Fundamental Neurochemistry Review: The role of enteroendocrine cells in visceral pain

In this Fundamental Neurochemistry Review, we discuss the novel interaction between enteroendocrine cells (EECs) and spinal afferent nociceptors and their role in visceral pain. We focus on the role of the intestinal membrane receptor guanylyl cyclase C (GUCY2C) in visceral nociception and its potential as a therapeutic target. AbstractWhile 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-a pproved 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 overexpressio n 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 intrace...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: REVIEW Source Type: research