Hypnosis and Irritable Bowel Syndrome

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Hypnosis and Irritable Bowel Syndrome
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IBS

• Common disorder in which bowel habits are altered
  in association with abdominal pain or discomfort

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IBS

• 12 percent among adults in the United States and
  a similar prevalence worldwide

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IBS

• By definition, no mechanical, biochemical, or
  overt inflammatory condition explains the
  symptoms.

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IBS

• Diarrhea is a symptom that often leads to medical
  consultation
• Frequent trips to the bathroom alters lifestyle
• Anxiety
• Decreased quality of life.

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IBS

• Constipation type has
• Bloating
• Discomfort
• Altered body image

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IBS

• Incidence increases during adolescence
• Peaks in the third and fourth decades
• Rare onset after 50
• Women have a (21 ratio)
• High frequency of psychosocial stress

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IBS

• Psychosocial stress appears to predict both the
  use of health care and the persistence of
  symptoms

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IBS Pathophysiology

• The cause of irritable bowel syndrome is unknown

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IBS Pathophysiology

• Associated pathophysiology includes altered
  gastrointestinal motility and increased gut
  sensitivity

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Pathophysiology

• Increased small-bowel and colonic contractions
  temporally associated with abdominal pain
• Heightened sensitivity to visceral distention,
  particularly that which is perceived as noxious
• Interplay between motor and sensory dysfunction
  appears to explain the symptoms of irritable
  bowel syndrome.

