Intrathecal Injection of SIRT1-modified Human Mesenchymal Stem Cells Alleviates Neuropathic Pain in Rat

Accumulating evidence has elucidated that human mesenchymal stem cells (hMSCs) exert profound analgesic effects on numerous animal models of neuropathic pain, including drug-induced peripheral nerves, diabetes-induced neuropathy, and chronic constriction injury. We aimed to address whether forcing expression of sirtuin 1 (SIRT1) can enhance the efficacy of hMSCs on alleviation of pain sensation. A rat model of chronic constriction injury (CCI) mimicking peripheral nerve injury was incorporated in the study. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) testing were used to measure pain-related behavior. Our results demonstrated that SIRT1 was decreased post-CCI surgery. Compared to hMSCs-control implantation, the hMSCs-SIRT1 (hMSCs overexpressing SIRT1) implantation exhibited superior effects on reducing pro-inflammatory cytokine levels in serum and spinal dorsal horn, while ameliorating neuropathic pain in CCI rat. Engineering hMSCs such as overexpressing SIRT1 may serve as a promising strategy for the treatment of patients with neuropathic pain.