Barostat testing of rectal sensation and compliance in humans: comparison of results across two centres and overall reproducibility

American Journal of Physiology-Gastrointestinal and Liver Physi

Kolar

Vázquez-Roque

et al. 2013

P ϭ 0.028). There was significant association of CNR1 rs806378 (P ϭ 0.014; CC vs. CT/TT) with colonic transit in IBS-diarrhea (IBS-D) group; the TT group had the fastest colonic transit at 24 and 48 h. There was significant overall association of CNR1 rs806378 with sensation rating of gas (P ϭ 0.025), but not pain; the strongest associations for gas ratings were in IBS-D (P ϭ 0.002) and IBSalternating (P ϭ 0.025) subgroups. For CNR1 (AAT)n, gene-byphenotype interactions were observed for colonic transit at 24 (P ϭ 0.06) and 48 h (P ϭ 0.002) and gas (P ϭ 0.046, highest for IBS-D, P ϭ 0.034), but not pain sensation; the strongest association with transit was in controls, not in IBS. These data support the hypothesis that cannabinoid receptors may play a role in control of colonic transit and sensation in humans and deserve further study as potential mediators or therapeutic targets in lower functional gastrointestinal disorders.

“…The method and performance characteristics have been extensively described elsewhere (1,7). The focus of the present study was on sensation ratings.…”

Section: Methodsmentioning

confidence: 99%

Cannabinoid receptor 1 gene and irritable bowel syndrome: phenotype and quantitative traits

American Journal of Physiology-Gastrointestinal and Liver Physi

Kolar

Vázquez-Roque

et al. 2013

“…Each distention was maintained for 60 s with an interstimulus interval of 2 min, during which time the balloon was deflated to the baseline operating pressure. The methods and analysis have been described in detail elsewhere (14).…”

Section: Rectal Compliance and Sensation By Barostatmentioning

confidence: 99%

Mitochondrial DNA and gastrointestinal motor and sensory functions in health and functional gastrointestinal disorders

American Journal of Physiology-Gastrointestinal and Liver Physi

Carlson

Zinsmeister³

et al. 2009

Our hypothesis is that these mtDNA SNPs are associated with functional GI disorders (FGIDs) and GI functions. The mt genome was first tested for the 7028C polymorphism (defining haplogroup H) in 699 patients or controls, and those with 7028C were further genotyped at 16519 and 3010. Phenotypes were based on symptoms (validated questionnaires and criteria) and GI physiology using validated motor and sensory studies. Constipation-predominant IBS and alternating constipation and diarrhea IBS are less prevalent in individuals with the 7028C mtDNA polymorphism than in individuals with 7028T. Conversely, 7028C is associated with higher maximum tolerated volume (lower satiation) compared with 7028T. Among those with 7028C, nonspecific abdominal pain (chronic abdominal pain or dyspepsia) was significantly associated with 3010A compared with 3010G (odds ratio 3.3, P ϭ 0.02), and slower gastric emptying was statistically associated with 3010G. There were no significant associations of mtDNA genotypes tested and stomach volumes, small bowel or colonic transit, rectal compliance, and motor or sensory functions. Thus variation in mtDNA may be associated with satiation, gastric emptying, and possibly pain; further studies of mtDNA in appetite regulation and larger numbers of patients with FGIDs are warranted.

“…The method and performance characteristics have been extensively described elsewhere (17,40). Ascending method of limits was used to measure rectal compliance and sensory thresholds.…”

Section: Rectal Compliance and Sensation By Barostatmentioning

confidence: 99%

Candidate genes and sensory functions in health and irritable bowel syndrome

American Journal of Physiology-Gastrointestinal and Liver Physi

Busciglio

Carlson

et al. 2008

Zinsmeister AR. Candidate genes and sensory functions in health and irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol 295: 219 -225, 2008. First published May 29, 2008 doi:10.1152/ajpgi.90202.2008.-Adrenergic and serotonergic (ADR-SER) mechanisms alter gut (GI) function; these effects are mediated through G protein transduction. Candidate genetic variations in ADR-SER were significantly associated with somatic scores in irritable bowel syndrome (IBS) and gastric emptying but not small bowel or colonic transit. Our aim was to assess whether candidate ADR-SER genes are associated with motor and sensory GI functions in IBS and subgroups on the basis of bowel dysfunction. In 122 patients with IBS and 39 healthy controls, we assessed gastrointestinal somatic symptoms and affect by validated questionnaires. We measured: gastric volume (GV), maximum tolerated volume, rectal compliance, sensation thresholds and ratings, and genetic variations including ␣2A (C-1291G), ␣2C (Del 332-325), GN␤3 (C825T), and 5-HTTLPR. Demographics and genotype distributions were similar in the patients with IBS subgrouped on bowel function. There were significant associations between 5-HTTLPR SS genotype and absence of IBS symptoms and between 5-HTTLPR LS/SS genotype and increased rectal compliance and increased pain ratings, particularly at 12 and 24 mmHg distensions. GN␤3 was associated only with fasting GV; we did not detect associations between ␣2A genotype and the gastrointestinal sensory or motor functions tested. We concluded that 5-HTTLPR LS/SS genotype is associated with both increased pain sensation and increased rectal compliance though the latter effect is unlikely to contribute to increased pain sensation ratings with LS/SS genotype. The data suggest the hypotheses that the endophenotype of visceral hypersensitivity in IBS may be partly related to genetic factors, and the association of GN␤3 with fasting GV may explain, in part, the reported association of GN␤3 with dyspepsia. adrenergic; serotonergic; GN␤3; SLC6A4; G protein; receptor ADRENERGIC MECHANISMS alter gastrointestinal reflexes involved in intestinal propulsion, coordinated motor activity in the small bowel and colon, and gastrointestinal tone and fluid secretion (12,46). Norepinephrine is also involved in control of pain including supraspinal inhibition of pain, e.g., due to a change in the behavioral state (37) including stress, which contributes to gut motility disorders (10).Among ␣2 receptors, the ␣2A subtype appears to be critically important for control of motor functions, such as gastrointestinal transit in mice (40) and colonic circular smooth muscle in canine colon (47). The ␣2 receptor agonist, clonidine, inhibits gastric and colonic tone, phasic contractility, and sensation in the rectum and colon in response to balloon distension in healthy humans (4, 43).Serotonergic (5-HT) mechanisms also alter gut absorptive, motor, and sensory functions via actions in the gut, spinal cord, and brain stem (27). Ligand-receptor interaction results in c...