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IBS is a diagnosis of exclusion!
Irritable bowel syndrome, is classified as a
"functional" disorder. A functional disorder
refers to a disorder or disease where the primary
abnormality is an altered physiological function
rather than an identifiable structural or
biochemical cause. Thus proper testing for other
GI diseases should be undertaken before the
presumption of IBS is made.
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Manning Criteria
Distinguish IBS from organic disease are as
follows Onset of pain associated with more
frequent bowel movements Onset of pain
associated with looser bowel movements Pain
relieved by defecation Visible abdominal
bloating Subjective sensation of incomplete
evacuation more than 25 of the time Mucorrhea
more than 25 of the time
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Rome
Consensus panel created, and then updated Rome
Criteria designed to provide a standardized
diagnosis for research and clinical practice.
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The Rome II Criteria
The Rome II Criteria for the diagnosis of IBS
require that patients must have the following
continuous or recurrent symptoms for at least 3
months over 1 year Abdominal pain or
discomfort characterized by the following
Relieved by defecation Associated with a
change in stool frequency Associated with a
change in stool consistency Supporting symptoms
include the following Altered stool frequency
Altered stool form Altered stool passage
Mucorrhea Abdominal bloating or subjective
distention
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Altered GI motility?
The myoelectric activity of the normal colon has
background slow waves with superimposed spike
potentials. IBS has variations in slow-wave
frequency and a blunted, late-peaking,
postprandial response of spike potentials.
Patients who are prone to diarrhea demonstrate
this disparity to a greater degree than patients
who are prone to constipation. Hypothesize a
generalized smooth muscle hyperresponsiveness.
There have been reports of increased urinary
symptoms, including frequency, urgency, nocturia,
and hyperresponsiveness to methacholine
challenge.
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Visceral hyperalgesia?
Enhanced perception of normal motility and
visceral pain characterizes IBS. Rectosigmoid and
small bowel balloon inflation produces pain at
lower volumes in patients than in controls.
Hypersensitivity appears with rapid but not
gradual distention. Patients who are affected
describe widened dermatomal distributions of
referred pain. Sensitization of the intestinal
afferent nociceptive pathways that synapse in the
dorsal horn of the spinal cord provides a
unifying mechanism.
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Psychopathology?
Associations between psychiatric disturbances and
IBS pathogenesis are not clearly defined.
Patients with psychological disturbances relate
more frequent and debilitating illness than
control populations. Patients who seek medical
care have a higher incidence of panic disorder,
major depression, anxiety disorder, and
hypochondriasis than control populations. An
Axis I disorder coincides with the onset of GI
symptoms in as many as 77 of patients. A
higher prevalence of physical and sexual abuse
has been demonstrated in patients with IBS.
Whether psychopathology incites development of
IBS or vice versa remains unclear.
20
Central neurohormonal mechanisms?
Abnormal glutamate activation of
N-methyl-D-aspartate (NMDA) receptors, activation
of nitric oxide synthetase, activation of
neurokinin receptors, and induction of calcitonin
gene-related peptide have been observed. The
limbic system mediation of emotion and autonomic
response enhances bowel motility and reduces
gastric motility to a greater degree in patients
who are affected than in controls. Limbic system
abnormalities, as demonstrated by positron
emission tomography, have been described in
patients with IBS and in those with major
depression. The hypothalamic-pituitary axis may
be intimately involved in the origin. Motility
disturbances correspond to an increase in
hypothalamic corticotropin-releasing factor (CRF)
production in response to stress. CRF antagonists
eliminate these changes.
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microscopic inflammation?
Recently, microscopic inflammation has been
documented in some patients. This concept is
groundbreaking in that IBS had previously been
considered to have no demonstrable pathologic
alterations. Both colonic inflammation and small
bowel inflammation have been discovered in a
subset of patients with IBS as well as in
patients with inception of IBS after infectious
enteritis (postinfectious IBS). Risk factors for
developing postinfectious IBS include female
gender, longer duration of illness, the type of
pathogen involved, an absence of vomiting during
the infectious illness, and young age.
22
microscopic inflammation?
Laproscopic full-thickness jejunal biopsy samples
revealed infiltration of lymphocytes into the
myenteric plexus and intraepithelial lymphocytes
in a subset of patients. Neuronal degeneration of
the myenteric plexus was also present in some
patients. Patients with postinfectious IBS may
