Bowel Physiology - normal and otherwise
A compilation of articles recently gleaned from the Internet by Mike
D’Orazio, ET, January 2006.
http://www.emedicine.com/ped/topic1203.htm
Pathophysiology: The normal bowel contains gas as well as chyle, which is the sum of
food and salivary, gastric, biliary, pancreatic, and intestinal secretions. Chyle continues to
accumulate, even without oral intake. Intrinsic or extrinsic blockage of the small bowel
leads to accumulating secretions that dilate the intestine proximal to the lesion.
Increased peristaltic contractions and intraluminal pressure may cause frequent loose
stools and flatus early in the disease course. Vomiting also occurs in proximal
obstructions. Intestinal absorption and lymphatic drainage decrease if intraluminal
pressure exceeds capillary and venous pressure in the bowel wall.
The bowel becomes ischemic when capillary blood flow stops, allowing bacteria to enter
the blood stream and septicemia to develop. Perforation can develop as the ischemia
leads to bowel necrosis. Massive third spacing of fluids rapidly leads to shock,
contributing to morbidity and mortality. This sequence may occur more rapidly in a
closed-loop obstruction with no proximal escape for bowel contents.
Am J Surg. 1995 Mar;169(3):294-9.
Related Articles, Links
Amelioration of intestinal dysmotility and stasis by octreotide early
after small-bowel autotransplantation in dogs.
Nakada K, Ikoma A, Suzuki T, Reynolds JC, Campbell WL, Todo S, Starzl
TE.
Department of Surgery, Pittsburgh Transplantation Institute, University of
Pittsburgh, School of Medicine.
BACKGROUND: Intestinal dysmotility and stasis after intestinal transplantation
are considered to promote bacterial overgrowth and translocation. Two prokinetic
agents, KW5139 (13-leu-motilin) and the somatostatin analogue octreotide
acetate, were studied to determine whether they can ameliorate intestinal
dysmotility during the early postoperative period. MATERIALS AND
METHODS: Motility was recorded by multiple extraluminal strain-gauge
transducers in 6 dogs on postoperative days 1, 3, 7, and 14. A barium meal study
was performed with a separate group of 8 dogs on postoperative days 3 and 7.
RESULTS: The agent KW5139 induced brief, weak contractions in the graft and
1
had little effect on the dilated bowel; however, octreotide induced motor activity
that propelled accumulated intestinal contents into the colon and reduced dilation
of the transplanted bowel. CONCLUSION: Octreotide, but not KW5139,
ameliorates intestinal dysmotility associated with bowel autotransplantation
during the early postoperative period. Short-term administration of octreotide may
be useful for the treatment of dysmotility following intestinal transplantation.
http://gastroresource.com/GITextbook/en/chapter7/7-2.htm
2. Small Intestinal Motility
page 184
The main function of the small intestine is digestion and absorption of nutrients. In this process,
the role of small bowel motility is to mix food products with the digestive enzymes, to promote
contact of chyme with the absorptive cells over a sufficient length of bowel and finally to propel
remnants into the colon. Well-organized motility patterns occur in the small intestine to
accomplish these goals in the fed as well as the fasting state. During fasting, a migrating motor
complex (MMC) exists. This complex is characterized by a front of intense spiking activity (phase
III activity) that migrates down the entire small intestine; as the front reaches the terminal ileum,
another front develops in the gastroduodenal area and progresses down the intestine. The
purpose of this phase III myoelectric and contractile activity is to sweep remnants of the previous
meal into the colon and prevent stagnation and bacterial overgrowth. The MMC often starts in the
lower esophagus. Sweeping through the stomach, it removes debris and residual material not
emptied with the last meal. Absence of phase III activity is associated with bacterial overgrowth
and diarrhea. Thus, the small bowel is active even during fasting.
During meals, this cycle is interrupted and the motility pattern in the small bowel becomes an
irregular spiking activity called the fed pattern. This fed pattern of motility does not seem to move
intestinal contents forward to any great extent but does mix these contents with digestive juices,
spreading them again and again over the absorptive surface of the brush border. Diarrhea can
thus occur when this normal fed pattern is replaced by aggressive propulsive contractions.
http://gastroresource.com/GITextbook/en/chapter7/7-17.htm
page 251
17. Bacterial Overgrowth Syndrome
The bacterial overgrowth syndrome can result from any disease that interferes with the normal
balance (ecosystem) of the small intestinal flora and brings about loss of gastric acidity; alteration
in small bowel motility or lesions predisposing to luminal stasis; loss of the ileocecal valve; or
overwhelming contamination of the intestinal lumen (Table 16).
