PDF(Pubmed)
Abstract：
While visceral pain is commonly associated with disorders of the gut-brain axis, underlying mechanisms are not fully understood. Dorsal root ganglion (DRG) neurons innervate visceral structures and undergo hypersensitization in inflammatory models. The characterization of peripheral DRG neuron terminals is an active area of research, but recent work suggests that they communicate with enteroendocrine cells (EECs) in the gut. EECs sense stimuli in the intestinal lumen and communicate information to the brain through hormonal and electrical signaling. In that context, EECs are a target for developing therapeutics to treat visceral pain. Linaclotide is an FDA-approved treatment for chronic constipation that activates the intestinal membrane receptor guanylyl cyclase C (GUCY2C). Clinical trials revealed that linaclotide relieves both constipation and visceral pain. We recently demonstrated that the analgesic effect of linaclotide reflects the overexpression of GUCY2C on neuropod cells, a specialized subtype of EECs. While this brings some clarity to the relationship between linaclotide and visceral analgesia, questions remain about the intracellular signaling mechanisms and neurotransmitters mediating this communication. In this Fundamental Neurochemistry Review, we discuss what is currently known about visceral nociceptors, enteroendocrine cells, and the gut-brain axis, and ongoing areas of research regarding that axis and visceral pain.
摘要：
虽然内脏疼痛通常与肠-脑轴疾病有关，潜在的机制还没有完全理解。背根神经节（DRG）神经元支配内脏结构并在炎症模型中发生超敏反应。周围DRG神经元末端的表征是一个活跃的研究领域，但最近的研究表明，它们与肠道中的肠内分泌细胞（EECs）沟通。EEC感知肠腔中的刺激，并通过激素和电信号将信息传达给大脑。在这种情况下，EEC是开发治疗内脏痛的治疗剂的靶标。利那洛肽是FDA批准的慢性便秘治疗方法，可激活肠膜受体鸟苷酸环化酶C（GUCY2C）。临床试验显示，利那洛肽可以缓解便秘和内脏疼痛。我们最近证明，利那洛肽的镇痛作用反映了GUCY2C对神经足细胞的过度表达，EEC的特殊亚型。虽然这给利那洛肽和内脏镇痛之间的关系带来了一些清晰度，关于细胞内信号机制和介导这种交流的神经递质的问题仍然存在。在这篇《神经化学基础综述》中,我们讨论了目前关于内脏伤害感受器的知识，肠内分泌细胞,和肠-脑轴，以及正在进行的关于轴和内脏疼痛的研究领域。