have increased numbers of colonic mucosal
lymphocytes and enteroendocrine cells.
Enteroendocrine cells in postinfectious IBS
appear to secrete high levels of serotonin,
increasing colonic secretion and possibly leading
to diarrhea.
23
Brain Gut connection Brain Imagery fMRI
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GUT 200554569-573 doi10.1136/gut.2004.058446
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INCREASED VISCERAL SENSITIVITY IS NOT SUFFICIENT
TO EXPLAIN PAIN REPORTS OF IBS
The emerging evidence is that central processes,
mediated by psychosocial distress, contribute to
pain perception, at least as much or more than
visceral signals. Patients with more severe IBS
are distinguished from those with milder IBS by
having greater psychological distress and
disturbances yet with no differences in visceral
sensation thresholds. Thus while chronic stress
affects reports of pain perception, it does not
appear to affect sensory thresholds. In fact, IBS
patients with a history of sexual or physical
abuse report greater pain but have higher
visceral sensation thresholds. These data
highlight the importance of central pain
processing in amplifying the perception of
visceral signals. The pain is in the central
processor (ie the ACC) and not in the gut.
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Figure 1 Structure of the cingulate cortex. The
anterior region of the mid cingulate cortex (MCC,
shown in green) is a subregion called the
anterior mid cingulate cortex of the ACC (aMCC)
it has a variety of other names including the
caudal ACC, the dorsal ACC (dACC), or cognitive
division of theACC (ACC-CD). pACC, anterior
perigenual ACC rACC, rostral ACC.
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Abnormal forebrain activity in functional bowel
disorder patients with chronic pain. C.L. Kwan,
MSc N.E. Diamant, MD G. Pope, BSc K. Mikula,
BSc D.J. Mikulis, MD and K.D. Davis,
PhD AbstractBackground Abnormal cortical pain
responses in patients with fibromyalgia and
conversion disorder raise the possibility of a
neurobiologic basis underlying so-called
functional chronic pain. Objective To use
percept-related fMRI to test the hypothesis that
patients with a painful functional bowel disorder
do not process visceral input or
sensations normally or effectively at the
cortical level. Methods Eleven healthy subjects
and nine patients with irritable bowel syndrome
(IBS) underwent fMRI during rectal distensions
that elicited either a moderate level of urge to
defecate or pain. Subjects continuously rated
their rectal stimulusevoked urge or pain
sensations during fMRI acquisition. fMRI
data were interrogated for activity related to
stimulus presence and to specific sensations.
Results In IBS, abnormal responses associated
with rectal-evoked sensations were identified in
five brain regions. In primary sensory cortex,
there were urge-related responses in the IBS but
not control group. In the medial thalamus and
hippocampus, there were painrelated responses in
the IBS but not control group. However,
pronounced urge- and pain-related activations
were present in the right anterior insula and the
right anterior cingulate cortex in the control
group but not the IBS group. Conclusions Percept-
related fMRI revealed abnormal urge- and
pain-related forebrain activity during rectal
distension in patients with irritable bowel
syndrome (IBS). As visceral stimulation evokes
pain and triggers unconscious processes related
to homeostasis and reflexes, abnormal brain
responses in IBS may reflect the sensory symptoms
of rectal pain and hypersensitivity, visceromotor
dysfunction, and abnormal interoceptive
processing. NEUROLOGY 20056512681277
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Figure 4. Major sites of activation differences
between irritable bowel syndrome (IBS) and
healthy control subjects. Brain maps indicate
urge-related activations (as indicated by the
yellow arrow) within S1 and pain-related
activations in medial thalamus and hippocampus
that appear only in the IBS group, whereas
control group images show the absence of
activation in analogous brain regions (as
indicated by the green circle). Conversely, the
control group shows prominent pain-related
activations within the dorsal anterior insula and
anterior cingulate cortex but not in the IBS
group. Right (R) and left (L) sides of the brain
are indicated in axial and coronal brain images
sagittal images were from the right hemisphere.
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Hypnosis
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Ancient History
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Asklepios(Asclepius, Roman Aesculapius)
Greek god of healing and patron deity of
physicians. Son of Apollo and the nymph Coronis.
Husband of Epione. Father of Hygieia (health) and
Panacea (all-healing). His cult originated in
Thessaly (the location of the oldest known temple
honouring him), where he was said to have been
raised by the centaur Cheiron, who taught him the
art of healing. Zeus, fearing that Asklepios
might make men immortal, killed him with a
thunderbolt. The staff used today as a symbol of
the medical profession is the winged caduceus of
Hermes minus the sinister or left handed snake.
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Asklepian dream healing temples were located on