The bacterial overgrowth syndrome gives rise to clinical abnormalities arising from the
pathophysiological effects on the luminal contents and the mucosa. Bacteria can consume
proteins and carbohydrates. In bacterial overgrowth there may be defective transport of sugars,
possibly related to the toxic effect of deconjugated bile acids.
TABLE 16. Etiology of the bacterial overgrowth syndrome
Breakdown of normal defense mechanisms
Achlorhydria
Stasis:

Anatomic (Crohn's disease, diverticula, lymphoma, strictures)
2

Functional (scleroderma, diabetic autonomic neuropathy, pseudo-obstruction)
Loss of ileocecal valve
Contamination
Postinfection
Enteroenteric fistulas, gastrocolic fistulas
Steatorrhea results from the deconjugation and dehydroxylation of bile acids; lithocholic acid is
precipitated and free bile acids are reabsorbed passively, making them unavailable and incapable
of performing micellar solubilization. There may also be mucosal damage. Fats, cholesterol and
fat-soluble vitamins are malabsorbed. Vitamin B12 is also malabsorbed as a result of the binding
and incorporation of this vitamin into the bacteria. Folate deficiency, however, is not a common
occurrence in bacterial overgrowth; unlike vitamin B12, folate synthesized by microorganisms in
the small bowel is available for host absorption. In patients with small bowel bacterial overgrowth,
serum folate levels tend to be high rather than low. The enteric bacteria also produce vitamin K,
and patients with bacterial overgrowth who are on the anticoagulant warfarin may have difficulty
in maintaining the desired level of anticoagulation. In addition to steatorrhea, patients with
bacterial overgrowth frequently complain of watery diarrhea. Important mechanisms in producing
this diarrhea include (1) disturbances of the intraluminal environment with deconjugated bile
acids, and hydroxylated fatty and organic acids; and (2) direct changes in gut motility.
In some patients, symptoms of the primary disease predominate, and evidence of bacterial
overgrowth may be found only on investigation. In others, the primary condition is symptomless,
and the patient presents with a typical malabsorption syndrome due to bacterial overgrowth
(Table 17).
TABLE 17. Diagnosis of the bacterial overgrowth syndrome
Jejunal culture
Tests of bile salt deconjugation
14C-glycocholate breath tests
In vitro deconjugation assessment
Tests of malassimilation
Vitamin B12 (Schilling test)
D-xylose, glucose, lactulose
H2 breath tests
Once diagnosis of bacterial overgrowth is suspected a careful history should be performed to
identify possible causes. Physical examination may be normal or may demonstrate signs related
to specific nutrient deficiencies.
A small bowel biopsy is of value in excluding primary mucosal disease as the cause of the
malabsorption. Histologic abnormalities of the jejunal mucosa are usually not seen in patients
with bacterial overgrowth. The sine qua non for the diagnosis of bacterial overgrowth is a properly
collected and appropriately cultured aspirate of the proximal small intestine. Specimens should be
obtained under anaerobic conditions and quantitative colony counts determined. Generally,
bacteria concentrations of greater than 105 organisms per mL are highly suggestive of bacterial
overgrowth. Such methods are difficult and usually undertaken only in a research setting.
Alternatively, one can attempt to demonstrate a metabolic effect of the bacterial overgrowth, such
as intraluminal bile acid deconjugation by the bile acid or 14C-glycocholate breath test.
Cholylglycine-14C (glycine-conjugated cholic acid with the radiolabeled 14C on the glycine moiety)
3
when ingested circulates normally in the enterohepatic circulation without deconjugation.
Bacterial overgrowth within the small intestine splits the 14C-labeled glycine moiety and
subsequently oxidizes it to 14C-labeled CO2, which is absorbed in the intestine and exhaled.
Excess 14CO2 appears in the breath. The bile acid breath test cannot differentiate bacterial
overgrowth from ileal damage or resection where excessive breath 14CO2 production is due to
bacterial deconjugation within the colon of unabsorbed 14C-labeled glycocholate. This creates
clinical difficulties, since bacterial overgrowth may be superimposed on ileal damage in such
conditions as Crohn's disease.
Breath hydrogen analysis allows a distinct separation of metabolic activity of intestinal flora of the
host, since no hydrogen production is known to occur in mammalian tissue. Excessive and early
breath hydrogen production has been noted in patients with bacterial overgrowth following the
oral administration of either 50 g of glucose or 10 g of lactulose.
