# Stauntonia chinensis injection relieves neuropathic pain by increasing the expression of PSD‐95 and reducing the proliferation of phagocytic microglia

## TL;DR

A traditional Chinese medicine injection relieves neuropathic pain in mice by boosting a brain protein and reducing harmful immune cell activity in the spinal cord.

## Contribution

The study reveals a novel mechanism by which Stauntonia chinensis injection alleviates neuropathic pain through PSD-95 upregulation and microglia inhibition.

## Key findings

- SCI injection reduces mechanical and thermal hyperalgesia in CCI mice.
- SCI decreases microglia proliferation and increases PSD-95 expression in the spinal cord.
- SCI inhibits neuroinflammation and neuron overactivity in neuropathic pain models.

## Abstract

Neuroinflammation induced by engulfment of synapses by phagocytic microglia plays a crucial role in neuropathic pain. Stauntonia chinensis is extracted from Stauntonia chinensis DC, which has been used as a traditional Chinese medicine to control trigeminal neuralgia or sciatica. However, the specific anti‐neuralgia mechanism of Stauntonia chinensis is unknown. In this study, the analgesic effect of Stauntonia chinensis injection (SCI) in mice with neuropathic pain and the possible mechanisms are explored. We find that a local injection of 0.1 mL Stauntonia chinensis for 14 days can considerably relieve mechanical hyperalgesia and thermal hyperalgesia in mice with sciatic chronic constriction injury (CCI). Immunofluorescence staining shows that SCI reduces neuroinflammation in the spinal cord of CCI mice. RNA sequencing reveals that the expression of postsynaptic density protein 95 (PSD‐95), a postsynaptic scaffold protein, is downregulated in the spinal cord of CCI mice, but upregulated after SCI administration. Immunofluorescence experiments also demonstrate that SCI administration reverses microglia proliferation and PSD‐95 downregulation in CCI mice. These data suggest that SCI relieves neuropathic pain by increasing the expression of PSD‐95 and reducing the proliferation of phagocytic microglia.

Schematic diagram of the mechanism of Stauntonia chinensis injection (SCI) inhibiting neuropathic pain. Sciatic chronic constriction injury can cause inflammatory activation of spinal microglia, proliferation of phagocytic microglia, and prominent phagocytosis, resulting in a decrease in postsynaptic density protein 95 (PSD‐95). Simultaneously activated microglia release pro‐inflammatory cytokines, leading to an increase in neuroinflammation and an increase in neuronal action potentials (spikes), exacerbating neuropathic pain. SCI can inhibit the proliferation of phagocytic microglia and therefore increase PSD‐95 and inhibit the expression of inflammatory cytokines, as well as neuroinflammation and neuron spikes in the spinal cord.