# Electroacupuncture of Guanyuan (CV4) Acupoint Improved Pelvic Inflammatory Disease Pain by Inhibiting Neuroinflammation and Sympathetic Activity

**Authors:** Jinyu Qu, Yingchun Peng, Xuefang Shen, Jin Xiong, Huan Wang, Xiang Xiao, Yili Wang

PMC · DOI: 10.1002/iid3.70299 · Immunity, Inflammation and Disease · 2025-11-05

## TL;DR

Electroacupuncture at the Guanyuan acupoint reduces pelvic inflammatory disease pain in rats by lowering inflammation and sympathetic activity.

## Contribution

This study reveals that electroacupuncture at CV4 alleviates PID pain by inhibiting neuroinflammation and sympathetic activation in a rat model.

## Key findings

- EA at CV4 reduced pain scores and improved mechanical and thermal withdrawal thresholds in PID rats.
- EA at CV4 inhibited sympathetic activity and decreased levels of inflammatory markers like TNF-α and TGF-β1.
- EA at CV4 restored synaptic connections in pelvic nerves and reduced uterine tissue damage.

## Abstract

To investigate the underlying mechanisms through which electroacupuncture (EA) at the Guanyuan (CV4) acupoint inhibits sympathetic activity and neurogenic inflammatory responses to relieve pain in rats with pelvic inflammatory disease (PID).

Escherichia coli and Staphylococcus aureus were used to establish a PID rat model. EA was evaluated at frequencies of 2, 100, and 2/100 Hz, and 2/100 Hz was selected for subsequent investigation. The rats were randomly divided into the control, model, EA‐guanyuan (2/100 Hz), and EA‐nonsensitized groups (n = 6). Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were assessed using von Frey filaments. Hematoxylin and eosin staining was performed to evaluate the histopathology. The tyrosine hydroxylase (TH) expression was analyzed using immunofluorescence (IF) staining. The levels of tumor necrosis factor‐α (TNF‐α), interleukin‐2 (IL‐2), transforming growth factor‐β1 (TGF‐β1), intercellular cell adhesion molecule‐1 (ICAM‐1), 5‐hydroxytryptamine receptor 3 (5‐HT3R), substance P (SP), hyaluronic acid (HA), and bradykinin (BK) were measured using an enzyme‐linked immunosorbent assay (ELISA). Western blot analysis was performed to measure the expression of 5‐HT3R, calcitonin gene‐related peptide (CGRP), HA, Kininogen 1 (KNG1), prostaglandin I2 (PGI2), and trefoil factor 2 (TFF2). Transmission electron microscopy (TEM) was used to observe synaptic connections.

EA at CV4 reduced the behavioral pain score (p < 0.05), increased MWT and TWL, and alleviated uterine tissue pathological damage in rats. EA at CV4 reduced the levels of 5‐HT3R, CGRP, BK, HA, KNG1, PGI2SP, TGF‐β1, ICAM‐1, and TNF‐α, and increased IL‐2 levels (p < 0.05). Furthermore, EA at CV4 inhibited sympathetic activity by decreasing TH expression (p < 0.05). Additionally, EA at CV4 restored the synaptic connections between the pelvic nerves of the dorsal commissural neuron (DCN).

EA at CV4 alleviated the pathological damage and pain sensitization of uterine tissue in rats with PID by inhibiting sympathetic activity and neurogenic inflammatory response.

Electroacupuncture at Guanyuan (CV4) acupoint reduced the behavioral pain score and alleviated the pathological damage and pain sensitization of uterine tissue in PID rats by inhibiting sympathetic activity and neurogenic inflammatory response.

## Linked entities

- **Genes:** TNF (tumor necrosis factor) [NCBI Gene 7124], IL2 (interleukin 2) [NCBI Gene 3558], TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040], ICAM1 (intercellular adhesion molecule 1) [NCBI Gene 3383], HTR3A (5-hydroxytryptamine receptor 3A) [NCBI Gene 3359], CALCA (calcitonin related polypeptide alpha) [NCBI Gene 796], ha (hair bristles) [NCBI Gene 251217], KNG1 (kininogen 1) [NCBI Gene 3827], KNG1 (kininogen 1) [NCBI Gene 3827], PGI2 (hypothetical protein) [NCBI Gene 20227689], TFF2 (trefoil factor 2) [NCBI Gene 7032], TH (tyrosine hydroxylase) [NCBI Gene 7054]
- **Proteins:** TNF (tumor necrosis factor), IL2 (interleukin 2), TGFB1 (transforming growth factor beta 1), ICAM1 (intercellular adhesion molecule 1), HTR3A (5-hydroxytryptamine receptor 3A), CALCA (calcitonin related polypeptide alpha), ha (hair bristles), KNG1 (kininogen 1), KNG1 (kininogen 1), PGI2 (hypothetical protein), TFF2 (trefoil factor 2), TH (tyrosine hydroxylase)
- **Diseases:** pelvic inflammatory disease (MONDO:0000922), PID (MONDO:0000922)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Htr3a (5-hydroxytryptamine receptor 3A) [NCBI Gene 79246] {aka 5-HT3, 5-HT3A, 5HT3, Htr3}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 59086] {aka Tgfb}, Syt17 (synaptotagmin 17) [NCBI Gene 192189] {aka Bk}, Calca (calcitonin-related polypeptide alpha) [NCBI Gene 24241] {aka CAL6, CGRP, CGRP1, Cal1, Calc, RATCAL6}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Th (tyrosine hydroxylase) [NCBI Gene 25085] {aka The}, Icam1 (intercellular adhesion molecule 1) [NCBI Gene 25464] {aka CD54, ICAM, RICAM-I}, Tff2 (trefoil factor 2) [NCBI Gene 116592], Il2 (interleukin 2) [NCBI Gene 116562], Kng2 (kininogen 2) [NCBI Gene 24903] {aka KINKG, KINKH, KINT1G, Kng, Kng1, Kng1_v1}
- **Diseases:** tissue pathological damage (MESH:D017695), PID (MESH:D000292), inflammatory (MESH:D007249), Pain (MESH:D010146), Neuroinflammation (MESH:D000090862), pathological damage (MESH:D005598)
- **Chemicals:** HA (MESH:D006820), CV4 (-), eosin (MESH:D004801), PGI2 (MESH:D011464), Hematoxylin (MESH:D006416)
- **Species:** Staphylococcus aureus (species) [taxon 1280], Rattus norvegicus (brown rat, species) [taxon 10116], Escherichia coli (E. coli, species) [taxon 562]

## Full text

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## Figures

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## References

49 references — full list in the complete paper: https://tomesphere.com/paper/PMC12589820/full.md

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Source: https://tomesphere.com/paper/PMC12589820