# Tuina Alleviates Anxiety‐Like Behaviors Associated With Neuropathic Pain Through the Modulation of Synaptic Plasticity in the Anterior Cingulate Cortex

## TL;DR

Tuina, a traditional Chinese therapy, reduces pain and anxiety in rats by improving brain connections in the anterior cingulate cortex.

## Contribution

This study shows Tuina alleviates neuropathic pain and anxiety by modulating synaptic plasticity and specific protein expressions in the ACC.

## Key findings

- Tuina increased pain thresholds and reduced anxiety-like behaviors in CCI rats.
- Tuina reversed abnormal synaptic structure remodeling and excitatory synaptic transmission in the ACC.
- Tuina modulated the expression of PSD-95, GluN2B, GluR1, and CaMKII in the ACC.

## Abstract

As the disease progresses, neuropathic pain (NP) is often accompanied by anxiety‐like behaviors, which are associated with plastic changes in the synaptic structure and function within the anterior cingulate cortex (ACC). Tuina is a traditional Chinese manual therapy. This study aims to investigate the effects of Tuina on pain behaviors and related anxiety‐like behaviors in rats with the chronic constriction injury (CCI) model, as well as its impact on synaptic plasticity in the ACC.

The rats were randomly divided into three groups: Sham, CCI, and Tuina. An NP comorbid anxiety model was established by inducing CCI in the right sciatic nerve. The pain‐related behaviors and anxiety‐like behaviors in rats were assessed using the mechanical withdrawal threshold (MWT), thermal withdrawal latency (TWL), open field test (OFT), and elevated plus maze (EPM). Supplementary Material The changes in the synaptic ultrastructure within the ACC were examined using transmission electron microscopy (TEM). The changes in excitatory synaptic transmission (synaptic function) within the ACC were investigated using the whole‐cell patch‐clamp technique. The expression levels of the postsynaptic proteins PSD‐95, GluN2B, GluR1, and CaMKII in the ACC were analyzed using Western blot.

Tuina significantly elevated the pain threshold in CCI rats and mitigated their anxiety‐like behaviors. Tuina alleviated the abnormal remodeling of synaptic structures in the ACC and mitigated the CCI‐mediated enhancement of excitatory synaptic transmission. Tuina may exert its analgesic and anxiolytic effects by modulating the expression of postsynaptic proteins PSD‐95, glutamate receptor GluN2B, GluR1, and the downstream protein CaMKII in the ACC.

Tuina effectively alleviates pain sensitivity and anxiety‐like behaviors in CCI model rats while modulating abnormal synaptic remodeling in the ACC. This study provides fundamental experimental evidence supporting Tuina as a potential therapeutic option for NP associated with anxiety‐like behaviors.

Tuina alleviates CCI‐induced neuropathic pain and anxiety‐like behaviors, and counteracts the enhancement of excitatory synaptic transmission and abnormal synaptic plasticity, potentially by modulating GluN2B/PSD‐95/CaMKII/GluR1 signaling.