PDF(Pubmed)
Abstract：
The dorsal raphe nucleus (DRN) is an important nucleus in pain regulation. However, the underlying neural pathway and the function of specific cell types remain unclear. Here, we report a previously unrecognized ascending facilitation pathway, the DRN to the mesoaccumbal dopamine (DA) circuit, for regulating pain. Chronic pain increased the activity of DRN glutamatergic, but not serotonergic, neurons projecting to the ventral tegmental area (VTA) (DRNGlu-VTA) in male mice. The optogenetic activation of DRNGlu-VTA circuit induced a pain-like response in naive male mice, and its inhibition produced an analgesic effect in male mice with neuropathic pain. Furthermore, we discovered that DRN ascending pathway regulated pain through strengthened excitatory transmission onto the VTA DA neurons projecting to the ventral part of nucleus accumbens medial shell (vNAcMed), thereby activated the mesoaccumbal DA neurons. Correspondingly, optogenetic manipulation of this three-node pathway bilaterally regulated pain behaviors. These findings identified a DRN ascending excitatory pathway that is crucial for pain sensory processing, which can potentially be exploited toward targeting pain disorders.
摘要：
背中缝核（DRN）是疼痛调节的重要核。然而,潜在的神经通路和特定细胞类型的功能仍不清楚.这里,我们报告了一个以前未被识别的上升促进途径，DRN到中伏隔多巴胺(DA)回路，调节疼痛。慢性疼痛增加了DRN谷氨酸能的活性，但不是血清素,在雄性小鼠中投射到腹侧被盖区（VTA）（DRNGlu-VTA）的神经元。DRNGlu-VTA回路的光遗传学激活在幼稚的雄性小鼠中诱导了疼痛样反应，其抑制在患有神经性疼痛的雄性小鼠中产生了镇痛作用。此外，我们发现DRN上行通路通过增强兴奋性传递到VTADA神经元上，投射到伏隔核内侧壳的腹侧部分（vNAcMed）来调节疼痛，从而激活了中伏隔DA神经元。相应地,光遗传学操纵这三节点途径双侧调节疼痛行为。这些发现确定了DRN上升兴奋性通路，这对疼痛感觉处理至关重要，这可能被用于治疗疼痛障碍。意义声明中脑的中缝背核（DRN）有助于疼痛处理，然而，详细的细胞和电路机制仍然很大程度上未知。这里,我们报告说，慢性疼痛增加了DRN谷氨酸能神经元的特定亚群的活性，伸向腹侧被盖区（VTA）。DRN谷氨酸能神经元的兴奋性升高会导致对VTA多巴胺神经元的兴奋性输入增加，从而选择性地支配伏隔核内侧壳（vNAcMed）的腹侧部分。DRN-VTA-vNAcMed途径的光遗传学激活诱导VTA中的神经元可塑性并导致疼痛超敏反应。这些发现揭示了上升的DRN兴奋回路如何参与疼痛的感觉调节。