Another hallmark of bacterial overgrowth is steatorrhea, detected by the 72-hour fecal fat
collection.
The Schilling test also is abnormal. 57Co-B12 is given with intrinsic factor following a flushing dose
of nonradioactive B12 given parenterally to prevent tissue storage of the labeled vitamin. In
healthy subjects, 57Co-B12 combines with intrinsic factor and is absorbed and >8% excreted in the
urine within 24 hours. In patients with bacterial overgrowth, the bacteria combine with or destroy
intrinsic factor, the vitamin or both, causing decreased vitamin B12 absorption. Following
treatment with antibiotics the B12 absorption returns to normal.
Treatment of bacterial overgrowth involves removing the cause, if possible. The addition of a
broad-spectrum antibiotic (tetracycline 250 mg q.i.d., often accompanied by metronidazole 250
mg q.i.d., for 10 days) will often induce a remission for many months. If the cause cannot be
eliminated and symptoms recur, good results can be achieved with intermittent use of antibiotics
(e.g., one day a week, or one week out of every six).
http://journal.diabetes.org/clinicaldiabetes/V18N42000/pg148.htm
Diabetes and the Gastrointestinal Tract
James D. Wolosin, MD, FACP, and Steven V. Edelman, MD
The Small Intestine in Diabetes
In some cases of longstanding diabetes, the enteric nerves supplying the small intestine
may be affected, leading to abnormal motility, secretion, or absorption. This leads to
symptoms such as central abdominal pain, bloating, and diarrhea. Delayed emptying and
stagnation of fluids in the small intestine may lead to bacterial overgrowth syndromes,
resulting in diarrhea and abdominal pain.
Metclopropamide and cisapride may help to accelerate the passage of fluids through the
small intestine, whereas broad-spectrum antibiotics will decrease bacterial levels.
Diagnosis can be quite difficult and may require small-bowel intubation for quantitative
small-bowel bacterial cultures. Breath hydrogen testing and the [14C]-D-xylose test may
be helpful in diagnosing bacterial overgrowth as well. All of these tests are somewhat
4
cumbersome, and an empiric trial of antibiotics is often the most efficient means of
diagnosing and treating this condition.
Numerous antibiotic regimens have been shown to be effective, including 5- to 10-day
courses of tetracycline, ciprofloxin, amoxacillin, or tetracycline. A short course may
provide prolonged relief, but typically, additional courses of antibiotics are required when
symptoms recur in several weeks or months.
At times, enteric neuropathy may lead to a chronic abdominal pain syndrome similar to
the pain of peripheral neuropathy in the feet. This condition may be very difficult to treat
but will sometimes respond to pain medications and tricyclic antidepressant medications,
such as amitryptilline (Elavil). Unfortunately, narcotic addiction may be common in
patients with chronic painful enteric neuropathy.
Individuals with diabetes also have an increased risk of celiac sprue. In this condition, an
allergy to wheat gluten develops, leading to inflammation and thinning of the mucosa of
the small intestine. Why this association occurs is not clear. However, sprue may lead to
diarrhea, weight loss, and malabsorption of food.
This condition responds well to a gluten-free diet, but patients may have difficulty
adhering to such a diet. Diagnosis can be made with endoscopic biopsy of the small
intestine or with serological evaluation for anti-endomysial and anti-gliadin antibodies.
The Colon in Diabetes
Limited information is available regarding the effects of diabetes on the large intestine.
We do know that enteric neuropathy may affect the nerves innervating the colon, leading
to a decrease in colon motility and constipation. Anatomic abnormalities of the colon,
such as structure, tumor, or diverticulitis, should be excluded with a barium enema or
colonoscopy.
Fiber supplementation with bran or psyllium products, as well as a high-fiber diet,
increases the water content of the bowel movement and may relieve constipation. Mild
laxatives and stool softeners will often help as well. In addition, cisapride accelerates
colonic movement and may increase the frequency of bowel movements.
Diabetic Diarrhea
Patients with a longstanding history of diabetes may experience frequent diarrhea, and
this has been reported to occur in up to 22% of patients. This may be related to problems
in the small bowel or colon. Abnormally rapid transit of fluids may occur in the colon,
leading to increased stool frequency and urgency. In addition, abnormalities in the
absorption and secretion of colonic fluid may develop, leading to increased stool volume,
frequency, and water content.
