Although diverticular disease of the colon (diverticulosis) is a frequent finding in Western countries, its pathophysiologic grounds are still only partially understood. Traditionally considered as an age-related condition, colonic diverticulosis is probably the final result of several factors concurring together to determine the anatomo-functional abnormalities eventually causing outpouching of the viscus’ mucosa. Among these factors, a relevant role seems to be played by an abnormal neuromuscular function of the large bowel, as shown by abnormal myoelectrical and motor function repeatedly described in these patients, as well as by altered visceral perception. These anomalies might be related to the recent demonstration of derangement of enteric innervation (especially involving interstitial cells of Cajal and enteric glial cells), mucosal neuropeptides, and mucosal inflammation. The latter may have a role of paramount importance in the development of visceral hypersensitivity, responsible for abdominal pain in a subset of patients.

Keywords:
Colonic diverticulosis, Pathophysiology, Anatomo-functional abnormalities
1.
Commane DM, Arasaradnam RP, Mills S, Mathers JC, Bradburn M: Diet, ageing and genetic factors in the pathogenesis of diverticular disease. World J Gastroenterol 2009;15:2479–2488.
2.
Stollman N, Raskin JB: Diverticular disease of the colon. Lancet 2004;363:631–639.
3.
Sheth AA, Longo W, Floch MH: Diverticular disease and diverticulitis. Am J Gastronterol 2008;103:1550–1556.
4.
Hall J, Hammerich K, Roberts P: New paradigms in the management of diverticular disease. Curr Probl Surg 2010;47:680–735.
5.
Sandler RS, Everhart JE, Donowitz M, Adams E, Cronin K, Goodman C, Gemmen E, Shah S, Avdic A, Rubin R: The burden of selected digestive diseases in the United States. Gastroenterology 2002;122:1500–1511.
6.
Bassotti G, Villanacci V: Medical treatment of colonic diverticular disease: are we sure the aim is right? Intern Emerg Med 2011, Epub ahead of print.
7.
Simpson J, Scholefield JH, Spiller RC: Pathogenesis of colonic diverticula. Br J Surg 2002;89:546–554.
8.
Bassotti G, Chistolini F, Morelli A: Pathophysiological aspects of diverticular disease of colon and role of large bowel motility. World J Gastroenterol 2003;9:2140–2142.
9.
Parks TG, Connell AM: Motility studies in diverticular disease of the colon. Gut 1969;10:534–542.
10.
Ritchie JA: Movement of segmental constrictions in the human colon. Gut 1971;12:350–355.
11.
Suchowiecky M, Clarke DD, Bhasker M, Perry RJ, Snape WJ Jr: Effect of secoverine on colonic myoelectric activity in diverticular disease of the colon. Dig Dis Sci 1987;32:833–840.
12.
Shafik A, Ahmed I, Shafik AA, El Sibai O: Diverticular disease: electrophysiologic study and a new concept of pathogenesis. World J Surg 2004;28:411–415.
13.
Trotman IF, Misiewicz JJ: Sigmoid motility in diverticular disease and the irritable bowel syndrome. Gut 1988;29:218–222.
14.
Ritsema GH, Thijn CJ, Smout AJ: Motility of the sigmoid in irritable bowel syndrome and colonic diverticulosis. Ned Tijdschr Geneeskd 1990;134:1398–1401.
15.
Cortesini C, Pantalone D: Usefulness of colonic motility study in identifying patients at risk for complicated diverticular disease. Dis Colon Rectum 1991;34:339–342.
16.
Sugihara K, Muto T, Morioka Y: Motility study in right sided diverticular disease of the colon. Gut 1983;24:1130–1134.
17.
Sasaki D, Kido A, Yoshida Y: An endoscopic method to study the relationship between bowel habit and motility of the ascending and sigmoid colon. Gastrointest Endosc 1986;32:185–199.
18.
Leandro PA, Cecconello I, Habr-Gama A, de Olivereira e Silva A, Pontes JF: Gastrointestinal motility in normal subjects and patients with diverticulosis of the colon. Arq Gastroenterol 1984;21:157–163.
19.
Kratzsch KH: Results of electromyography studies of the rectosigmoid. Dtsch Z Verdau Stoffwechselkr 1985;45:45–51.
20.
Katschinski M, Lederer P, Ellermann A, Ganzleben R, Lux G, Arnold R: Myoelectric and manometric patterns of human rectosigmoid colon in irritable bowel syndrome and diverticulosis. Scand J Gastroenterol 1990;25:761–768.
21.
Viebig RG, Pontes JF, Michelsohn NH: Electromanometry of the rectosigmoid in colonic diverticulosis. Arq Gastroenterol 1994;31:135–144.
22.
