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

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.

NK_1受体阻滞剂对电针内关穴抗大鼠AMI损伤效应的影响

目的:探讨NK1受体阻滞剂对电针大鼠内关穴抗AMI损伤效应的自主神经及中枢SP、NOS的影响。方法:静注NK1受体阻滞剂观察心交感神经、迷走神经放电频率变化;观察治疗前后下丘脑室旁核、延髓迷走神经复合区及脊髓外侧角SP、NOS灰度值的变化。结果:阻滞剂组与阻滞剂加电针组对AMI大鼠迷走神经和交感神经放电频率无显著性差异;阻滞剂组、阻滞剂加电针组与电针内关组对AMI大鼠迷走神经和交感神经放电频率有显著性差异(△P<0.05);阻滞剂组与阻滞剂加电针组SP在PVN、延髓迷走神经复合区及脊髓外侧角的阳性表达降低,NOS表达降低。结论:静注NK1受体阻滞剂阻断了电针内关对AMI大鼠迷走神经和交感神经放电的良性调节,阻断了SP在PVN、延髓迷走神经复合区及脊髓外侧角的阳性表达,引起NOS表达降低,SP在电针内关穴对AMI保护效应中起到关键作用。