Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Digestive Diseases and Sciences
Published in: Digestive Diseases and Sciences 7/2016

01-07-2016 | DDS-GRG Profiles and Perspectives

Enteric Nervous System: Neuropathic Gastrointestinal Motility

Author: Jackie D. Wood

Published in: Digestive Diseases and Sciences | Issue 7/2016

Login to get access

Excerpt

The enteric nervous system (ENS) is universally acknowledged to be an independent brain-in-the-gut essential for normal motility of the esophagus, stomach, small intestine and colon, as well as for smooth muscle sphincters [1‐3]. As such, the enteric “mini-brain” organizes differing kinds of specialized motility in each of the functionally differentiated compartments along the digestive tract, starting in the esophagus and ending in the recto-sigmoid in humans. My perspective illustrates some of the ways in which neuropathy in the ENS accounts for various forms of disordered motility and their associated pathophysiologic symptoms. …
Literature
1.
Gershon MD. The Second Brain. New York: Harper-Collins; 1998.
2.
Furness JB. The Enteric Nervous System. Oxford: Blackwell; 2006.
3.
Wood JD. Enteric Nervous System: The Brain-in-the-Gut. New Jersey, USA: Morgan & Claypool Life Sciences; 2011.
4.
Brann L, Wood JD. Motility of the large intestine of piebald-lethal mice. Am J Dig Dis. 1976;21:633–640.CrossRefPubMed
5.
Hoffman JM, McKnight ND, Sharkey KA, et al. The relationship between inflammation-induced neuronal excitability and disrupted motor activity in the guinea pig distal colon. Neurogastroenterol Motil. 2011;23:673–682.CrossRefPubMed
6.
Wood JD, Mayer CJ. Patterned discharge of six different neurons in a single enteric ganglion. Pflüg Arch. 1973;338:247–256.CrossRef
7.
Szurszewski JH. A migrating electric complex of canine small intestine. Am J Physiol. 1969;217:1757–1763.PubMed
8.
9.
10.
Code CF. The interdigestive housekeeper of the gastrointestinal tract. Perspect Biol Med. 1979;22:S49–S55.CrossRef
11.
12.
Sarna SK. Giant migrating contractions and their myoelectric correlates in the small intestine. Am J Physiol. 1987;253:G697–G705.PubMed
13.
Mathias JR, Carlson GM, Bertiger G, et al. Migrating action potential complex of cholera: a possible prostaglandin-induced response. Am J Physiol. 1977;232:E529–E534.PubMed
14.
Kamath PS, Phillips SF, O’Connor MK, et al. Colonic capacitance and transit in man: modulation by luminal contents and drugs. Gut. 1990;31:443–449.CrossRefPubMedPubMedCentral
15.
Wood JD. Nonruminant nutrition symposium: neurogastroenterology and food allergies. J Anim Sci. 2012;90:1213–1223.CrossRefPubMed
16.
Wood JD. Effects of bacteria on the enteric nervous system: implications for the irritable bowel syndrome. J Clin Gastroenterol. 2007;41:S7–S19.CrossRefPubMed
17.
Glasgow RE, Mulvihill SJ. Abdominal pain including the acute abdomen. In: Feldman M, Friedman LS, Sleisenger MH, eds. Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management. 7th ed. Philadelphia: Saunders; 2002:71–82.
18.
Grundy D, Al-Chaer ED, Aziz Q, et al. Fundamentals of neurogastroenterology: basic science. Gastroenterology. 2006;130:1391–1411.CrossRefPubMed
19.
Ehrlein HJ. A new technique for simultaneous radiography and recording of gastrointestinal motility in unanesthetized dogs. Lab Anim Sci. 1980;30:879–884.PubMed
20.
Droney J, Ross J, Gretton S, et al. Constipation in cancer patients on morphine. Support Care Cancer. 2008;16:453–459.CrossRefPubMed
21.
Glare P, Walsh D, Sheehan D. The adverse effects of morphine: a prospective survey of common symptoms during repeated dosing for chronic cancer pain. Am J Hosp Palliat Care. 2006;23:229–235.CrossRefPubMed
22.
23.
Wood JD, Galligan JJ. Function of opioids in the enteric nervous system. Neurogastroenterol Motil. 2004;16:17–28.CrossRefPubMed
24.
Sun X, Wang X, Wang GD, et al. Lubiprostone reverses the inhibitory action of morphine on mucosal secretion in human small intestine. Dig Dis Sci. 2011;56:330–338.CrossRefPubMed