Diabetic diarrhea is a syndrome of unexplained persistent diarrhea in individuals with a
longstanding history of diabetes. This may be due to autonomic neuropathy leading to
abnormal motility and secretion of fluid in the colon. There are also a multitude of
5
intestinal problems that are not unique to people with diabetes but that can cause
diarrhea. The most common is the irritable bowel syndrome.
The workup and treatment of diarrhea is similar in patients with or without diabetes. If
the basic medical evaluation of diarrhea is nondiagnostic, which it frequently is, then
treatment is tailored toward providing symptomatic care with antidiarrheal agents such as
diphenoxylate (Lomotil) or loperamide (Immodium). Fiber supplementation with bran,
Citrucel, Metamucil, or high-fiber foods may also thicken the consistency of the bowel
movement and decrease watery diarrhea. In addition, antispasmodic medicines such as
hyosymine (Levsin), dicyclomine (Bentyl), and chordiazepoxide (Librax)/clindinium
(Clindex) may decrease stool frequency.
Sometimes an empiric trial of antibiotics and/or pancreatic enzymes is warranted because
pancreatic exocrine insufficiency and bacterial overgrowth may be the etiology. More
recently, the 5HT3 receptor antagonist alosetron (Lotronex) has been used effectively for
the treatment of diarrhea-predominant irritable bowel syndrome. Tincture of opium and
paregoric have also been used to improve the quality of daily life in some cases. Finally,
in severe cases, injections of octreotide (Sandostatin), a somatostatin-like hormone, have
been shown to significantly decrease the frequency of diabetic diarrhea. Obviously, in
these severe cases, referral to a gastroenterologist is indicated.
http://www.wjgnet.com/1007-9327/5/518.asp
ISSN 1007-9327 CN 14-1219/R World J Gastroenterol 1999; December 5(6):518-521
Intestinal stasis associated bowel inflammation
Shunichiro Komatsu, Yuji Nimura, D Neil Granger
Anatomical structures that create reservoirs for stagnant intestinal contents are a characteristic
feature of common inflammatory disorders such as diverticulitis and appendicitis. Intestinal
diverticula, surgically constructed blind loops and pouches, obstructing carcinomas of the colon,
and Hirschsprung’s disease are accompanied by chronic inflammatory changes in the intestine,
and are occasionally associated with mucosal ulceration followed by massive bleeding. These
diseases are etiologically associated with disorders characterized by intestinal stasis and/or an
altered fecal stream, resulting from “cul de sac” structures (blind loop or pouch) in the intestinal
tract, bowel obstruction or impaired motility. Furthermore, some of these chronic inflammatory
conditions appear to exhibit similar pathological features, such as ischemic colitis. Although these
inflammatory changes have been described individually, often as case reports, relatively little
attention has been devoted to the overall clinical impact of these diseases and to understanding
the pathophysiology of disease initiation and progression. Studies in our laboratory and by others
have provided novel insights into the molecular and cellular basis for the intense inflammatory
responses that are associated with intestinal stasis. This review summarizes the findings of these
studies and provides a unifying theory to explain the inflammatory responses that result from
intestinal stasis.
Restorative proctocolectomy with ileal pouch anal anastomosis has become the surgical
treatment of choice for both ulcerative colitis and familial adenomatous polyposis. In spite of the
excellent functional results and improved quality of life with this procedure, major concerns
persist regarding the risks for and consequences of ileal pouchitis, a long term complication that
6
is recognized with increasing frequency. Pouchitis is a nonspecific inflammation of an ileal
reservoir that typically results in increased bowel frequency, decreased stool consistency,
diminished continence, low-grade fever, malaise, and arthralgias. Oral treatment with antibiotics,
such as metronidazole, is an effective therapy for active pouchitis［10-12］.
http://216.239.51.104/search?q=cache:UGsccrrxJacJ:medind.nic.in/maa/t03/i4/maat03i4p
306.pdf+adaptive+changes+small+bowel+stasis&hl=en
http://216.239.51.104/search?q=cache:DLCdzBr4qb8J:www.hindawi.net/access/get.aspx
%3Fjournal%3Dmi%26volume%3D7%26pii%3DS0962935198000337+adaptive+chang
es+small+bowel+stasis&hl=en
Pouchitis mini review
Appl. Environ. Microbiol., 01 1992, 111-118, Vol 58, No. 1
Copyright © 1992, American Society for Microbiology
Changes in bacterial composition and enzymatic activity in ileostomy and ileal
reservoir during intermittent occlusion: a study using dogs
JG Ruseler-van Embden, WR Schouten, LM van Lieshout and HJ Auwerda
Department of Immunology, Erasmus University, Rotterdam, The Netherlands.
