Gas and bloating are common complaints to gastroenterologists, but the pathogenesis of these symptoms is unknown. Research has focused on causes of visceral pain, defining roles for hyperalgesia to visceral pain, defining roles for hyperalgesia to visceral - and mechanoreceptor stimulation. Exaggerated perception is noted curing concurrent chemical and mechanical stimulation showing summation of afferent information. Serotonin (5-HT) modulates gut sensorimotor function via action on neural H-HT and H-HT4 receptors. We hypothesize that patients with gas and bloating exhibit primary defects in visceral afferent responses to small intestinal chemo- and mechanoreceptor stimulation which are differentially regulated by distinct 5-HT pathways. We further hypothesize that these afferent dysfunctions evoke abnormal central nervous system (CNS) processing of sensory information which elicit secondary reflex alterations in intestinal motor patterns thereby promoting pathologic gas retention. We propose comprehensive studies comprising visceral afferent activity, CNS processing of gut sensory information, intestinal motility, and gas retention in patients with gas and bloating with responses in health volunteers. Perception of duodenal nutrient perfusion and intestinal distention will be assessed to determine if patients with gas and bloating exhibit hyperalgesia and to test if hyperalgesia is generalized or specific for individual nutrient subclasses or intestinal regions. Symptoms reports during simultaneous nutrient perfusion and intestinal distention will reveal if patients exhibit more prominent summation to dual afferent stimulation. Perceptual studies will be repeated in the presence of selective 5-HT3 and 5-HT4 antagonists to define 5-HT regulation of visceral perception in each subject groups. Measurement of evoke potentials in response to intestinal stimulation will be performed with and without 5-HT antagonists to characterize spinal afferent function, while brain PET activation patterns will define abnormalities of CNS processing of gut sensory function with gas and bloating. Finally, effects of chemo- and mechanoreceptor stimulation on intestinal motor activity will be quantified and correlated with effects on retention of gas infused into the small intestine We expect that patients with gas and bloating will exhibit hyperalgesia to chemo- and mechanoreceptor stimulation via activation of 5-HT3 and 5-HT4 receptor pathways, respectively, as well as enhanced summation responses which will produce exaggerated spinal and cerebral evoked potentials. This may produce abnormal central nervous system activity which evokes secondary disturbances in intestinal motility resulting in gas retention. The investigation in this proposal will provide novel and significant insight into the mechanisms underlying development of gas and bloating.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
Application #
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Podskalny, Judith M,
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Michigan Ann Arbor
Internal Medicine/Medicine
Schools of Medicine
Ann Arbor
United States
Zip Code
Gonlachanvit, Sutep; Coleski, Radoslav; Owyang, Chung et al. (2006) Nutrient modulation of intestinal gas dynamics in healthy humans: dependence on caloric content and meal consistency. Am J Physiol Gastrointest Liver Physiol 291:G389-95
Coleski, Radoslav; Owyang, Chung; Hasler, William L (2006) Modulation of intestinal gas dynamics in healthy human volunteers by the 5-HT receptor agonist tegaserod. Am J Gastroenterol 101:1858-65
Hasler, William L (2005) Nausea, gastroparesis, and aerophagia. J Clin Gastroenterol 39:S223-9
Coleski, Radoslav; Gonlachanvit, Sutep; Owyang, Chung et al. (2005) Selective reversal of hyperglycemia-evoked gastric myoelectric dysrhythmias by nitrergic stimulation in healthy humans. J Pharmacol Exp Ther 312:103-11
Gonlachanvit, S; Coleski, R; Owyang, C et al. (2004) Inhibitory actions of a high fibre diet on intestinal gas transit in healthy volunteers. Gut 53:1577-82
Coleski, R; Hasler, W L (2004) Directed endoscopic mucosal mapping of normal and dysrhythmic gastric slow waves in healthy humans. Neurogastroenterol Motil 16:557-65
Hasler, William L (2003) The irritable bowel syndrome during pregnancy. Gastroenterol Clin North Am 32:385-406, viii
Hasler, William L (2003) Pharmacotherapy for intestinal motor and sensory disorders. Gastroenterol Clin North Am 32:707-32, viii-ix
Gonlachanvit, Sutep; Chen, Yen Hsueh; Hasler, William L et al. (2003) Ginger reduces hyperglycemia-evoked gastric dysrhythmias in healthy humans: possible role of endogenous prostaglandins. J Pharmacol Exp Ther 307:1098-103
Bjornsson, Einar S; Chey, William D; Hooper, Forrest et al. (2002) Impaired gastrocolonic response and peristaltic reflex in slow-transit constipation: role of 5-HT(3) pathways. Am J Physiol Gastrointest Liver Physiol 283:G400-7

Showing the most recent 10 out of 11 publications