25.
Frantzides CT, Cowles V, Salaymeh B, et al. Morphine effects on human colonic myoelectric activity in the postoperative period. Am J Surg. 1992;163:144–148. (discussion 148-9).CrossRefPubMed
26.
Sarna SK, Otterson MF. Small intestinal amyogenesia and dysmyogenesia induced by morphine and loperamide. Am J Physiol. 1990;258:G282–G289.PubMed
27.
Wood JD. Opioids, the enteric nervous system and postoperative ileus. Semin Colon Rectal Surg. 2005;16:188–196.CrossRef
28.
29.
Brown DR, Miller RJ. Adrenergic mediation of the intestinal antisecretory action of opiates administered into the central nervous system. J Pharmacol Exp Ther. 1984;231:114–119.PubMed
30.
Coupar IM, Taylor DA. Evidence for tryptaminergic and noradrenergic involvement in the antisecretory action of morphine in the rat jejunum. J Pharm Pharmacol. 1987;39:363–369.CrossRefPubMed
31.
Jiang Q, Sheldon RJ, Porreca F. Opioid modulation of basal intestinal fluid transport in the mouse: actions at central, but not intestinal, sites. J Pharmacol Exp Ther. 1990;253:784–790.PubMed
32.
Ward SM, Sanders KM. Physiology and pathophysiology of the interstitial cell of Cajal: from bench to bedside. I. Functional development and plasticity of interstitial cells of Cajal networks. Am J Physiol Gastrointest Liver Physiol. 2001;281:G602–G611.PubMed
33.
Huizinga JD. Physiology and pathophysiology of the interstitial cell of Cajal: from bench to bedside. II. Gastric motility: lessons from mutant mice on slow waves and innervation. Am J Physiol Gastrointest Liver Physiol. 2001;281:G1129–G1134.PubMed
34.
Wood JD. Electrical activity from single neurons in Auerbach’s plexus. Am J Physiol. 1970;219:159–169.PubMed
35.
Wood JD. Excitation of intestinal muscle by atropine, tetrodotoxin, and xylocaine. Am J Physiol. 1972;222:118–125.PubMed
36.
Wood JD. Physiology of the enteric nervous system. In: Johnson LR, Alpers DH, Christensen J, Jacobson ED, Walsh JH, eds. Physiology of the Gastrointestinal Tract, vol. 1. 3rd ed. New York: Raven Press; 1994:423–482.
37.
Lennon VA, Sas DF, Busk MF, et al. Enteric neuronal autoantibodies in pseudoobstruction with small-cell lung carcinoma. Gastroenterology. 1991;100:137–142.CrossRefPubMed
38.
Fathallah-Shaykh H, Wolf S, Wong E, et al. Cloning of a leucine-zipper protein recognized by the sera of patients with antibody-associated paraneoplastic cerebellar degeneration. Proc Natl Acad Sci USA. 1991;88:3451–3454.CrossRefPubMedPubMedCentral
39.
Heidenreich F, Schober R, Brinck U, Hartung HP. Multiple paraneoplastic syndromes in a patient with antibodies to neuronal nucleoproteins (anti-Hu). J Neurol. 1995;242:210–216.CrossRefPubMed
40.
King PH, Redden D, Palmgren JS, et al. Hu antigen specificities of ANNA-I autoantibodies in paraneoplastic neurological disease. J Autoimmun. 1999;13:435–443.CrossRefPubMed
41.
De Giorgio R, Bovara M, Barbara G, et al. Anti-HuD-induced neuronal apoptosis underlying paraneoplastic gut dysmotility. Gastroenterology. 2003;125:70–79.CrossRefPubMed
42.
43.
44.
Drossman DA, Li Z, Toner BB, et al. Functional bowel disorders: a multicenter comparison of health status and development of illness severity index. Dig Dis Sci. 1995;40:986–995.CrossRefPubMed
45.
46.
Verne GN, Sallustio JE, Eaker EY. Anti-myenteric neuronal antibodies in patients with achalasia. A prospective study. Dig Dis Sci. 1997;42:307–313.CrossRefPubMed
47.
Törnblom H, Lindberg G, Nyberg B, et al. Full-thickness biopsy of the jejunum reveals inflammation and enteric neuropathy in irritable bowel syndrome. Gastroenterology. 2002;123:1972–1979.CrossRefPubMed
48.
Lindberg G, Törnblom H, Iwarzon M, et al. Full-thickness biopsy findings in chronic intestinal pseudo-obstruction and enteric dysmotility. Gut. 2009;58:1084–1090.CrossRefPubMed
49.
Knowles CH, Veress B, Tornblom H, et al. Safety and diagnostic yield of laparoscopically assisted full-thickness bowel biospy. Neurogastroenterol Motil. 2008;20:774–779.CrossRefPubMed
