Mesenchymal stromal cells alleviate neuropathic pain in association with M2 macrophage polarization in dorsal root ganglia and peripheral nerve repair

BMC Anesthesiol. 2026 Jun 29. doi: 10.1186/s12871-026-04055-9. Online ahead of print.

ABSTRACT

BACKGROUND: Neuropathic pain (NP) is a debilitating condition with limited effective treatments. Mesenchymal stromal cells (MSCs) have emerged as a potential therapeutic strategy due to their immunomodulatory properties. This study investigated whether intravenous administration of human umbilical cord-derived MSCs could alleviate NP in a rat chronic constriction injury (CCI) model and explored the associated changes in macrophage polarization and nerve structure.

METHODS: Male Sprague Dawley rats were subjected to CCI of the sciatic nerve and randomly divided into Control, CCI, and CCI+MSCs groups (n = 10/group). The CCI+MSCs group received 1 × 10⁶ MSCs via tail vein injection on postoperative day 7. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were assessed at baseline and on postoperative days 1, 3, 5, 7, 10, and 15. On day 15, dorsal root ganglia (DRG) were collected for immunofluorescence staining of CD68 (pan-macrophage marker) and CD206 (M2 marker), and sciatic nerves were examined by hematoxylin-eosin staining and transmission electron microscopy (TEM).

RESULTS: CCI induced significant mechanical and thermal hypersensitivity from postoperative day 7 through day 15 (p < 0.05 vs. Control). MSC administration partially restored MWT and TWL values compared with the CCI group (p < 0.05). Immunofluorescence revealed increased CD68⁺ macrophage infiltration in the DRG of CCI rats, which was attenuated by MSC treatment. Concurrently, CD206 expression was enhanced in the CCI+MSCs group, suggesting a shift toward an M2-like macrophage phenotype. Histological and ultrastructural analyses showed that MSC treatment was associated with reduced inflammatory cell infiltration, increased Schwann cell counts, lower G-ratio, and improved myelin sheath integrity compared with the untreated CCI group (p < 0.05).

CONCLUSIONS: Intravenous MSC administration was associated with attenuation of nociceptive hypersensitivity, enhanced M2-like macrophage polarization in the DRG, and partial structural repair of the injured sciatic nerve in a rat CCI model. These findings suggest that MSCs may represent a promising cell-based approach for NP treatment, although further studies are needed to establish causal mechanisms and evaluate long-term safety and efficacy.

PMID:42374223 | DOI:10.1186/s12871-026-04055-9