EXPRESS: Study on the Role and Mechanism of the IL-10-IRF-8 Signaling Pathway in Bone Marrow Mesenchymal Stem Cell Therapy for Pain in CCD Rats

Mol Pain. 2026 Feb 27:17448069261432034. doi: 10.1177/17448069261432034. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the analgesic effects and mechanisms of IL-10-modified BMSCs administered via intrathecal injection in CCD rats.

PATIENTS AND METHODS: After CCD surgery, rats were administered intrathecal injections of PBS, BMSCs, BMSCs-IL-10+, BMSCs-IL-10++Anti-IL-10, LV-IRF-8, and LV-IRF-8+IL-10. Pain was assessed by measuring the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL). Glial cell activation and M2 microglial polarization were evaluated by immunofluorescence staining of Iba-1, GFAP, and Arg-1, and by WB for Iba-1 and Arg-1. Spinal cord inflammation was assessed by PCR analysis of TGF-β, TNF-α, and IL-1β expression.

RESULTS: Compared with the CCD+PBS group, intrathecal injection of both BMSCs and BMSCs-IL-10+ significantly alleviated CCD-induced mechanical and thermal pain. However, the analgesic effect of the BMSCs group markedly decreased after 4 days, while the BMSCs-IL-10+ group lasted at least 14 days. The BMSCs-IL-10+ group significantly upregulated the expression of TGF-β while downregulating TNF-α and IL-1β, inhibiting glial cell activation and promoting M2 microglia polarization. These effects were superior to the BMSCs group and could be abolished by anti-IL-10 antibody. IRF-8 overexpression exacerbated pain and inflammation in CCD rats, but the combined application of IL-10 protein reversed this impact.

CONCLUSION: IL-10 is a key cytokine mediating the analgesic effects of BMSCs. Transplantation of BMSCs-IL-10+ cells reduces glial activation, alleviates neuroinflammation, and relieves neuropathic pain by enhancing IL-10 expression and suppressing IRF-8.

PMID:41757709 | DOI:10.1177/17448069261432034