UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
■通过胰腺注射mPAKPC-luc细胞在C57BL/6N小鼠上建立胰腺癌内脏痛小鼠模型。进行腹部机械性痛觉过敏和预感评分以评估内脏疼痛;使用伪狂犬病病毒(PRV)来识别支配胰腺的大脑区域;使用c-fos共标记方法来确定激活的神经元的类型;使用体外电生理膜片钳技术来记录特定神经元的电生理活动;使用钙成像技术来确定特定神经元的钙活性。通过化学方法来探索特定神经元是否参与了特定的胰腺疼痛。
■在下丘脑室旁核(PVN)中检测到注射到胰腺中的PRV。免疫荧光染色显示大多数c-fos与PVN中的谷氨酸能神经元共标记。体外电生理结果表明,PVN中谷氨酸能神经元的放电频率增加。钙成像结果表明,PVN中谷氨酸能神经元的钙活性增强。PVN中谷氨酸能神经元的特异性破坏和谷氨酸能神经元的化学遗传学抑制均减轻了胰腺癌引起的内脏疼痛。
■PVN中的谷氨酸能神经元参与小鼠胰腺癌内脏痛的调节,为发现治疗胰腺癌内脏痛的有效靶点提供新的见解。