Mechanism of human umbilical cord mesenchymal stem cell-derived exosomes in alleviating neuropathic pain in CCI rats

Neuropathic pain (NP) is a refractory chronic pain disorder with a complex pathogenesis and limited effective treatment options. In recent years, exosomes derived from mesenchymal stem cells (MSC-Exos) have attracted attention as promising therapeutic agents due to their anti-inflammatory, neuroregenerative, and immunomodulatory properties. This study aimed to investigate the therapeutic effects and underlying mechanisms of human umbilical cord mesenchymal stem cell-derived exosomes (hUC-MSC-Exos) in a rat model of neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve. hUC-MSC-Exos were isolated via ultracentrifugation and administered to CCI rats. Behavioral tests demonstrated that hUC-MSC-Exos significantly ameliorated both mechanical allodynia and thermal hyperalgesia in CCI rats. Further mechanistic investigations indicated that hUC-MSC-Exos downregulated the expression of pro-inflammatory cytokines (NF-κB, TNF-α, IL-6) and modulated astrocyte activation and polarization, thereby contributing to neuropathic pain relief. These findings elucidate the potential mechanisms through which hUC-MSC-Exos alleviate NP and provide an experimental foundation for their future clinical application.