Bacterial flora, activities of 10 potential mucus- and dietary polysaccharide-degrading
enzymes, blood group antigenicity of the intestinal glycoproteins, and proteolytic activity
in the output from experimentally colectomized dogs with conventional ileostomies and
dogs with valveless ileal reservoirs (pouches) were determined. The ileostomies of dogs
with conventional surgery (group II) and with pouches (group III) were occluded
intermittently during a 6-week period. The duration of occlusion was progressively
increased. Group I, five dogs with conventional ileostomies, served as a control group.
After occlusion of the ileal pouch for 7 h, total numbers of bacteria increased threefold,
glycosidase activity increased fivefold, and blood group antigenicity of the intestinal
glycoproteins, which was high in the output from the nonoccluded pouch, was no longer
detectable. Proteolytic activity was not influenced by occlusion of the pouch.
Significantly lower numbers of bacteria, only minor glycosidase activity, high blood
group antigenicities of the intestinal glycoproteins, and higher proteolytic activity were
found in ileostomy effluents from groups I and II. Histopathological examination showed
chronic inflammation and changes in crypt-villus ratio in all dogs with ileal reservoirs;
the ileal mucosa from the dogs with conventional ileostomies did not show any
abnormalities. Consequences of the flora- related enzyme activities for the ileal mucosa
are discussed.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8
959733&dopt=Citation
Neurogastroenterol Motil. 1996 Dec; 8(4):277-97.
Related Articles, Links
Biomechanics of the gastrointestinal tract.
7
Gregersen H, Kassab G.
Centre of Biomechanics and Motility, Skejby University Hospital, Denmark.
As the function of the gastrointestinal tract is to a large degree mechanical, it has
become increasingly popular to acquire distensibility data in motility research
based on various parameters. Hence it is important to know on which geometrical
and mechanical assumptions the various parameters are based. Currently,
compliance and tone derived from pressure-volume curves are by far the most
often used parameters. However, pressure-volume relations obtained in tubular
organs must be carefully interpreted as they provide no direct measure of luminal
cross-sectional area and other variables useful in plane stress and strain analysis.
Thus, erroneous conclusions concerning tissue distensibility may be deduced.
Other parameters, such as wall tension, stress and strain, give more useful
information about mechanical behaviour. Distensibility data procure significance
in fluid mechanics and in the study of tone, peristaltic reflexes, and
mechanoreceptor kinematics. Such data are needed for the determination of the
interaction between stimulus, electrical responses in neurons and the mechanical
behaviour of the gut. Furthermore, from a clinical perspective, investigation of
visco-elastic properties is important because GI diseases are associated with
growth and remodeling. For example, prestenotic dilatation, increased collagen
synthesis, dysmotility and altered distensibility are common features of
obstructive diseases. The purpose of this review is to discuss the physiological
and clinical importance of acquiring biomechanical data, distensibility parameters
and interpretation of these results and their associated errors. We will also discuss
some aspects of the relationship between morphology, growth and biomechanics.
Finally, we will outline a number of techniques to study the mechanical properties
of the GI tract.
