Glutamatergic neurons in the paraventricular nucleus of the hypothalamus participate in the regulation of visceral pain induced by pancreatic cancer in mice

2024 Hepatobiliary Surgery and Nutrition. All rights reserved..

Background: Visceral pain induced by pancreatic cancer seriously affects patients' quality of life, and there is no effective treatment, because the mechanism of its neural circuit is unknown. Therefore, the aim of this study is to explore the main neural circuit mechanism regulating visceral pain induced by pancreatic cancer in mice.

Methods: The mouse model of pancreatic cancer visceral pain was established on C57BL/6N mice by pancreatic injection of mPAKPC-luc cells. Abdominal mechanical hyperalgesia and hunch score were performed to assess visceral pain; the pseudorabies virus (PRV) was used to identify the brain regions innervating the pancreas; the c-fos co-labeling method was used to ascertain the types of activated neurons; in vitro electrophysiological patch-clamp technique was used to record the electrophysiological activity of specific neurons; the calcium imaging technique was used to determine the calcium activity of specific neurons; specific neuron destruction and chemogenetics methods were used to explore whether specific neurons were involved in visceral pain induced by pancreatic cancer.

Results: The PRV injected into the pancreas was detected in the paraventricular nucleus of the hypothalamus (PVN). Immunofluorescence staining showed that the majority of c-fos were co-labeled with glutamatergic neurons in the PVN. In vitro electrophysiological results showed that the firing frequency of glutamatergic neurons in the PVN was increased. The calcium imaging results showed that the calcium activity of glutamatergic neurons in the PVN was enhanced. Both specific destruction of glutamatergic neurons and chemogenetics inhibition of glutamatergic neurons in the PVN alleviated visceral pain induced by pancreatic cancer.

Conclusions: Glutamatergic neurons in the PVN participate in the regulation of visceral pain induced by pancreatic cancer in mice, providing new insights for the discovery of effective targets for the treatment of pancreatic cancer visceral pain.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:13

Enthalten in:

Hepatobiliary surgery and nutrition - 13(2024), 2 vom: 03. Apr., Seite 258-272

Sprache:

Englisch

Beteiligte Personen:

Ji, Ning-Ning [VerfasserIn]
Cao, Shuang [VerfasserIn]
Song, Xing-Lei [VerfasserIn]
Pei, Bei [VerfasserIn]
Jin, Chen-Yu [VerfasserIn]
Fan, Bi-Fa [VerfasserIn]
Jiang, Hong [VerfasserIn]
Xia, Ming [VerfasserIn]

Links:

Volltext

Themen:

Glutamatergic neurons
Journal Article
Pancreatic cancer
Paraventricular nucleus of the hypothalamus (PVN)
Visceral pain

Anmerkungen:

Date Revised 16.04.2024

published: Print-Electronic

Citation Status PubMed-not-MEDLINE

doi:

10.21037/hbsn-23-442

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM371068010