Involvement of dopamine system in the regulation of the brain corticotropin-releasing hormone in paraventricular nucleus in a rat model of chronic visceral pain
Involvement of dopamine system in the regulation of the brain corticotropin-releasing hormone in paraventricular nucleus in a rat model of chronic visceral pain
复制标题
多巴胺系统参与慢性内脏痛大鼠模型室旁核脑促肾上腺皮质激素释放激素的调节
DOI：
10.1080/01616412.2018.1460702
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发表时间：
2018-01-01
影响因子：
1.9
通讯作者：
Zhang, Yong-Mei
中科院分区：
文献类型：
--
作者：
Ji, Ning-Ning;Kang, Jie;Zhang, Yong-Mei
目的：本研究采用新生大鼠和成年大鼠结直肠扩张（CRD）模型，探讨室旁核（PVN）和腹侧被盖区（VTA）环路在内脏痛-抑郁发病机制中的作用。新生雄性Sprague-Dayley（SD）大鼠在出生后第8、10和12天经历CRD，并且当成熟时，测试成人腹部退缩反射（AWR）评分，以评估内脏高敏感性。采用强迫游泳实验评价抑郁样行为。采用腹侧被盖区注射利多卡因的方法，观察腹侧被盖区与内脏痛的关系。采用免疫荧光双标法检测多巴胺/c-Fos在CRD大鼠脑内的表达。在证实PVN至VTA存在纤维投射后，PVN内注射CRH-RNAi慢病毒抑制CRH表达，通过AWR评分和FST评价行为学变化。结果：腹侧被盖区（VTA）内微量注射利多卡因可提高CRD组大鼠痛阈，而注射利多卡因组大鼠痛阈明显降低。在VTA内显微注射绿色逆行示踪剂后，免疫荧光显微照片显示PVN具有典型的绿色逆行示踪剂。结论：腹侧被盖区在慢性内脏痛和抑郁中起着重要作用，下丘脑室旁核CRH神经元可能通过激活腹侧被盖区多巴胺参与慢性内脏痛和抑郁的发生和维持。
Objective: We aimed to investigate the mechanism of paraventricular nucleus (PVN) and ventral tegmental area (VTA) circuit in the pathogenesis of visceral pain-depression with a rat model induced by neonatal and adult colorectal distension (CRD).Methods: Neonate male Sprague-Dayley (SD) rats underwent CRD on postnatal days 8, 10, and 12, and when matured, were tested for adult abdominal withdrawal reflex (AWR) scores to assess visceral hypersensitivity. The forced swimming test was employed to evaluate depression-like behaviors. The rats exhibiting visceral pain-depressive behaviors underwent lidocaine injection in the VTA to explore the relationship between VTA and visceral pain. Moreover, double immunofluorescence was employed to evaluate the qualitative and quantitative expression of dopamine/c-Fos in CRD rats. After verifying the existed fiber projection from PVN to VTA, the intra-PVN microinjection of CRH-RNAi lentivirus to inhibit corticotropin-releasing hormone (CRH) expression, behavioral changes were assessed by AWR score and FST. Thereafter, with the sacrifice of the rats, the variations of TH protein in rats were evaluated by immunofluorescence and Western blot.Results: Intra-VTA microinjection of lidocaine increased the pain threshold of CRD group. After intra-VTA microinjection of green retrograde tracer, immunofluorescence photomicrographs visualized the PVN with a typical green retrograde tracer. Intra-PVN microinjection of CRH-RNAi lentivirus alleviated the visceral pain-depression behaviors and decreased the TH protein expression in the VTA.Conclusion: These data demonstrated that the VTA played a functional role in chronic visceral pain and depression, and the CRH-containing neurons in hypothalamic PVN may be implicated in the onset and maintenance of the chronic visceral pain and depression via the activation of dopamine in the VTA.