50.
Törnblom H, Lang B, Clover L, et al. Autoantibodies in patients with gut motility disorders and enteric neuropathy. Scand J Gastroenterol. 2007;42:1289–1293.CrossRefPubMed
51.
Munoz-Garcia D, Ludwin SK. Adult-onset neuronal intranuclear hyaline inclusion disease. Neurology. 1986;36:785–790.CrossRefPubMed
52.
Palo J, Haltia M, Carpenter S, Karpati G, et al. Neurofilament subunit–related proteins in neuronal intranuclear inclusions. Ann Neurol. 1984;15:322–328.CrossRefPubMed
53.
Mayer EA, Schuffler MD, Rotter JI, et al. Familial visceral neuropathy with autosomal dominant transmission. Gastroenterology. 1986;91:1528–1535.CrossRefPubMed
54.
55.
Gershon AA, Chen J, Davis L, et al. Latency of varicella zoster virus in dorsal root, cranial, and enteric ganglia in vaccinated children. Trans Am Clin Climatol Assoc. 2012;123:17–33.PubMedPubMedCentral
56.
Roy AD, Bharucha H, Nevin NC, et al. Idiopathic intestinal pseudo-obstruction: a familial visceral neuropathy. Clin Genet. 1980;18:291–297.CrossRefPubMed
57.
Schuffler MD, Baird HW, Fleming CR, et al. Intestinal pseudo-obstruction as the presenting manifestation of small-cell carcinoma of the lung: a paraneoplastic neuropathy of the gastrointestinal tract. Ann Intern Med. 1983;98:129–134.CrossRefPubMed
58.
Altermatt HJ, Rodriguez M, Scheithauer BW, et al. Paraneoplastic anti-Purkinje and type I anti-neuronal nuclear autoantibodies bind selectively to central, peripheral, and autonomic nervous system cells. Lab Invest. 1991;65:412–420.PubMed
59.
Rosenblum MK. Paraneoplasia and autoimmunologic injury of the nervous system: the anti-Hu syndrome. Brain Pathol. 1993;3:199–212.CrossRefPubMed
60.
Wood JN, Hudson L, Jessell TM, et al. A monoclonal antibody defining antigenic determinants on subpopulations of mammalian neurones and Trypanosoma cruzi parasites. Nature. 1982;296:34–38.CrossRefPubMed
61.
De Giorgio R, Guerrini S, Barbara G, et al. New insights into human enteric neuropathies. Neurogastroenterol Motil. 2004;16:143–147.CrossRefPubMed
62.
De Giorgio R, Guerrini S, Barbara G, et al. Inflammatory neuropathies of the enteric nervous system. Gastroenterology. 2004;126:1872–1883.CrossRefPubMed
63.
De Giorgio R, Ricciardiello L, Naponelli V, et al. Chronic intestinal pseudo-obstruction related to viral infections. Transplant Proc. 2010;42:9–14.CrossRefPubMed
64.
Krishnamurthy S, Schuffler MD. Pathology of neuromuscular disorders of the small intestine and colon. Gastroenterology. 1987;93:610–639.CrossRefPubMed
65.
Smith VV, Gregson N, Foggensteiner L, et al. Acquired intestinal aganglionosis and circulating autoantibodies without neoplasia or other neural involvement. Gastroenterology. 1997;112:1366–1371.CrossRefPubMed
66.
67.
Chen JJ, Gershon AA, Li ZS, et al. Latent and lytic infection of isolated guinea pig enteric ganglia by varicella zoster virus. J Med Virol. 2003;70:S71–S78.CrossRefPubMed
68.
Gershon AA, Chen J, Gershon MD. A model of lytic, latent, and reactivating varicella-zoster virus infections in isolated enteric neurons. J Infect Dis. 2008;197:S61–S65.CrossRefPubMed
69.
Gershon AA, Chen J, Gershon MD. Use of saliva to identify varicella zoster virus infection of the gut. Clin Infect Dis. 2015;61:536–544.CrossRefPubMed
70.
71.
Lundberg I, Nyman U, Pettersson I, et al. Clinical manifestations and anti-(U1)snRNP antibodies: a prospective study of 29 anti-RNP antibody positive patients. Br J Rheumatol. 1992;31:811–817.CrossRefPubMed
72.
Nyman U, Lundberg I, Hedfors E, et al. Recombinant 70-kD protein used for determination of autoantigenic epitopes recognized by anti-RNP sera. Clin Exp Immunol. 1990;81:52–58.CrossRefPubMedPubMedCentral
73.
Ben-Chetrit E, Chan EK, Sullivan KF, et al. A 52-kD protein is a novel component of the SS-A/Ro antigenic particle. J Exp Med. 1988;167:1560–1571.CrossRefPubMed
74.
