Biopsy specimens of descending colon from patients with IBS showed an increase in mast cells displaying features of degranulation and increased tryptase compared with healthy subjects (151). The study also showed a correlation between the vicinity of mast cells to nerves and the severity and frequency of perceived abdominal pain sensations (151). These data support a possible role of mast cells as effector cells in the visceral nociception in IBS patients. In experimental animals, the mast cell stabilizer, doxantraxoze, which has no effect by itself on the visceral response to rectal distension, suppressed stress-induced hyperalgesia in rats (39). Other reports demonstrate that acute restraint stress degranulates colonic mucosal mast cells through autonomic-dependent pathways, as shown by the increased release of mucosal protease II and histamine in the rat colon (39,40,151-153). In addition, visceral hyperalgesia can be reproduced by peripheral injection of mast cell degradulator, BrX-537 (154). Anatomical support for neurally mediated activation of colonic mucosal mast cells by restraint stress in rats (155) came from anatomical investigation showing that one-half to two-thirds of mast cells are closely apposed to nerves in the intestinal mucosa (156). Mast cell mediators such as tryp-tase, through activation of protease-activated receptor-2 receptors located on enteric nerves and visceral afferents (157), can induce a delayed hyperalgesia in response to CRD (157,158). Other mediators released from rat mast cells, namely, prostaglandins and serotonin, unlike histamine, may also contribute to the alteration of visceral sensory information (40,154,159,160).
Stress-induced activation of colonic mast cells is consistent with the involvement of brain CRF/CRF receptor-signaling pathways. First, CRF injected ICV mimicked the effects of acute stress by inducing mast cell degranulation and increasing histamine content in the rat colon (153,155). Second, ICV injection of CRF antagonist, a-helical CRF9-41, blocked restraint-induced mucosal mast cell activation and increased histamine content in the colon (153,155). Lastly, central injection of CRF induced a CRF1-mediated alteration of autonomic regulation of colonic secretory and motor function (15). These data support a brain CRF receptor-mediated intestinal mucosal mast cell degranulation induced by restraint stress.
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