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

作　　者：Ning-Ning Ji Shuang Cao Xing-Lei Song Bei Pei Chen-Yu Jin Bi-Fa Fan Hong Jiang Ming Xia 

机构地区：[1]Department of Anesthesiology,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China [2]Department of Anatomy and Physiology,Shanghai Jiao Tong University School of Medicine,Shanghai,China [3]Department of Pain,China-Japan Friendship Hospital,Beijing,China

出　　处：《Hepatobiliary Surgery and Nutrition》2024年第2期258-272,共15页肝胆外科与营养（英文）

基　　金：supported by Shanghai Municipal Science and Technology Major Project(Grant No.23Y11908100 to M.X.);Cross-disciplinary Research Fund of Shanghai Ninth People’s Hospital,Shanghai JiaoTong University School of Medicine(Grant No.JYJC202312 to M.X.);Postdoctoral Research Start-up Fund of Shanghai Ninth People’s Hospital,Shanghai JiaoTong University School of Medicine(to N.N.J.).

摘　　要：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.

关 键 词：Visceral pain pancreatic cancer glutamatergic neurons paraventricular nucleus of the hypothalamus(PVN) 

分 类 号：R441.1[医药卫生—诊断学]