or near springs and in an otherwise very dry
area we have several springs. One of the houses
at Aesculapia is built directly over a spring.
In some version of the myth, Asklepios' wife was
named Hygieia and was said to heal with her
hands. In the temples, the couches that the
people dreamed on were called klines. (Recline)
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Mesmer
The more recent history of hypnosis begins with
Franz Anton Mesmer who theorized that disease was
caused by imbalances of a physical force, called
animal magnetism, Mesmer believed that cures
could be achieved by redistributing this magnetic
fluid.
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Marquis de Puysegur
One of Mesmer's followers, the Marquis de
Puysegur, magnetised a shepherd on his estate. He
fell into a somnambulistic (sleeplike) state in
which he was responsive to instructions, and from
which he awoke with an amnesia for what he had
done.
42
Later in the 19th century, John Elliotson and
James Esdaile, among others, reported the
successful use of mesmeric somnambulism as an
anesthetic for surgery (although ether and
chloroform soon proved to be more reliably
effective).
43
MILTON H. ERICKSON, M.D
He is generally acknowledged to be the world's
leading practitioner of medical hypnosis. His
writings on hypnosis are the authoritative word
on techniques of inducing trance, experimental
work exploring the possibilities and limits of
the hypnotic experience, and investigations of
the nature of the relationship between hypnotist
and subject.
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What is Hypnosis?
Hypnosis is a social interaction in which one
person responds to suggestions given by another
person (the hypnotist) for imaginative
experiences involving changes in perception,
memory, and the voluntary control of action.
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Can Anyone be Hypnotized?
There are large individual differences in
response to hypnosis. Hypnosis has little to do
with the hypnotist's technique, and very much to
do with the individual's capacity, or talent, for
experiencing hypnosis. Most people are at least
moderately hypnotizable. However, while
relatively few people absolutely cannot be
hypnotized, by the same token, relatively few
people fall within the highest level of
responsiveness (so-called hypnotic virtuosos).
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How is Hypnotizability Measured?
Hypnotizability is measured by standardized
psychological tests such as the Stanford Hypnotic
Susceptibility Scale or the Harvard Group Scale
of Hypnotic Susceptibility. These instruments are
work-samples that are similar to other
performance tests. Hypnotizability, so measured,
yields a roughly normal (i.e., bell-shaped)
distribution of scores.
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Stanford Hypnotic Susceptibility Scale
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What Happens During Hypnosis?
A typical hypnosis session begins with an
induction procedure in which the person is asked
to focus his or her eyes on a fixation point,
relax, and concentrate on the voice of the
hypnotist. Although suggestions for relaxation
are generally part of the hypnotic induction
procedure, people can respond positively to
hypnotic suggestions while engaged in vigorous
physical activity. The hypnotist then gives
suggestions for further relaxation, or a
deepening, with focused attention, and often eye
closure. After the persons eyes are closed,
further suggestions for various imaginative
experiences are given. Posthypnotic suggestions
may also be given for responses to occur after
hypnosis has been terminated. The patient is
then re-alerted.
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The Ability to be Hypnotized Varies with Age
Cross-sectional studies of different age groups
show a developmental curve, with very young
children relatively unresponsive to hypnosis.
Hypnotizability reaches a peak at about the
onset of adolescence but then scores generally
drop off among middle-aged and elderly
individuals. Longitudinal studies indicate that
hypnotizability assessed in college students
remains about as stable as IQ over a period of 25
years.
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Self Hypnosis
All hypnosis is self-hypnosis. The hypnotist
does not hypnotize the individual. The hypnotist
serves as a sort of coach or tutor. While it
takes very little skill to be a hypnotist. It
takes considerable training and expertise to use
hypnosis wisely and appropriately in clinical
practice. Beyond rapport development, the most
important factor determining hypnotic response is
the hypnotizability of the individual.
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The Ability to be Hypnotized Relates to
Personality
Hypnotizability is not substantially related to
other individual differences in ability or
personality, such as intelligence or adjustment.
It does not appear to be related to individual
differences in conformity, persuasibility, or
response to other forms of social influence.
Hypnotizability is related to an individuals
disposition to have hypnosis-like experiences
outside of formal hypnotic settings. Josephine
Hilgard showed that hypnotizable individuals tend
