The Nerve Fiber Remodeling In The Colon Mucosa Of Irritable Bowel Syndrome Patients And The Relationship Between Nerve Fiber Remodeling And Visceral Hypersensitivity

Background and Objective : Irritable bowel syndrome(IBS)is a functional bowel disorder in which abdominal pain/discomfort is associated with altered defecation and/or bowel habits in absence of demonstrable pathological changes,and the pathophysiological mechanisms of IBS are still unclear.Visceral hypersensitivity is considered as one of the most important mechanisms,which can occur at peripheral and central levels,respectively named as peripheral sensitization and central sensitization.Nerve fiber remodeling plays an important role in the peripheral sensitization.In this article,we investigate the nerve fiber remodeling in sigmoid colon mucosa from IBS with diarrhea(IBS-D)and the relationship between nerve fiber remodeling and visceral hypersensitivity.Materials and Method:IBS-D patients met Rome III criteria were enrolled,healthy subjects and the ulcerative colitis in remission(UCr)patients without symptoms were enrolled as the controls.Questionnaires were applied to evaluate the frequency and degree of abdominal symptoms.Visceral sensitivity was evaluated by the barostat tests in the rectum.Mucosa biopies were obtained from sigmoid colon during colonoscopy.Neuronal marker protein gene product(PGP)9.5-immunoreactive nerve fibers,TRPV1-immunoreactive nerve fibers,nerve growth factor(NGF)and mast cell(MC)in colonic mucosa were quantified through immunohistofluorescence staining with specific antibodies.The histological findings were correlated with barostat tests results by software of SPSS.Results:(1)12 IBS-D patients and 8 UCr patients without symptoms finished the questionnaires.12 IBS-D patients and 6 UCr patients without symptom finished the barostat tests conducted in the rectum.10 IBS-D patients,6 UCr patients without symptom and 4 healthy people finished the colonic mucosa immunohistofluorescence tests.(2)Compared with the UCr patients without symptom,IBS-D patients had lower thresholds for the initial sensation to defecate,the urgency to defecate and the sensation of pain/ discomfort(7.6±3.20 mmHg vs 12.4±4.12 mmHg,P=0.027;16.2±6.27 mmHg vs 23.5±7.07 mmHg,P=0.046;20.9±6.41 mmHg vs 30.6±7.83 mmHg,P=0.011,respectively).(3)Compared with the control group,in IBS-D patients’ sigmoid colon mucosa,the percentage of nerve fibers area(1.4±0.45 vs 0.9±0.25,P=0.047),the TRPV1-immunoreactive nerve fibers in per unit area(4.1(5.32)vs 1.6(2.09),P=0.028),the percentage of the active MC(29(26.8)vs 17(4.9),P=0.028),and the number of cells that can secrete NGF in the mucosa lamina propria stroma(9.0(3.45)vs 4.7(3.09),P=0.047)increased significantly;(4)The percentage of nerve fibers area was significantly correlated to the abdominal pain score(r=0.792,P=0.034,Spearman rank correlation analysis),and the TRPV1-immunoreactive nerve fibers in per unit area were significantly correlated to the threshold for the urgency to defecate(r=-0.9,P=0.037,Spearman rank correlation analysis).Conclusion:(1)IBS-D patients have visceral hypersensitivity,presenting as both allodynia and hyperalgesia.(2)In IBS-D patients’ sigmoid colon mucosa,the numbers of total nerve fibers and the TRPV1-immunoreactive nerve fibers both increased,which may contribute,in part,to the mechanisms of visceral hypersensitivity.(3)In IBS-D patients’ sigmoid colon mucosa,the number of cells that can secrete NGF increased.Besides NGF,there may be other neurotrophins playing an important role in the rectal hypersensitivity;whether MC can secrete NGF remains to be studied further.