http://www.smi.hst.aau.dk/visceralpainbiomechanics/main.html
Laboratory for Visceral Pain and Biomechanics
Studying sensation and biomechanics in visceral organs
http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowPDF&ProduktNr=223
838&Ausgabe=227607&ArtikelNr=48861&filename=48861.pdf
Sensory and Biomechanical Responses to Distension of the Normal Human Rectum
and Sigmoid Colon
Poul Petersena, Chunwen Gaoc, Petra Rössela, Peter Qvista, Lars Arendt-Nielsenc, Hans
Gregersenb, Asbjørn Mohr Drewesa,c
Departments of
a
Medical Gastroenterology and
8
b
Surgical Gastroenterology, Aalborg Hospital, and
Center for Sensory-Motor Interaction, Institute of Electronic Systems, Aalborg
University, Aalborg, Denmark
c
Digestion 2001;64:191-199 (DOI: 10.1159/000048861)
Key Words







VAS
Pain
Distensibility
Impedance planimetry
Strain
Tension
Sensibility
Abstract
Background: Visceral pain is a major clinical problem. The aim of the present study was
to compare the pain and biomechanical responses to standardized distension of the human
colon. Methods: The relation between pain intensity and pressure, cross-sectional area
(CSA) and tension-strain relations of the rectum and sigmoid colon were studied in 11
normal subjects following standardized distension using impedance planimetry. The bag
was inflated stepwise with pressures up to 6 kPa. The subjects, who were blinded for the
distension procedure, rated their pain intensity using an aggregate visual analogue score
(VAS) combining the intensity of the feeling of air, urge to defecate and pain. Results:
The distensions produced an initial rapid increase in CSA followed by a phase of slow
increase until a steady state CSA was reached after 0.5-1 min. Several phasic contractions
(observed as short-term decreases in the CSA) were recorded in the rectum from the end
of the rapid phase to the end of distension at pressures from 1 to 5 kPa. The CSA in the
rectum and sigmoid colon was 3,706 ± 426 mm2 and 2,305 ± 426 mm2 at the maximum
bag pressure of 6 kPa (F = 52.4, p < 0.001). The tension-strain relation did not differ
between the normal rectum and sigmoid colon. The VAS score for every modality (air,
defecation and pain) revealed an increase in intensity as a function of pressure. The VAS
score in the rectum and the sigmoid colon as a function of tension and strain did not show
any differences. Conclusions: The biomechanical properties in the sigmoid colon and
rectum were alike. For a given wall tension and circumferential strain the sensibility
seems equal in the rectum and the sigmoid colon. The observed difference in perception
between the two segments was related to the greater CSA in the rectum.
Copyright © 2001 S. Karger AG, Basel
Author Contacts
Hans Gregersen MD, D.Sc.
Center for Sensory-Motor Interaction, Aalborg University
9
Fredrik Bajers Vej 7D-3
DK-9220 Aalborg Ø (Denmark)
Tel. +45 96358843, Fax +45 98154008
Article Information
Received: Received: September 11, 2000
Accepted: April 30, 2001
Number of Print Pages: 9
Number of Figures: 4, Number of Tables: 0, Number of References: 32
Digestive Disease Institute, Jefferson >>> If you showed up here with a chronic
stomachache and doctors couldn’t figure out what was wrong using standard X-rays and
CT scans, they might have you swallow a tube with a camera about the size of a large
vitamin capsule at the end. That camera, which transmits images of activity in the small
intestine, would provide an inside view of the origin of the problem. Jefferson’s capsule
endoscopy program is said to be the fifth largest in the nation and is an example of this
hospital’s clinical excellence. Last year, more than 16,000 patients were seen here for a
total of 12,000 procedures. Four of the center’s outstanding doctors -- Anthony
DiMarino, Sidney Cohen, Franz Goldstein and Howard Kroop -- have been named
Physician of the Year by the Crohn’s and Colitis Foundation of America (Suite 480, 132
South 10th Street; 215-955-8900).
Motility and Functional GI Disease Center, Temple >>> For 30 years, Robert Fisher,
an expert in motility who heads this center, has been researching how food travels
through the digestive system, and treating the obstacles that get in its way. The center’s
innovative arsenal features electrogastrography (a cardiogram for charting stomach function),
electrical stimulation therapy (a gastric pacemaker for people whose stomachs don’t empty properly),
and scintigraphy (a technique to measure how food moves through the system). Temple is the only
institution doing scintigraphy outside of the Mayo Clinic. Active in research as well, the
center is currently conducting a protocol using Botox to relax different sphincters in the
GI tract (3401 North Broad Street; 215-707-3429).
http://jp.physoc.org/cgi/content/full/536/2/555
Journal of Physiology (2001), 536.2, pp. 555-568
© Copyright 2001 The Physiological Society
Loss of interstitial cells of Cajal and development of electrical dysfunction in murine
small bowel obstruction
In-Youb Chang, Nichola J. Glasgow, Ichiro Takayama, Kazuhide Horiguchi,
Kenton M. Sanders and Sean M. Ward
Department of Physiology and Cell Biology, University of Nevada School of Medicine,
Reno, NV 89557, USA
10
 Partial obstruction of the murine ileum led to changes in the gross morphology and
ultrastructure of the tunica muscularis. Populations of interstitial cells of Cajal (ICC)
decreased oral, but not aboral, to the site of obstruction. Since ICC generate and
propagate electrical slow waves in gastrointestinal muscles, we investigated whether the
loss of ICC leads to loss of function in partial bowel obstruction.