Peene I, Meheus L, Veys EM, et al. Detection and identification of antinuclear antibodies (ANA) in a large and consecutive cohort of serum samples referred for ANA testing. Ann Rheum Dis. 2001;60:1131–1136.CrossRefPubMedPubMedCentral
75.
Parker JC, Burlingame RW, Bunn CC. Prevalence of antibodies to Ro-52 in a serologically defined population of patients with systemic sclerosis. J Autoimmune Dis. 2009;6:2.CrossRefPubMedPubMedCentral
76.
De Giorgio R, Barbara G, Stanghellini V, et al. Clinical and morphofunctional features of idiopathic myenteric ganglionitis underlying severe intestinal motor dysfunction: a study of three cases. Am J Gastroenterol. 2002;97:2454–2459.CrossRefPubMed
77.
Zhao C, Deng W, Gage FH. Mechanisms and functional implications of adult neurogenesis. Cell. 2008;132:645–660.CrossRefPubMed
78.
Wood JD. Enteric nervous system neuropathy: repair and restoration. Curr Opin Gastroenterol. 2011;27:106–111.CrossRefPubMed
79.
Liu MT, Kuan YH, Wang J, et al. 5-HT4 receptor-mediated neuroprotection and neurogenesis in the enteric nervous system of adult mice. J Neurosci. 2009;29:9683–9699.CrossRefPubMedPubMedCentral
80.
Katsui R, Kojima Y, Kuniyasu H, et al. A new possibility for repairing the anal dysfunction by promoting regeneration of the reflex pathways in the enteric nervous system. Am J Physiol Gastrointest Liver Physiol. 2008;294:G1084–G1093.CrossRefPubMed
81.
Katsui R, Kuniyasu H, Matsuyoshi H, et al. The plasticity of the defecation reflex pathway in the enteric nervous system of guinea pigs. J Smooth Muscle Res. 2009;45:1–13.CrossRefPubMed
82.
Matsuyoshi H, Kuniyasu H, Okumura M, et al. A 5-HT(4)-receptor activation-induced neural plasticity enhances in vivo reconstructs of enteric nerve circuit insult. Neurogastroenterol Motil. 2010;22:e226.CrossRef
83.
Gershon MD, Tack J. The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterology. 2007;132:397–414.CrossRefPubMed
84.
Liu M, Geddis MS, Wen Y, et al. Expression and function of 5-HT4 receptors in the mouse enteric nervous system. Am J Physiol Gastrointest Liver Physiol. 2005;289:G1148–G1163.CrossRefPubMed
85.
Fang X, Liu S, Wang XY, et al. Neurogastroenterology of tegaserod (HTF 919) in the submucosal division of the guinea-pig and human enteric nervous system. Neurogastroenterol Motil. 2008;20:80–93.PubMed
86.
Galligan JJ, Pan H, Messori E. Signalling mechanism coupled to 5-hydroxytryptamine4 receptor-mediated facilitation of fast synaptic transmission in the guinea-pig ileum myenteric plexus. Neurogastroenterol Motil. 2003;15:523–529.CrossRefPubMed
87.
LePard KJ, Ren J, Galligan JJ. Presynaptic modulation of cholinergic and non-cholinergic fast synaptic transmission in the myenteric plexus of guinea pig ileum. Neurogastroenterol Motil. 2004;16:355–364.CrossRefPubMed
88.
Grider JR. Neurotransmitters mediating the intestinal peristaltic reflex in the mouse. J Pharmacol Exp Ther. 2003;307:460–467.CrossRefPubMed
Metadata
Title
Enteric Nervous System: Neuropathic Gastrointestinal Motility
Author
Jackie D. Wood
Publication date
01-07-2016
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 7/2016
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-016-4183-5

Other articles of this Issue 7/2016

Digestive Diseases and Sciences 7/2016 Go to the issue

Editorial

SEMS for Palliation of Malignant Colonic Obstruction: Why SEMi Available Is Not Good Enough

Original Article

Hearing Loss in Patients with Inflammatory Bowel Disease

Correspondence

NOD2 Risk Variants and Pathological Bacterial Translocation in Decompensated Cirrhosis

Original Article

Time to Relapse in Children with Crohn’s Disease Treated with Azathioprine and Nutritional Therapy or Corticosteroids

Original Article

WAVE3 Induces EMT and Promotes Migration and Invasion in Intrahepatic Cholangiocarcinoma

Erratum

Erratum to: Efficacy and Safety of Propofol-Mediated Sedation for Outpatient Endoscopic Retrograde Cholangiopancreatography (ERCP)
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits