Evidence map›Paper›PMID 41968418›Full record

ArticleNeurogastroenterology and motility2026

Frequency-Dependent Effects of Transauricular Vagus Nerve Stimulation on Alleviating Visceral Hypersensitivity: Involvement of the Nesfatin-1/CRF/CRF1R Pathway.

Wanli Xu, Ziqin Zhou, Shuai Zhou, Ruirui Zhao, Weijian Zhu, Huan Chen, Jingzhu Zhou, Zhaohui Zhang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurogastroenterology and motility, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Wanli XuDepartment of Acupuncture and Moxibustion, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.ORCID https://orcid.org/0000-0003-4322-1906
Ziqin ZhouDepartment of Acupuncture and Moxibustion, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Shuai ZhouDepartment of Acupuncture and Moxibustion, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Ruirui ZhaoCollege of Integrated Traditional and Western Medicine, Jiangsu Health Vocational College, Nanjing, China.
Weijian ZhuDepartment of Acupuncture and Moxibustion, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Huan ChenDepartment of Acupuncture and Moxibustion, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Jingzhu ZhouDepartment of Acupuncture and Moxibustion, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Zhaohui ZhangDepartment of Acupuncture and Moxibustion, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.

Funding

Jiangsu Provincial Health Commission Project（Key Project） ZD2021032Jiangsu TCM Science and Technology Project YB2017089Natural Science Funding of Jiangsu Province BK20191065
6 · The paper itself

Abstract

backgroundVisceral hypersensitivity (VH) is acknowledged as a critical pathogenic mechanism underlying functional gastrointestinal disorders (FGIDs), which is influenced by dysregulation of the gut-brain axis. Transauricular vagus nerve stimulation (taVNS) is a clinically used intervention for the relief of visceral pain; however, its underlying neural mechanisms remain poorly understood. Drawing on the pathogenesis of VH and our team's previous research, we hypothesized that taVNS mitigates VH through the nesfatin-1/corticotropin-releasing factor (CRF) pathway. This study aims to elucidate the potential central regulatory mechanisms that contribute to the analgesic effects of taVNS.

methodsA validated VH model was established in Sprague-Dawley (SD) rats through maternal separation (MS) combined with acetic acid enema. The VH rats underwent taVNS at frequencies of 2 Hz, 10 Hz, and 15 Hz, whereas the sham group received 2 Hz electrical stimulation at the earlobe. The visceral pain threshold was evaluated using the abdominal withdrawal reflex (AWR) scoring and electromyographic activity of the external oblique muscle. Additionally, Western blot analysis was conducted to assess the expression levels of nesfatin-1, CRF, and its receptors 1 and 2 (CRF1/2R) in the hypothalamus. KEY

resultsThe analyses of AWR and electromyogram (EMG) responses indicated that (a) the area under the curve (AUC) of the EMG response to colorectal distension (CRD) at four distension pressures (20, 40, 60, and 80 mmHg) was significantly elevated in the VH group. (b) The AUC was significantly reduced in the 2 Hz taVNS group across all four distension pressures. (c) The 10 Hz taVNS group exhibited a significant decrease in the AUC at 20 mmHg and 40 mmHg. Furthermore, the results of Western blot analysis demonstrated that (a) 2 Hz taVNS significantly lowered the expressions of nesfatin-1, CRF, and CRF1R, aligning with the findings in the sham group. (b) Both 10 Hz and 15 Hz taVNS significantly decreased CRF expression, whereas nesfatin-1 and CRF1R expression remained unchanged. (c) There was no significant downregulation of CRF2R expression among the intervention groups.

conclusionThis study demonstrated that taVNS alleviates VH, potentially via the nesfatin-1/CRF/CRF1R signaling pathway in the rat hypothalamus. Furthermore, the analgesic effect was frequency-dependent, with 2 Hz taVNS providing a more effective reduction in visceral pain.

Indexed as

Calcium-Binding ProteinsDNA-Binding ProteinsNerve Tissue ProteinsReceptors, Corticotropin-Releasing HormoneVagus Nerve StimulationVisceral PainAnimalsMaleNucleobindinsRatsRats, Sprague-DawleySignal TransductionCalcium-Binding ProteinsDNA-Binding ProteinsNerve Tissue ProteinsNucb1 protein, ratNucb2 protein, ratNucleobindinsReceptors, Corticotropin-Releasing HormoneCRFnesfatin‐1Transauricular vagus nerve stimulationvisceral hypersensitivity

Identifiers

PMID41968418
PMCPMC13071134

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.