Abnormalities in the contractile properties of colonic smooth muscle in idiopathic slow transit constipation

Slater, Bethany J.; Varma, J. S.; Gillespie, James

doi:10.1002/bjs.1800840211

Cited by 13 publications

(10 citation statements)

References 16 publications

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“…Hypersensitivity to cholinergic stimulation has previously been demonstrated in colonic smooth muscle from patients with idiopathic slow transit constipation and it was suggested that this might be explained by the development of a secondary denervation hypersensitivity 18 . This explanation is in keeping with abnormalities known to exist in the myenteric plexus of these patients and supported by the finding of a functional cholinergic deficit in response to electrical stimulation of the myenteric plexus 19 , .…”

Section: Discussionmentioning

confidence: 66%

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Abnormal contractile properties of rectal smooth muscle in chronic ulcerative colitis

Cook

Brading

Mortensen

2000

Aliment Pharmacol Ther

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Background: Patients with ulcerative colitis have abnormal rectal motility. Aim: To compare the contractile properties of rectal smooth muscle from patients with ulcerative colitis and controls. Methods: Rectal smooth muscle strips from patients undergoing resection for ulcerative colitis or cancer (control) were mounted in an organ bath. The effects of carbachol (receptor–mediated) and potassium (causes membrane depolarization) were studied. Acetylcholinesterase histochemistry was performed and nerve counts compared. Results: Ulcerative colitis (n=41) and control (n=34) strips contracted in response to potassium and carbachol. Mean (S.E.M.) maximum response to potassium in the control and ulcerative colitis groups was 1.07 (0.06) g/mg and 1.02 (0.09) g/mg tissue, respectively (P=N.S.). EC50s (concentrations required to give 50% of maximal response) were 75 (1) mM and 73 (1) mM, respectively (P=N.S.). Although maximum responses to carbachol were similar, 2.12 (0.12) g/mg and 1.95 (0.12) g/mg tissue (P=N.S.), ulcerative colitis strips exhibited an increased sensitivity to carbachol, EC50s: 5.05 × 10–6 (0.55 × 10–6) M vs. 8.36 × 10–6 (0.88 × 10–6) M, P=0.002). There was no significant difference in nerve counts between the tissues, as assessed by staining for acetylcholinesterase. Conclusions: Ulcerative colitis tissue has an increased sensitivity to carbachol and this is not due to denervation; it may result from increased calcium release from intracellular stores since contraction due to membrane depolarization is not altered. Modulation of this pathway could potentially be used to alter rectal motility in patients with ulcerative colitis.

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Section: Discussionmentioning

confidence: 66%

“…Organ bath experiments are a robust and well established means of assessing smooth muscle function 16 –18 . Contractile responses of rectal smooth muscle to carbachol and potassium are well recognized and similar responses to each were observed in both ulcerative colitis and cancer strips.…”

Section: Discussionmentioning

confidence: 99%

Abnormal contractile properties of rectal smooth muscle in chronic ulcerative colitis

Cook

Brading

Mortensen

2000

Aliment Pharmacol Ther

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“…This assumption is also supported by physiological data in-vivo where ambulatory 24 hour colonic manometry showed features suggestive of a myopathy in 24% of select patients with STC [84]. It is supported by some in-vitro data from organ bath studies of colonic muscle strips from patients with constipation [78, 83] but not by others [85]. Despite this, there is remarkably little known about myopathies in chronic idiopathic constipation and slow transit constipation at a tissue level.…”

Section: Myopathymentioning

confidence: 67%

“…There are several reports of significantly decreased [46, 50,81,82]; or increased [49] immunohistochemical densities of nerve structures (variably described as nerve fibres, enteric neurofilaments and small axonal fibres) as determined by subjective or automated counting methods. While these changes may have potential pathophysiological importance [83], aside from the contradictory nature of findings, there are no current standardized methods or robust normative data to render diagnostic utility to such measurements.…”

Section: Neuropathymentioning

confidence: 99%

Gastrointestinal neuromuscular pathology in chronic constipation

Knowles

Farrugia

2011

Best Practice & Research Clinical Gastroenterology

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Some patients with chronic constipation may undergo colectomy yielding tissue appropriate to diagnosis of underlying neuromuscular pathology. The analysis of such tissue has, over the past 40 years, fuelled research that has explored the presence of neuropathy, myopathy and more recently changes in interstitial cells of Cajal (ICC). In this chapter, the data from these studies have been critically reviewed in the context of the significant methodological and interpretative issues that beset the field of gastrointestinal neuromuscular pathology. On this basis, reductions in ICC appear to a consistent finding but one whose role as a primary cause of slow transit constipation requires further evaluation. Findings indicative of significant neuropathy or myopathy are variable and in many studies subject to considerable methodological bias. Methods with practical diagnostic utility in the individual patient have rarely been employed and require further validation in respect of normative data.

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“…Most myopathies are characterized by intestinal dilatation (pseudo‐obstruction), although some patients present with constipation. Consistent findings have not been demonstrated by light microscopy in patients with STC5, 6, and in vitro physiological studies have produced conflicting results11, 12. Morphological changes seen in intestinal myopathies include varying degrees of fibrosis, hypertrophy or atrophy of muscle fibres, vacuolation of myocytes9, 13, 14, alteration in the immunohistochemical staining patterns of myocyte contractile proteins15, abnormal layering of the muscle9, and the presence of intracellular inclusion bodies14.…”

Section: Introductionmentioning

confidence: 98%

Smooth muscle inclusion bodies in slow transit constipation

et al. 2001

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Slow transit constipation (STC) is a disorder of intestinal motility of unknown aetiology. Myopathies, including those characterized by the finding of inclusion bodies, have been described in enteric disorders. Amphophilic inclusion bodies have been reported in the muscularis externa of the colon of STC patients. This study formally tested the hypothesis that these represent a primary muscle disorder, specific to STC. In a systematic, blinded, dual observer qualitative and quantitative analysis, colonic and ileal tissue from patients with STC (n=36) were compared with selected control populations: total colonic aganglionosis (n=10), Chagas' disease (n=6), isolated rectal evacuation disorders (n=6), and a control population of a range of ages (n=80). All sections were stained with haematoxylin and eosin and periodic acid Schiff. Further immunostains were used in an attempt to determine inclusion body composition. Round or ovoid (4-22 microm diameter) amphophilic inclusions increased in number in normal subjects with age. Inclusions were more frequent in idiopathic STC than in age-matched controls or rectal evacuation disorders [ileum (33% vs. 9%), ascending (50% vs. 19%, p<0.05), and sigmoid colon (43% vs. 20%)] and were very frequent in the sigmoid (71%) of patients with STC arising after pelvic surgery. The number of inclusions per unit area was significantly higher in patients with STC (p<0.001). Inclusions were found in all Chagas' patients, but not with aganglionosis. It was not possible to determine inclusion body composition, despite the use of a wide range of conventional and immunostains. This study demonstrates that inclusion body myopathy is identifiable in patients with STC and that it may arise secondary to denervation.

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Abnormalities in the contractile properties of colonic smooth muscle in idiopathic slow transit constipation

Abstract: These findings indicate that colonic smooth muscle from patients with ISTC is hypersensitive to cholinergic stimulation and suggest the existence of a smooth muscle myopathy in this condition.

Cited by 13 publications

References 16 publications

Abnormal contractile properties of rectal smooth muscle in chronic ulcerative colitis

Abnormal contractile properties of rectal smooth muscle in chronic ulcerative colitis

Gastrointestinal neuromuscular pathology in chronic constipation

Smooth muscle inclusion bodies in slow transit constipation

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