to display a high level of imaginative
involvement in domains such as reading and drama.
Absorption is the most reliable personality
correlate of hypnotizability. By contrast,
vividness of mental imagery is essentially
unrelated to hypnosis.
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What Happens to the Brain during Hypnosis?
Although hypnosis is commonly induced with
suggestions for relaxation and even sleep, brain
activity in hypnosis more closely resembles that
of a person who is awake. The discovery of
hemispheric specialization, with the left
hemisphere geared to analytic and the right
hemisphere to non-analytic tasks, led to the
speculation that hypnotic response is somehow
influenced by right-hemisphere activity. Studies
employing both behavioral and electrophysiological
mechanisms have been interpreted as indicating
increased activation of the right hemisphere of
the brain among highly hypnotizable individuals,
but positive results have proved difficult to
replicate and interpretation of these findings
remains controversial.
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Derbyshire, Stuart W G. Whalley, Matthew G.
Stenger, V Andrew. Oakley, David A.
Department of Anesthesiology, University of
Pittsburgh Medical Center, Pittsburgh, PA 15213,
USA. derbyshiresw_at_anes.upmc.edu Cerebral
activation during hypnotically induced and
imagined pain. Neuroimage. 23(1)392-401, 2004
Sep.
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Derbyshire, Stuart W G. Whalley, Matthew G.
Stenger, V Andrew. Oakley, David A.
.In contrast with imagined pain, functional
magnetic resonance imaging (fMRI) revealed
significant changes during this hypnotically
induced (HI) pain experience within the thalamus
and anterior cingulate (ACC), insula, prefrontal,
and parietal cortices. These findings compare
well with the activation patterns during pain
from nociceptive sources and provide the first
direct experimental evidence in humans linking
specific neural activity with the immediate
generation of a pain experience.
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We can speculate on the basis of our findings of
increased BOLD signals in the left hemispheric
ACC and the basal ganglia and less activation of
the classic pain network under hypnosis that the
left ACC and basal ganglia might play a role in
increasing inhibitory signals, which in turn may
lead to a loss of signal from painful thermal
stimuli in the more proximal sensory cortex.
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Raz
Hypnotic suggestion reduces conflict in the human
brain Amir Raz, Jin Fan, and Michael I.
Posner Sackler Institute for Developmental
Psychobiology, Weill Medical College of Cornell
University, New York, NY 10021 Contributed by
Michael I. Posner, April 13, 2005
99789983 PNAS July 12, 2005 vol. 102 no. 28
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Raz
Many studies have suggested that conflict
monitoring involves the anterior cingulate cortex
(ACC). We previously showed that a specific
hypnotic suggestion reduces involuntary conflict
and alters information processing in highly
hypnotizable individuals. Hypothesizing that such
conflict reduction would be associated with
decreased ACC activation, we combined
neuroimaging methods to provide high temporal and
spatial resolution and studied highly and
less-hypnotizable participants both with and
without a suggestion to interpret visual words as
nonsense strings. Functional MRI data revealed
that under posthypnotic suggestion, both ACC and
visual areas presented reduced activity in highly
hypnotizable persons compared with either
no-suggestion or less-hypnotizable controls.
Scalp electrode recordings in highly hypnotizable
subjects also showed reductions in posterior
activation under suggestion, indicating visual
system alterations. Our findings illuminate how
suggestion affects cognitive control by
modulating activity in specific brain areas,
including early visual modules, and provide a
more scientific account relating the neural
effects of suggestion to placebo.
Fig. 1. Stroop conflict (incongruent minus
congruent) fMRI data. (A) Interaction between
group (highly hypnotizable, less-hypnotizable)
and suggestion (absent, present). Compared with
the less-hypnotizable controls, conflict
reduction (i.e., activation decrease) was
significant in the highly hypnotizable
individuals (Tables 13). (B and C)
Interpretation of highly suggestible fMRI absent
posthypnotic suggestion (B) and under
posthypnotic suggestion (C) to construe the
stimuli as nonsense strings proposes that no
difference was detected between incongruent and
congruent trials. Whereas prefrontal activations
(e.g., crosshair at the ACC) probably correlated
with cognitive control, posterior activations
might relate to early occipital modulation or
aspects of visual word recognition.
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Hypnosis Research In IBS
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Does it work?
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Worwell
Whorwell PJ Prior A Faragher EB. Controlled
trial of hypnotherapy in the treatment of severe
refractory irritable-bowel syndrome. The Lancet
1984, 2 1232-4.
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Whorwell