Parks TG: Rectal and colonic studies after resection of the sigmoid for diverticular disease. Gut 1970;11:121–125.
23.
Smith AN, Kirwan WO, Shariff S: Motility effects of operations performed for diverticular disease. Proc R Soc Med 1974;67:1041–1043.
24.
Landi E, Fianchini A, Landa L, Maniscalco L: Multiple transverse taeniamyotomy for diverticular disease. Surg Gynecol Obstet 1979;148:221–226.
25.
Cortesini C, Bruno L, Pantalone D: Motility effects of anterior resection of the rectum performed for diverticular disease. Ital J Surg Sci 1989;19:369–373.
26.
Correnti FS, Pappalardo G, Mobarhan S, Trentino P, Parenzi GF, Castrini G: Follow-up results of a new colomyotomy in the treatment of diverticulosis. Surg Gynecol Obstet 1983;156:181–186.
27.
Bassotti G, Crowell MD, Whitehead WE: Contractile activity of the human colon: lessons from 24 hour studies. Gut 1993;34:129–133.
28.
Bassotti G, Chiarioni G, Germani U, Battaglia E, Vantini I, Morelli A: Endoluminal instillation of bisacodyl in patients with severe (slow transit type) constipation is useful to test residual colonic propulsive activity. Digestion 1999;60:69–73.
29.
Camilleri M, Bharucha AE, di Lorenzo C, Hasler WL, Prather CM, Rao SS, Wald A: American Neurogastroenterology and Motility Society consensus statement on intraluminal measurement of gastrointestinal and colonic motility in clinical practice. Neurogastroenterol Motil 2008;20:1269–1282.
30.
Bassotti G, Battaglia E, Spinozzi F, Pelli MA, Tonini M: Twenty-four hour recordings of colonic motility in patients with diverticular disease: evidence for abnormal motility and propulsive activity. Dis Colon Rectum 2001;44:1814–1820.
31.
Bassotti G, Betti C, Imbimbo BP, Pelli MA, Morelli A: Colonic motor response to eating: a manometric investigation in proximal and distal portions of the viscus in man. Am J Gastroenterol 1989;84:118–122.
32.
Narducci F, Bassotti G, Gaburri M, Morelli A: Twenty four hour manometric recording of colonic motor activity in healthy man. Gut 1987;28:17–25.
33.
Bassotti G, Gaburri M: Manometric investigation of high-amplitude propagated contractile activity of the human colon. Am J Physiol 1988;255:G660–G664.
34.
García-Olmo D, Sanchez PC: Patterns of colonic motility as recorded by a sham fecaloma reveal differences among patients with idiopathic chronic constipation. Dis Colon Rectum 1998;41:480–489.
35.
Brann L, Wood JD: Motility of the large intestine of piebald-lethal mice. Am J Dig Dis 1976;21:633–640.
36.
Bassotti G, Battaglia E, De Roberto G, Morelli A, Tonini M, Villanacci V: Alterations in colonic motility and relationship to pain in colonic diverticulosis. Clin Gastroenterol Hepatol 2005;3:248–253.
37.
Clemens CH, Samsom M, Roelofs J, van Berge Henegouwen GP, Smout AJ: Colorectal visceral perception in diverticular disease. Gut 2004;53:717–722.
38.
Whiteway J, Morson BC: Pathology of the ageing – diverticular disease. Clin Gastroenterol 1985;14:829–846.
39.
Smith AN: Colonic muscle in diverticular disease. Clin Gastroenterol 1986;15:917–935.
40.
Golder M, Burleigh DE, Ghali L, Feakins RM, Lunniss PJ, Williams NS, Navsaria HA: Longitudinal muscle shows abnormal relaxation responses to nitric oxide and contains altered levels of NOS1 and elastin in uncomplicated diverticular disease. Colorectal Dis 2007;9:218–228.
41.
Huizinga JD: Electrophysiology of human colon motility in health and disease. Clin Gastroenterol 1986;15:879–901.
42.
Huizinga JD, Waterfall WE, Stern HS: Abnormal response to cholinergic stimulation in the circular muscle layer of the human colon in diverticular disease. Scand J Gastroenterol 1999;34:683–688.
43.
Liu L, Shang F, Markus I, Burcher E: Roles of substance P receptors in human colon circular muscle: alterations in diverticular disease. J Pharmacol Exp Ther 2002;302:627–635.
44.
Burcher E, Shang F, Warner FJ, Du Q, Lubowski DZ, King DW, Liu L: Tachykinin NK2 receptor and functional mechanisms in human colon: changes with indomethacin and in diverticular disease and ulcerative colitis. J Pharmacol Exp Ther 2008;324:170–178.
45.
