Combined use of Bumetanide and MGE cell transplantation alleviates neuropathic pain and its mechanism after spinal cord injury in mice

Published on April 3, 2026

Front Immunol. 2026 Mar 18;17:1751436. doi: 10.3389/fimmu.2026.1751436. eCollection 2026.

ABSTRACT

INTRODUCTION: Neuropathic pain (NP) after spinal cord injury (SCI) is intractable with limited efficacy of single treatments. This study investigated the additive analgesic effect and molecular mechanisms of Bumetanide (Bu, a NKCC1 inhibitor) combined with medial ganglionic eminence (MGE) cell transplantation on SCI-induced NP.

METHODS: Ninety adult female C57BL/6N mice were randomly divided into 5 groups (Sham, SCI, Bu, Mge, Bu+Mge). A T10 moderate spinal cord contusion model was established, with treatments (Bu intraperitoneal injection and MGE orthotopic transplantation) on day 10 post-surgery. Behavioral assessments, ELISA, Western blotting, qRT-PCR, and immunofluorescence staining were used.

RESULTS: Compared with monotherapy, Bu+Mge significantly relieved SCI-induced NP. Mechanistically, it alleviated inflammation by inhibiting NF-κB pathway and microglia activation, rectified spinal cord and dorsal root ganglion NKCC1/KCC2 imbalance, increased GABA-A receptors and GAD65/67 mRNA, reduced glial scarring, and protected neurons, axons and myelin sheaths.

DISCUSSION: Bu combined with MGE cell transplantation relieves SCI-induced NP via multiple additive mechanisms, providing a novel theoretical basis and potential clinical strategy for NP treatment.

PMID:41929507 | PMC:PMC13038438 | DOI:10.3389/fimmu.2026.1751436

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