• placebo-controlled
• Thirty patients with severe symptoms unresponsive
  to other treatment were randomly chosen to
  receive 7 sessions of hypnotherapy (15 patients)
  or 7 sessions of psychotherapy plus placebo pills
  (15 patients).
• The psychotherapy group showed a small but
  significant improvement in abdominal pain and
  distension, and in general well-being but not
  bowel activity pattern.
• The hypnotherapy patients showed a dramatic
  improvement in all central symptom. The
  hypnotherapy group showed no relapses during the
  3-month follow-up period.

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Whorwell
Whorwell PJ Prior A Colgan SM. Hypnotherapy in
severe irritable bowel syndrome further
experience. Gut, 1987 Apr, 284, 423-5.
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Whorwell
Further experience with 35 patients added to the
15 treated with hypnotherapy in the 1984 Lancet
study. For the whole 50 patient group, success
rate was 95 for classic IBS cases, but
substantially less for IBS patients with atypical
symptom picture or significant psychological
problems. The report also observed that
patients over age 50 seemed to have lower success
rate from this treatment.
69
Harvey
Harvey RF Hinton RA Gunary RM Barry RE.
Individual and group hypnotherapy in treatment of
refractory irritable bowel syndrome. Lancet,
1989 Feb, 18635, 424-5.
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Harvey
This study employed a shorter hypnosis treatment
course than other studies for IBS. Twenty out of
33 patients with refractory irritable bowel
syndrome treated with four sessions of
hypnotherapy in this study improved. Success
rate was lower demonstrating that a larger number
of sessions is necessary for optimal
benefit. Groups of up to 8 patients seems as
effective as individual therapy.
71
Prior
Prior A, Colgan SM, Whorwell PJ. Changes in
rectal sensitivity after hypnotherapy in patients
with irritable bowel syndrome. Gut 199031896.
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Prior
IBS patients to be less sensitive to pain and
other sensations induced via balloon inflation in
their gut while they were under hypnosis.
Sensitivity to some balloon-induced gut
sensations (although not pain sensitivity) was
reduced following a course of hypnosis treatment.
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Houghton
Houghton LA Heyman DJ Whorwell PJ.
Symptomatology, quality of life and economic
features of irritable bowel syndrome--the effect
of hypnotherapy. Aliment Pharmacol Ther, 1996
Feb, 101, 91-5.
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Houghton
Compared 25 severe IBS patients treated with
hypnosis to 25 patients with similar symptom
severity treated with other methods significant
improvement in all central IBS symptoms, fewer
visits to doctors, lost less time from work than
the control group and rated their quality of life
more improved. Those patients who had been
unable to work prior to treatment resumed
employment in the hypnotherapy group but not in
the control group. The study quantifies the
substantial economic benefits and improvement in
health-related quality of life which result from
hypnotherapy for IBS on top of clinical symptom
improvement.
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Koutsomanis
Koutsomanis D. Hypnoanalgesia in the irritable
bowel syndrome. Gastroenterology 1997, 112,
A764.
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Koutsomanis
This French study with a 6-month and 12-month
follow-up. Less analgesic medication use
required and less abdominal pain experienced by a
group of 12 IBS patients after a course of 6-8
analgesia-oriented hypnosis sessions.
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Houghton
Houghton LA, Larder S, Lee R, Gonsalcorale WM,
Whelan V, Randles J, Cooper P, Cruikshanks P,
Miller V, Whorwell PJ. Gut focused hypnotherapy
normalises rectal hypersensitivity in patients
with irritable bowel syndrome (IBS).
Gastroenterology 1999 116 A1009.
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Houghton
Twenty-three patients each received 12 sessions
of hypnotherapy. Significant improvement was
seen in the severity and frequency of abdominal
pain, bloating and satisfaction with bowel habit.
A subset of the treated patients who were found
to be unusually pain-sensitive in their
intestines prior to treatment (as evidenced by
balloon inflation tests) showed normalization of
pain sensitivity, and this change correlated with
their pain improvement following treatment.
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Does this work outside of Manchester England?
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Vidakovic
Vidakovic Vukic M. Hypnotherapy in the treatment
of irritable bowel syndrome methods and results
in Amsterdam. Scand J Gastroenterol Suppl, 1999,
23049-51. Reports results of treatment of
27patients of gut-directed hypnotherapy tailored
to each individual patient. All of the 24 who
