# Rotating-pulling-poking manipulation effectively alleviates pain symptoms of lateral ankle sprain: an animal experimental study

**Authors:** Haibao Wen, Jinghua Gao, Fudong Shi, Jin Li, Minrui Fu, Minshan Feng, Luguang Li, Chunyu Gao, Jianguo Li

PMC · DOI: 10.3389/fpain.2025.1532867 · 2025-06-23

## TL;DR

This study shows that a specific manipulation technique can reduce pain from ankle sprains in rats by affecting brain pathways and inflammation.

## Contribution

The study identifies the analgesic mechanism of Rotating-Pulling-Poking Manipulation through brain signaling and inflammation reduction in an animal model.

## Key findings

- The 5-minute manipulation group showed the best analgesic effect with reduced pain thresholds and weight-bearing differences.
- Manipulation increased MOR and 5-HT levels while decreasing BDNF, p-TrkB/TrkB, NR2A, and inflammatory markers in ankle tissues.
- The technique activates descending pain inhibition and suppresses pain facilitation and inflammation pathways.

## Abstract

This study aimed to explore the analgesic mechanism of the Rotating - Pulling - Poking Manipulation in treating acute lateral ankle sprain (ALAS). Thirty rats were randomly divided into 5 groups in the first experiment to determine the dose - effect relationship by detecting ankle pain thresholds at different time points. The results showed that the 5-min manipulation group had the best analgesic effect, with the bipedal weight - bearing difference decreasing over time and pain relief time shortened. In the second experiment, 30 rats were divided into 3 groups. After manipulation, samples from PAG and RVM were tested. The results indicated that compared with the model group, the 5-min manipulation group had increased MOR expression in PAG and 5 - HT concentration in cerebrospinal fluid, decreased expressions of BDNF, p - TrkB/TrkB in PAG and NR2A in RVM, and reduced contents of IL - 6, IL - 1β, TNF - α in ankle soft tissues. In conclusion, the Rotating - Pulling - Poking Manipulation can relieve pain by exciting the descending inhibitory system mediated by opioid receptors in the brain center, weakening the descending facilitation system mediated by the BDNF/TrkB/NR2A signaling pathway, and reducing the inflammatory response.

## Linked entities

- **Proteins:** OPRM1 (opioid receptor mu 1), BDNF (brain derived neurotrophic factor), NTRK2 (neurotrophic receptor tyrosine kinase 2), GRIN2A (glutamate ionotropic receptor NMDA type subunit 2A), 5-HT1B (5-hydroxytryptamine (serotonin) receptor 1B)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Bdnf (brain-derived neurotrophic factor) [NCBI Gene 24225], Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, Grin2a (glutamate ionotropic receptor NMDA type subunit 2A) [NCBI Gene 24409] {aka GluN2A, NMDAR2A, NR2A}, Ntrk2 (neurotrophic receptor tyrosine kinase 2) [NCBI Gene 25054] {aka RATTRKB1, TRKB1, Tkrb, trk-B, trkB}
- **Diseases:** ankle pain (MESH:D010146), inflammatory (MESH:D007249), ALAS (MESH:D016512)
- **Chemicals:** 5 - HT (MESH:D012701)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12230092/full.md

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Source: https://tomesphere.com/paper/PMC12230092