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Inhibition of GABAergic neurons in the paraventricular nucleus of the hypothalamus precipitates visceral pain induced by pancreatic cancer in mice.
Ji, Ning-Ning; Li, Zhi-Yan; Cao, Shuang; Pei, Bei; Jin, Chen-Yu; Li, Yi-Fan; Mao, Peng; Jiang, Hong; Fan, Bi-Fa; Xia, Ming.
Afiliación
  • Ji NN; Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Li ZY; The Chinese Translational Research Center for Pain Medicine, Beijing, China.
  • Cao S; Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Pei B; Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Jin CY; Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Li YF; Department of Pain, China-Japan Friendship Hospital, Beijing, China.
  • Mao P; Department of Pain, China-Japan Friendship Hospital, Beijing, China.
  • Jiang H; Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Fan BF; Department of Pain, China-Japan Friendship Hospital, Beijing, China.
  • Xia M; Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
J Gastrointest Oncol ; 15(1): 458-467, 2024 Feb 29.
Article en En | MEDLINE | ID: mdl-38482250
ABSTRACT

Background:

For patients with pancreatic cancer, visceral pain is a debilitating symptom that significantly compromises their quality of life. Unfortunately, the lack of effective treatment options can be attributed to our limited understanding of the neural circuitry underlying this phenomenon. The primary objective of this study is to elucidate the fundamental mechanisms governing visceral pain induced by pancreatic cancer in murine models.

Methods:

A mouse model of pancreatic cancer visceral pain was established in C57BL/6N mice through the intrapancreatic injection of mPAKPC-luc cells. Abdominal mechanical hyperalgesia and hunch score were employed to evaluate visceral pain, whereas the in vitro electrophysiological patch-clamp technique was utilized to record the electrophysiological activity of GABAergic neurons. Specific neuron ablation and chemogenetics methods were employed to investigate the involvement of GABAergic neurons in pancreatic cancer-induced visceral pain.

Results:

In vitro electrophysiological results showed that the firing frequency of GABAergic neurons in the paraventricular nucleus of the hypothalamus (PVN) was decreased. Specific destruction of GABAergic neurons in the PVN exacerbated visceral pain induced by pancreatic cancer. Chemogenetics activation of GABAergic neurons in the PVN alleviated visceral pain induced by pancreatic cancer.

Conclusions:

GABAergic neurons located in PVN play a crucial role in precipitating visceral pain induced by pancreatic cancer in mice, thereby offering novel insights for identifying effective targets to treat pancreatic cancer-related visceral pain.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Gastrointest Oncol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: China
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Gastrointest Oncol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: China