| Irritable Bowel Syndrome (IBS) is one of the most common functional gastrointestinal disorders seen in primary care and gastroenterology practice, with high prevalence rate, difficult treatment and expensive medical cost. The incidence of IBS has been huge increased over the past several decades, but etiology and pathogenesis of it remain unclear, which has an effect on its diagnosis and therapy. Over the years, several theories have been proposed to explain the pathophysiology of IBS, including abnormalities of motility, visceral sensation, inflammation, "brain-gut" interactions and "immune-neuroendocrine network" . Attention has recently been focused on increased perception of visceral stimuli arising from the gastrointestinal tract wall, a phenomenon referred to as visceral hypersensitivity. It is found that with ballon distention studies of the ileum and colorectum, patients with IBS experience awareness of distension and pain at pressures and volumes that are significantly lower than that in control subjects. At least in some cases of IBS, low grade inflammation in the intestinal mucosa has been found in subgroups of patients and may be involved in the pathophysiology of visceral hypersensitivity. Persisting inflammation, resulting from an imbalance of cytokines regulating the inflammatory respones, is one possible mechanism. The elaboration of cytokines is under genetic control. The purpose of this study is to explore the mechanisms of visceral hypersensitivity in IBS by comparing the change of visceralperception to different temperature stimulation rectal distention test and investigating polymorphism of IL-10 gene promoter. 1. The change of visceral sensitivity to intra-rectal different temperature stimulation in patients with irritable bowel syndrome Objective To investigate the pathophysiology of irritable bowel syndrome (IBS) by comparing the change of visceral perception to different temperature stimulation rectal distention test. Methods 21 patients with diarrhea-predominant irritable bowel syndrome (D-IBS), 15 patients with constipation-predominant irritable bowel syndrome (C-IBS) based on Rome II criteria and 33 control subjects were chosen to examine visceral perception. A rectal balloon was inserted into the rectum of the examinees, then the balloon was inflated with 3°C or 35°C water in a random order so as to distend the rectum, the defecation sensation thresholds and abdominal pain thresholds were recorded. Result (1) Despite of the difference of intra-rectal stimuli' s temperature, D-IBS patients and C-IBS patients had lower defecation sensation volume thresholds (DSVT) and abdominal pain volume thresholds (APVT) than the control, respectively, 3°C: DSVT 115.95 + 36. 59ml vs 191. 36 + 56. 60ml, P<0. 05 (D-IBS vs Control) , 133. 00+57. 37ml vs 191. 36 + 56. 60ml, P<0. 05 (C-IBS vs Control), APVT 230. 48 + 74. 53ml vs 348. 33+99. 57ml, P<0. 05(D-IBS vs Control), 241. 00 + 77. 74ml vs 348. 33+99. 57ml, P<0. 05 (C-IBS vs Control) , 35°C: DSVT 89. 29 + 30. 01ml vs 185. 91 + 61.10ml, P<0. 05 (D-IBS vs Control) , 112. 00 +42. 63ml vs 185. 91+61. 10ml, P<0. 05 (C-IBS vs Control), APVT 213. 81 + 78. 72ml vs 346. 79 + 116. 88ml, P<0. 05 (D-IBS vs Control) , 229.00±78. 84ml vs 346. 79±116. 88ml, P<0. 05 (C-IBS vs Control) ; However, no remarkable difference in the defecation sensatin pressure thresholds (DSPT) and abdominal pain pressure thresholds (APPT) was recorded in three groups. (2) Compared with 35 °C stimuli, when inflating with 3°C water both DSVT and DSPT were increased in D-IBS patients (DSVT 115. 95 + 36. 59ml vs 89. 29 + 30. 01ml , P<0. 05, DSPT 56. 43 + 9. 91mmHg vs 51. 24±9. 66mmHg , P<0. 05); only DSVT in C-IBS patients was increased markedly (DSVT 133. 00±57. 37ml vs 112. 00 + 42. 63ml, P <0. 05); However, no remarkable difference was recorded in control groups. (3) The ratio of volume/pressure of both visceral perceptions were lower in IBS group than those in control, but there was no significant difference between D-IBS and C-IBS patients. When inflating with 3°C water the ratio of volume/pressure of defecation sensation was increased in IBS compared with 35°C stimuli. Conclusion(1) There is a significant visceral hypersensitivity in IBS patients.(2) The change of intra-rectal temperature has a remarkable responsibility to thresholds of non-noxious visceral perception in IBS group, but not to noxious ones in IBS and all the sensations in control.(3) IBS patient has a significantly deceased rectal compliance.2. The relationship between interleukin-10 promoter polymorphism and diarrhea-predominant irritable bowel syndromeObjective To investigate whether three diallelic polymorphisms at the position -1082.. -819 and - 592 in the promoter region of the IL-10 gene were associated with diarrhea-predominant irritable bowel syndrome (D-IBS). Methods The IL-10 gene -1082.-819 and -592 positionqpolymorphisms were genotyped by amplification refractory mutation systems-polymerase chain reaction (ARMS-PCR) methods in 43 patients with D-IBS and 41 healthy subjects (HS). Results (1) Compared with HS, D-IBS patients had a greater frequency of T/T genotype at IL-10 gene promoter -819 position (67. 4% vs 39. 0% , P<0. 05), the frequencies of -819 C/T and C/C genotype were not significantly different (23. 3% vs 43. 9% and 9. 3% vs 17. 1%, P>0. 05) ; D-IBS patients also had a greater frequency of -592 A/A genotype compared with HS (67. 4% vs 39. 0% , P <0. 05) ; no significant difference was found in genotype at IL-10 gene promoter -1082 position. (2) The -819 T allele frequency in D-IBS was significantly higher than that in control (79. 1% vs 61. 0% , P<0. 05 ), whereas -819 C allele frequency in D-IBS was lower (20. 9% vs 39. 0% , P<0. 05 ); D-IBS patients also had a greater frequency of -592 A allele compared with HS (79. 1% vs 61. 0% , P<0. 05 ), -592 C allele frequency in D-IBS was lower (20.9% vs 39.0% , P<0.05 ); no significant difference was found in -1082 G or A allele frequency. Conclusions The presence of -819 T/T and -592 A/A genotype may be related to development of D-IBS. SummaryThe purpose of this study was to investigate the mechanisms of visceral hypersensitivity in IBS. The balloon-distension studies of the rectum have shown that patients with IBS experience pain at volumes and pressures that are significantly lower than those that induce pain in control, a phenomenon referred to as visceral hypersensitivity. Theassociation found between D-IBS and IL-10 gene polymorphisms suggestsi n... |
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