 Changes in ICC networks and electrical activity were monitored in the obstructed
murine intestine using immunohistochemistry, electron microscopy and intracellular
electrophysiological techniques.
 Two weeks following the onset of a partial obstruction, the bowel increased in
diameter and hypertrophy of the tunica muscularis was observed oral to the obstruction
site. ICC networks were disrupted oral to the obstruction, and this disruption was
accompanied by the loss of electrical slow waves and responses to enteric nerve
stimulation. These defects were not observed aboral to the obstruction.
 Ultrastructural analysis revealed no evidence of cell death in regions where the lesion
in ICC networks was developing. Cells with a morphology intermediate between smooth
muscle cells and fibroblasts were found in locations that are typically populated by ICC.
These cells may have been the redifferentiated remnants of ICC networks.
 Removal of the obstruction led to the redevelopment of ICC networks and recovery of
slow wave activity within 30 days. Neural responses were partially restored in 30 days.
 These data describe the plasticity of ICC networks in response to partial obstruction.
After obstruction the ICC phenotype was lost, but these cells regenerated when the
obstruction was removed. This model may be an important tool for evaluating the
cellular/molecular factors responsible for the regulation and maintenance of the ICC
phenotype.
http://www.wellcome.ac.uk/en/pain/microsite/science3.html#
Visceral pain
Fernando Cervero
Pain affecting our 'soft' organs and body tissues, or viscera, is extremely common and
can be agonizing. Injury and inflammation can be particularly problematic, as organs
become highly sensitive to any kind of stimulation, as in inflammatory bowel disease
and other disorders.
Visceral pain is the pain we feel when our internal organs are damaged or injured and it
is, by far, the most common form of pain.
All of us have experienced, at one time or another, pain from our internal organs, from
the mild discomfort of indigestion to the agony of a renal colic. Many forms of visceral
pain are particularly prevalent in women and are associated with their reproductive life
(period pains, labour pain or postmenopausal pelvic pain), and for both men and women,
pain of internal origin is the number one reason to consult a doctor.
Only a minority of people will suffer from neuropathic or even post-traumatic pain but all
of us will endure throughout our lives a great deal of visceral pain.
11
Until recently visceral pain was not considered to be a major problem by the very
specialists that dealt with it. Obstetricians, gynaecologists, cardiologists,
gastroenterologists and urologists were mainly concerned with the diagnosis and
treatment of the underlying disease, and their approach was to assume that if the disease
went away so would the pain. Only recently, and mainly because of popular pressure, has
pain become a subject that can be treated directly and independently of the accompanying
disease as doctors realize that this 'symptom' is often the very centre of the problem.
A strange pain
Visceral pain shows peculiarities that make it very different from pain affecting the
somatic organs (the skin, muscles, joints and bones). For instance, not all internal
organs are sensitive to pain and some can be damaged quite extensively without the
person feeling a thing. Many diseases of the liver, the lungs or the kidneys are completely
painless and the only symptoms felt by the patient are those derived from the abnormal
functioning of these organs.
On the other hand, relatively minor lesions in viscera such as the stomach, the bladder or
the ureters can produce excruciating pain. There is no close relationship between damage
and pain like that seen when the lesions affect a somatic organ.
The reasons for this strange situation lie with the innervation of the internal organs. Some
viscera are innervated by sensory neurons that signal harmful events (nociceptors) but
other internal organs lack this form of sensor, so that injuries or lesions to these organs
cannot be translated into signals that the brain would perceive as painful.
The internal organs with nociceptors are mostly the hollow viscera (the gut, the bladder,
the uterus) and it is from these organs that we get most of our visceral pain sensations.
The insides of these organs are, in effect, an extension of the external environment so
these organs are in contact with potentially harmful agents. They therefore need to be
protected by pain mechanisms.
Visceral nociceptors are very similar to those that innervate the skin or muscle. They
respond not only to intense mechanical stimuli (distension and overstretching) but also
to irritant chemicals and especially to the products of inflammation. Some visceral
nociceptors become active only after inflammation of the mucosa of the organs that they
innervate. They are particularly important in signaling pain from inflamed and sensitized
viscera.
Referred pain
Another interesting peculiarity of visceral pain is the fact that it is often felt in places
remote from the location of the affected organ. This is known as 'referred pain' and it
is often a very useful tool to diagnose diseases of internal organs.
Many people know that cardiac ischaemia produces pain in the left part of the chest and
even in the left arm and hand. This is referred cardiac pain, a sensation felt in an
otherwise normal part of the body but that it is due to a poor oxygen supply to the heart.
