Role of chemical stimulation of the duodenum in dyspeptic symptom generation.
The response to chemical stimuli such as acid, nutrients, and capsaicin at the level of the duodenum is increasingly recognized as important in the etiology of dyspeptic symptoms. Increased duodenal acid exposure has been reported for patients with dyspeptic symptoms. Duodenal hypersensitivity to acid and the enhancing effect of duodenal acid on gastroduodenal mechanosensitivity may also contribute to dyspeptic symptom generation. Serotonergic signaling pathways may be involved in acid-induced dyspeptic symptoms. As for nutrients, lipid has been unequivocally shown to have a function in the pathogenesis of dyspeptic symptoms. Cholecystokinin (CCK) is an important mediator of the effects of duodenal lipid on gastroduodenal sensorimotor activities. It is unclear whether CCK hypersecretion or hypersensitivity to CCK is responsible for symptoms in dyspeptic patients. The presence of capsaicin in the duodenum evokes symptoms and affects gastric sensorimotor function. In patients with dyspepsia, capsaicin-induced symptoms appeared to occur earlier and to be more severe, however the effects of duodenal infusion and putative consequent gastric sensorimotor abnormalities have not been examined. Capsaicin activates transient receptor potential ion channel of the vanilloid type I, which can also be activated and sensitized by acid. The interaction between the different chemical stimuli is complex and has not yet been studied in patients with dyspeptic symptoms. In conclusion, the mechanisms underlying an enhanced response to duodenal chemical stimulation in patients with dyspeptic symptoms are partially understood. At the level of the duodenum, abnormalities may exist in stimulus intensity, mucosal mRNA expression, biosynthesis, release, or inactivation of mucosal mediators, or receptor expression on afferent nerve endings. Elucidation of the abnormalities involved will provide a basis for rational treatment of dyspeptic symptoms.
van Boxel
O S
OS
Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands. o.s.vanboxel@umcutrecht.nl
ter Linde
J J M
JJ
Siersema
P D
PD
Smout
A J P M
AJ
D002211:Capsaicin / Q000009:adverse effects; D004040:Dietary Carbohydrates / Q000009:adverse effects; D004386:Duodenum / Q000187:drug effects* / Q000503:physiopathology; D004415:Dyspepsia / Q000139:chemically induced* / Q000145:classification / Q000503:physiopathology; D005744:Gastric Acid; D006801:Humans; D008055:Lipids / Q000009:adverse effects
D004040:Dietary Carbohydrates; D008055:Lipids; D002211:Capsaicin