Mesenchymal stem cells' exosomes alleviate chronic visceral pain through Nrf-2-mediated oxidative stress pathway in rats.

Introduction: Irritable bowel syndrome (IBS) is a prevalent chronic functional gastrointestinal disorder characterized by visceral hypersensitivity (VH), affecting over 10% of the global population. Current treatments for IBS have notable limitations, highlighting the need for novel therapeutic strategies to address chronic visceral pain and associated comorbidities. Methods: High-quality BMSC-Exos were isolated and characterized. In vitro, their neuroprotective effects were assessed in oxidatively stressed neurons. In vivo, IBS model rats received intrathecal injections of BMSC-Exos, and their effects on visceral pain sensitivity and anxiety-like behaviors were evaluated. Spinal cord tissues were analyzed to determine modulation of the Nrf-2/HO-1 pathway. Results: In vitro studies demonstrated that BMSC-Exos effectively rescued oxidative stress-induced neuronal damage. In IBS rats, intrathecally administered BMSC-Exos were internalized by spinal cord neurons, significantly reducing visceral hypersensitivity and anxiety-like behaviors. Mechanistically, BMSC-Exos upregulated the Nrf-2/HO-1 antioxidant pathway, mitigating oxidative stress-induced neuronal damage. Conclusion: These findings demonstrate that BMSC-Exos alleviate chronic visceral pain and comorbid anxiety in IBS rats, likely through Nrf-2/HO-1-mediated oxidative stress reduction in spinal neurons. These results highlight BMSC-Exos as a promising acellular therapeutic strategy for IBS, offering potential applications for this debilitating disorder.