completed treatment were found to be improved.
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Galovski
Galovski TE Blanchard EB. Appl Psychophysiol
Biofeedback, 1998 Dec, 234, 219-32. Eleven
patients completed hypnotherapy, with improvement
reported for all central IBS symptoms, as well as
improvement in anxiety. Six of the patients were
a waiting-control group for comparison, and did
not show such improvement while waiting for
treatment.
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Does this therapy hold up over time?
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Gonsalkorale
Gonsalkorale WM, Houghton LA, Whorwell PJ.
Hypnotherapy in irritable bowel syndrome a
large-scale audit of a clinical service with
examination of factors influencing
responsiveness. Am J Gastroenterol 2002
Apr97(4)954-61.
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Gonsalkorale
Largest case series of IBS patients treated to
date. 250 unselected IBS patients treated in
Manchester England 12 sessions of hypnotherapy
over a 3-month period plus home practice between
sessions. Marked improvement was seen in all IBS
symptoms IBS severity was reduced by more than
half on the average after treatment All
subgroups of patients appeared to do equally well
except males with diarrhea, who improved far less
than other patients.
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What is the mechanism of action?
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Olafur Palsson Ph.D.
http//www.ibshypnosis.com/
http//www.med.unc.edu/medicine/fgidc/
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Palsson
Palsson OS, Turner MJ, Johnson DA, Burnett CK,
Whitehead WE. Hypnosis treatment for severe
irritable bowel syndrome investigation of
mechanism and effects on symptoms. Dig Dis Sci
2002 Nov47(11)2605-14.
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Palsson
Possible physiological and psychological
mechanisms of hypnosis treatment for IBS were
investigated in two studies. Patients with
severe IBS received seven biweekly hypnosis
sessions and used hypnosis audiotapes at home.
Rectal pain thresholds and smooth muscle tone
were measured with a barostat before and after
treatment in 18 patients (study I), and treatment
changes in heart rate, blood pressure, skin
conductance, finger temperature, and forehead
electromyographic activity were assessed in 24
patients (study II).
91
Palsson
All central IBS symptoms improved substantially
from treatment in both studies. Rectal pain
thresholds, rectal smooth muscle tone, and
autonomic functioning (except sweat gland
reactivity) were unaffected by hypnosis
treatment. However, somatization and
psychological distress showed large decreases.
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Palsson
Hypnosis improves IBS symptoms through reductions
in psychological distress and somatization.
Improvements were unrelated to changes in the
physiological parameters measured. 17 of 18
patients in study 1 and 21 of 24 patients in
study 2 were judged substantially improved
Improvement was well-maintained at 10-12 month
follow up in study 2.
93
Lea
Lea R, Houghton LA, Calvert EL, Larder S,
Gonsalkorale WM, Whelan V, Randles J, Cooper P,
Cruickshanks P, Miller V, Whorwell
PJ. Gut-focused hypnotherapy normalizes
disordered rectal sensitivity in patients with
irritable bowel syndrome. Alimentary
Pharmacology Therapeutics 2003 Mar
117(5)635-42.
94
Lea
Twenty-three IBS patients were tested before and
after 12 weeks of hypnotherapy. Following the
course of hypnotherapy, the mean pain sensory
threshold increased in the hypersensitive
subgroup and tended to decrease in the
hyposensitive group, although the reduction in
gut pain sensitivity was associated with a
reduction in abdominal pain. These results
suggest that hypnotherapy may work at least
partly by normalizing bowel perception in those
patients who have abnormal gut sensitivity, while
leaving normal sensation unchanged.
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Is it all in the head?
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Gonsalkorale
Gonsalkorale WM, Toner BB, Whorwell PJ.
Cognitive change in patients undergoing
hypnotherapy for irritable bowel syndrome. J
Psychosom Res. 2004 Mar56(3)271-8.
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Gonsalkorale
Cognitive changes were evaluated in 78 IBS
patients who completed a 12-session hypnosis
treatment course, using the Cognitive Scale for
Functional Bowel Disorders. Hypnotherapy
resulted in improvement of symptoms, quality of
life, anxiety and depression. Unhelpful
IBS-related cognitions improved significantly,
with reduction in the total cognitive score and
all component themes related to bowel function.
Overall symptom reduction correlated with an
improvement on the cognitive scale.
98
Since there are so few trained medical
hypnotists, does taped hypnosis work?
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Palsson