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Similar patterns of referred pain can be detected in diseases of the gut, the bladder or the
internal genital organs, where the pain is felt in the abdomen, the pelvic region or the
back, with the patient not being able to locate the pain very accurately.
The reason for the 'referral' of visceral pain is the lack of a dedicated sensory pathway in
the brain for information concerning the internal organs. The sensory neurons from the
viscera connect within the brain with sensory pathways that carry information from the
skin and muscles, and the brain interprets the signals that originate from internal organs
as coming from the overlying skin or muscles. This is known as 'viscero-somatic
convergence' and it is thought to be the neural basis for referred visceral pain.
However, recent studies using brain imaging have shown that the areas of the brain
activated by painful visceral stimuli are not exactly coincidental with those turned on
during somatic pain. Although viscero-somatic convergence may underlie referred pain,
there are also other factors involved in the integration of sensory information from
internal organs. [see also Mapping pain in the brain]
Sensitization
A remarkable aspect of visceral pain is the development of visceral hyperalgesia – an
increased sensitivity to visceral stimulation following an injury or inflammation of an
internal organ. We all know that a stomach upset, a simple indigestion or cystitis can not
only produce pain from the affected organs but also cause pain when the gut or the
bladder go about their normal functions, passing food or collecting urine. These simple
functions become very painful when they occur in an inflamed bladder or stomach, to the
point that the hyperalgesic sensations can be even more intense than the underlying pain.
The increased sensitivity of the viscera after inflammation has two causes:


an alteration of the sensory neurons in the viscera so that they now respond more
intensely to naturally occurring stimuli;
an enhanced sensitivity of the sensory pathways in the brain that mediate
sensations from the viscera.
Both processes are known as 'sensitization' either peripherally (in the viscera) or
centrally (in the brain) and are thought to be responsible not only for the pain produced
by the inflammatory disease but also for hyperalgesic sensations that can occur in the
absence of an identifiable cause, such as pain in conditions like irritable bowel syndrome.
This process of sensitization is currently the subject of a great deal of research, to identify
its molecular basis and to find ways to restore normal sensitivity to the distorted system.
The aim is to reduce hyperalgesic sensations caused by the regular functioning of internal
organs without interfering with the normal sensitivity of the viscera or with the digestive,
secretory or reproductive functions of the organ.
Unfortunately, we have very few specific painkillers for visceral pain, and the therapies
commonly used are extensions of those used for pain in general. Because of the
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prevalence of visceral pain, there is a great need for therapies aimed specifically at the
conditions that cause the pain. This is particularly the case for diseases characterized by
visceral hypersensitivity (such as irritable bowel syndrome), in which the therapeutic aim
should be to reduce the increased sensations felt from the bowel without damping
sensation in general or impairing the ability of the patient to live a normal life.
We may not be able to have a completely pain-free world, but we are trying to reduce the
suffering of many men and women who every day face pains that come not from outside
but from inside their own bodies.
Professor Fernando Cervero is Director of the Anesthesia Research Unit, McGill
University, Montreal, Quebec H3G 1Y6, Canada. E-mail: fernando.cervero@mcgill.ca
Further reading
Cervero F (1994) Sensory innervation of the viscera: peripheral basis of visceral pain.
Physiol. Rev. 74, 95-138.
Cervero F and Laird J M A (1999) Visceral Pain. The Lancet, 353, 2145-2148.
Gebhart G F (Ed.) (1995) Visceral Pain. Progr. Pain Res. & Manag. Vol. 5, IASP Press
(Seattle), 516pp.
Hobson A R and Aziz Q (2003) Central nervous system processing of human visceral
pain in health and disease. News Physiol Sci. 18,109-114.
Mayer E M and Gebhart G F (1994) Basic and clinical aspects of visceral hyperalgesia.
Gastroenterol. 107: 207-293
Wesselmann U (2001) Interstitial cystitis: a chronic visceral pain syndrome. Urology. 57,
(6 Suppl 1):32-39.
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Slow pain can also be the primary type of pain when it originates in internal organs: gut,
uterus, etc., except the brain, which is an organ insensitive for pain. Whereas very
localised pain on the skin, like a small cut, is painful, localised trauma to an internal
organ is not painful, e.g. when a surgeon cuts a bowel, this is not painful at all (but for the
surgeon to get to the bowel, he has to cut through skin, and that is why you need
anaesthetic).
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