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

## TL;DR

Combining Bumetanide and MGE cell transplantation reduces neuropathic pain after spinal cord injury in mice by targeting multiple mechanisms.

## Contribution

The study reveals a novel combined therapeutic strategy with additive mechanisms for treating SCI-induced neuropathic pain.

## Key findings

- Bu+Mge significantly relieved SCI-induced neuropathic pain compared to monotherapies.
- The combination inhibited inflammation via the NF-κB pathway and microglia activation.
- It corrected NKCC1/KCC2 imbalance and protected neurons and myelin sheaths.

## Abstract

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.

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.

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.

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.