Study On The Mechanisms Of Microglial Cells In Visceral Hyperalgesia In Rats With IBS

Background:Irritable bowel syndrome (IBS) is a chronic and intestinal functional diseasewhich is characterized for the recurrent episodes of abdominal pain and bowelhabits change, along with visceral hypersensitivity and gastrointestinal abnormalmovements. However, neurobiological mechanism of IBS has not beencompletely clarified. The latest study shows that microglial cells in centralnervous system widely involve in the visceral pain reaction and may playrelatively important role. According to the previous research conducted by thislaboratory, microglial cells and astrocytes in dorsal commissual nucleus (DCN)have close connection with the visceral hypersensitivity caused by IBS. Moreover,it has been primarily proved that microglial cells play an important role in theearly phase of visceral pain. But the roles of microglial cells in this process andthe ways they participate in the cause and development of visceral hyperalgesiawill play a vital role not only in revealing the neurobiological mechanism of IBS, but also in the research and development of clinical drugs.Objective:Firstly, by using the trichinella gavage method, animal models of IBS in ratsinfected with trichinella spiralis were set up. Secondly, for the purpose ofverifying that microglial cells widely involve in the cause and development ofvisceral pain, expressions of P2X4, P2X7and OX42in dorsal horn of sacralsegment of spinal cord and DCN in rats with irritable bowel syndrome (IBS)induced by the stimulation of colorectal distention are explored, and myoelectricchanges of the rectus abdominis were recorded at the same time. Lastly, based onabove results, by means of scabbard injection of P2X7receptor antagonist,expression of P2X7, OX42, IL-1β, P38and CGRP in dorsal horn of sacralsegment of spinal cord and DCN in rats with IBS induced by the stimulation ofcolorectal distention was explored, which provides a theoretical evidence to theperfection of neurobiological mechanism of IBS and the exploration, researchand development of new clinical drugs.Methods:Using the method of trichinella suspension by gavage, animal models of IBSin rats infected with trichinella spiralis were established. Adopting theelectrophysiological method, myoelectric changes of rectus abdominis of normalrats and IBS rats were observed. By immunofluorescence method, expression ofP2X4, P2X7, OX42, IL-1β, P38and CGRP in dorsal horn of sacral segment ofspinal cord and DCN in the two groups of rats was explored.Results: 1. The electro-activity of the rectus abdominis and expression of P2X4andP2X7receptors of microglial cells in dorsal horn of sacral segment of spinal cordand DCN were significantly enhanced in IBS groups with colon distensioncompared with those in the normal group and non-stimulation IBS group (P<0.01).2. After the intrathecal injection of P2X7receptor antagonist, the stimulationof colorectal distention was conducted, which showed that the expression ofP2X7and OX42in antagonist group dropped significantly compared with colondistension group (P <0.01) and the expression of IL-1β, P38and CGRP, and theelectro-activity of the rectus abdominis, in intervention group also droppedremarkably (P <0.01).ConclusionThe visceral hypersensitivity of IBS not only can lead to the activition ofmicroglial cells in dorsal horn of sacral segment of spinal cord and DCN, but alsomay activate P2X4and P2X7receptors of the microglial cells,which may be animportant target to start microglia signal transduction pathways. Especially, P2X7receptor may be the key to activate microglia cells, and be the molecular biologybasis of visceral hypersensitivity in IBS.