Abstract
Objective
Functional dyspepsia (FD), which has a complicated pathophysiologic process, is a
common functional gastrointestinal disease. Gastric hypersensitivity is the key pathophysiological
factor in patients with FD with chronic visceral pain. Auricular vagal nerve stimulation
(AVNS) has the therapeutic effect of reducing gastric hypersensitivity by regulating
the activity of the vagus nerve. However, the potential molecular mechanism is still
unclear. Therefore, we investigated the effects of AVNS on the brain-gut axis through
the central nerve growth factor (NGF)/ tropomyosin receptor kinase A (TrkA)/phospholipase
C-gamma (PLC-γ) signaling pathway in FD model rats with gastric hypersensitivity.
Materials and Methods
We established the FD model rats with gastric hypersensitivity by means of colon administration
of trinitrobenzenesulfonic acid on ten-day-old rat pups, whereas the control rats
were given normal saline. AVNS, sham AVNS, K252a (an inhibitor of TrkA, intraperitoneally),
and K252a + AVNS were performed on eight-week-old model rats for five consecutive
days. The therapeutic effect of AVNS on gastric hypersensitivity was determined by
the measurement of abdominal withdrawal reflex response to gastric distention. NGF
in gastric fundus and NGF, TrkA, PLC-γ, and transient receptor potential vanilloid
1 (TRPV1) in the nucleus tractus solitaries (NTS) were detected separately by polymerase
chain reaction, Western blot, and immunofluorescence tests.
Results
It was found that a high level of NGF in gastric fundus and an upregulation of the
NGF/TrkA/PLC-γ signaling pathway in NTS were manifested in model rats. Meanwhile,
both AVNS treatment and the administration of K252a not only decreased NGF messenger
ribonucleic acid (mRNA) and protein expressions in gastric fundus but also reduced
the mRNA expressions of NGF, TrkA, PLC-γ, and TRPV1 and inhibited the protein levels
and hyperactive phosphorylation of TrkA/PLC-γ in NTS. In addition, the expressions
of NGF and TrkA proteins in NTS were decreased significantly after the immunofluorescence
assay. The K252a + AVNS treatment exerted a more sensitive effect on regulating the
molecular expressions of the signal pathway than did the K252a treatment.
Conclusion
AVNS can regulate the brain-gut axis effectively through the central NGF/TrkA/PLC-γ
signaling pathway in the NTS, which suggests a potential molecular mechanism of AVNS
in ameliorating visceral hypersensitivity in FD model rats.
Keywords
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Article info
Publication history
Published online: February 16, 2023
Accepted:
January 18,
2023
Received in revised form:
January 12,
2023
Received:
October 13,
2022
Publication stage
In Press Corrected ProofFootnotes
Source(s) of financial support: This work was supported by the Natural Science Funding of Jiangsu Province, China (Number BK20191065).
Conflict of Interest: The authors reported no conflict of interest.
Identification
Copyright
© 2023 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.