Guagnini F, Valenti M, Mukenge S, Matias I, Bianchetti A, Di Palo S, Ferla G, Di Marzo V, Croci T: Neural contractions in colonic strips from patients with diverticular disease: role of endocannabinoids and substance P. Gut 2006;55:946–953.
46.
Tomita R, Tanjoh K, Fujisaki S, Fukuzawa M: Physiological studies on nitric oxide in the right sided colon of patients with diverticular disease. Hepatogastroenterology 1999;46:2839–2844.
47.
Tomita R, Fujisaki S, Tanjoh K, Fukuzawa M: Role of nitric oxide in the left-sided colon of patients with diverticular disease. Hepatogastroenterology 2000;47:692–696.
48.
Grider JR, Cable MB, Bitar KN, Said SI, Makhlouf GM: Vasoactive intestinal peptide. Relaxant neurotransmitter in tenia coli of the guinea pig. Gastroenterology 1985;89:36–42.
49.
Milner P, Crowe R, Kamm MA, Lennard-Jones JE, Burnstock G: Vasoactive intestinal polypeptide levels in sigmoid colon in idiopathic constipation and diverticular disease. Gastroenterology 1990;99:666–675.
50.
Jeyarajah S, Papagrigoriadis S: Review article: the pathogenesis of diverticular disease – current perspectives on motility and neurotransmitters. Aliment Pharmacol Ther 2011;33:789–800.
51.
Banerjee S, Akbar N, Moorhead J, Rennie JA, Leather AJ, Cooper D, Papagrigoriadis S: Increased presence of serotonin-producing cells in colons with diverticular disease may indicate involvement in the pathophysiology of the condition. Int J Colorectal Dis 2007;22:643–649.
52.
Costedio MM, Coates MD, Danielson AB, Buttolph TR 3rd, Blaszyk HJ, Mawe GM, Hyman NH: Serotonin signaling in diverticular disease. J Gastrointest Surg 2008;12:1439–1445.
53.
Simpson J, Sundler F, Humes DJ, Jenkins D, Scholefield JH, Spiller RC: Post inflammatory damage to the enteric nervous system in diverticular disease and its relationship to symptoms. Neurogastroenterol Motil 2009; 21:e847–e858.
54.
Vuong NP, Sezeur A, Balaton A, Malafosse M, Camilléri JP: Myenteric plexuses and colonic diverticulosis: results of a histological study. Gastroenterol Clin Biol 1985;9:434–436.
55.
Stoss F, Meier-Ruge W: Experience with neuronal intestinal dysplasia (NID) in adults. Eur J Pediatr Surg 1994;4:298–302.
56.
Iwase H, Sadahiro S, Mukoyama S, Makuuchi H, Yasuda M: Morphology of myenteric plexuses in the human large intestine: comparison between large intestines with and without colonic diverticula. J Clin Gastroenterol 2005;39:674–678.
57.
Deduchovas O, Saladzinskas Z, Tamelis A, Pavalkis D, Pauziene N, Pauza DH: Morphologic pattern of myenteric neural plexus in colonic diverticular disease. A whole-mount study employing histochemical staining for acetylcholinesterase. Ann Anat 2008;190:525–530.
58.
Oh HE, Chetty R: Intramucosal ganglion cells are common in diverticular disease. Pathology 2008;40:470–474.
59.
Bassotti G, Villanacci V, Salerni B, Maurer CA, Cathomas G: Beyond hematoxylin and eosin: the importance of immunohistochemical techniques for evaluating surgically resected constipated patients. Tech Coloproctol 2011;15:371–375.
60.
Bassotti G, Battaglia E, Bellone G, Dughera L, Fisogni S, Zambelli C, Morelli A, Mioli P, Emanuelli G, Villanacci V: Interstitial cells of Cajal, enteric nerves, and glial cells in colonic diverticular disease. J Clin Pathol 2005;58:973–977.
61.
Becheanu G, Manuc M, Dumbravă M, Herlea V, Hortopan M, Costache M: The evaluation of interstitial Cajal cells distribution in non-tumoral colon disorders. Rom J Morphol Embryol 2008;49:351–355.
62.
Wedel T, Büsing V, Heinrichs G, Nohroudi K, Bruch HP, Roblick UJ, Böttner M: Diverticular disease is associated with an enteric neuropathy as revealed by morphometric analysis. Neurogastroenterol Motil 2010;22:407–414.
63.
Quigley EM. What we have learned about colonic motility: normal and disturbed. Curr Opin Gastroenterol 2010;26:53–60
64.
Bassotti G, Villanacci V: Can ‘functional’ constipation be considered as a form of enteric neuro-gliopathy? Glia 2011;59:345–350.
© 2012 S. Karger AG, Basel
2012
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.