and have side effects, prompting interest in alternative approaches. Mesenchymal stem cell (MSC) therapy has shown promise in preclinical studies for reducing neuropathic pain and inflammation. However, the precise mechanisms underlying MSC-mediated pain reduction remain unclear. Investigating these mechanisms is crucial for optimizing MSC-based therapies for neuropathic pain. This article provides a brief overview of the MSC administration, animal models of neuropathic pain, and treatment regimens used in 25 preclinical studies, focusing on the potential mechanisms of action underlying the neuropathic pain-reducing effect of MSCs. Importantly, 23 out of the 25 studies demonstrated a reduction in neuropathic pain following MSC therapy, despite differences in MSC sources and treatment regimens. Neuropathic pain relief was associated with decreased inflammation, suggesting that MSCs may act through immune modulation. However, the resolution of inflammation does not always correlate with complete neuropathic pain relief, indicating the involvement of additional mechanisms.