Palsson OS, Turner MJ, Whitehead WE. Hypnosis
home treatment for irritable bowel syndrome a
pilot study. Int J Clin Exp Hypn. 2006
Jan54(1)85-99.
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Palsson
A 3-month home-treatment version of a scripted
hypnosis protocol previously shown to improve all
central IBS symptoms was completed by 19 IBS
patients. Outcomes were compared to those of 57
matched IBS patients from a separate study
receiving only standard medical care. Ten of the
hypnosis subjects (53) responded to treatment by
3-month follow-up (response defined as more than
50 reduction in IBS severity) vs. 15 (26) of
controls. Hypnosis subjects improved more in
quality of life scores compared to controls.
Anxiety predicted poor treatment response.
Hypnosis responders remained improved at 6-month
follow-up. Although response rate was lower than
previously observed in therapist-delivered
treatment, hypnosis home treatment may double the
proportion of IBS patients improving
significantly across 6 months.
101
Scripts or no scripts?
102
Barabasz
Barabasz A, Barabasz M. Effects of tailored and
manualized hypnotic inductions for complicated
irritable bowel syndrome patients. Int J Clin
Exp Hypn. 2006 Jan54(1)100-12.
103
Barabasz
Eight IBS patients previously unresponsive to any
treatment were assigned randomly to either the
individualized tailored induction or standardized
Palsson script. The tailored group continued to
improve and showed better results than the
standardized group at 10-month follow-up, and the
post-treatment emotional distress had decreased
significantly.
104
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105
THE CNS IS WIRED TO MODULATE VISCERAL
AFFERENT PAINFUL SIGNALS AND RESPONSES TO STRESS.
The gate control pain system allows for
bidirectional signals between the gut and brain.
It begins with visceral signals ascending to the
CNS via the dorsal horn of the spinal cord,
through the thalamus, and then laterally to the
somatosensory cortex and medially to the insula,
medial thalamus, amygdala, and cingulate cortex.
Amplification of these signals can occur at the
level of the mucosa via sensitisation from
inflammation or injury, at the dorsal horn
(central sensitisation), or higher at midbrain
structures. In addition, corticofugal pathways
from the emotional motor system via the
periaqueductal gray and nucleus raphe magnus
descend to the dorsal horn where they can amplify
or suppress afferent signals from the gut.
Furthermore, these descending pain systems in
addition to neuroendocrine (for example,
hypothalamic-pituitary-adrenal axis), cognitive-
attentional, and autonomic control loci are
closely integrated, and mediate and affect stress
responses. This occurs to a greater degree in
patients with IBS who show increased motor,
sensory, and autonomic reactivity via these
central modulatory systems.
106
Mohr, C. Binkofski, F. Erdmann, C. Buchel, C.
Helmchen, C.Neuroimage Nord (NIN), Department of
Neurology, University of Lubeck, Ratzeburger
Allee 160, 23538 Lubeck, Germany. The anterior
cingulate cortex contains distinct areas
dissociating external from self-administered
painful stimulation a parametric fMRI
study. Pain. 114(3)347-57, 2005 Apr.
107
The anterior cingulate cortex (ACC) has a pivotal
role in human pain processing by integrating
sensory, executive, attentional, emotional, and
motivational components of pain. Cognitive
modulation of pain-related ACC activation has
been shown by hypnosis, illusion and
anticipation. The expectation of a potentially
noxious stimulus may not only differ as to when
but also how the stimulus is applied. These
combined properties led to our hypothesis that
ACC is capable of distinguishing external from
self-administered noxious tactile stimulation.
Thermal contact stimuli with noxious and
non-noxious temperatures were self-administered
or externally applied at the resting right hand
in a randomized order. Two additional conditions
without any stimulus-eliciting movements served
as control conditions to account for the
certainty and uncertainty of the impending
stimulus. Calculating the differences in the
activation pattern between self-administered and
externally generated stimuli revealed three
distinct areas of activation that graded with
perceived stimulus intensity (i) in the
posterior ACC with a linear increase during
external but hardly any modulation for the
self-administered stimulation, (ii) in the
midcingulate cortex with activation patterns
independent of the mode of application and (iii)
in the perigenual ACC with increasing activation
during self-administered but decreasing
activation during externally applied stimulation.
These data support the functional segregation of
the human ACC the posterior ACC may be involved
in the prediction of the sensory consequences of
pain-related action, the midcingulate cortex in
pain intensity coding and the perigenual ACC is
related to the onset uncertainty of the impending
stimuli.
108
pain intensity coding
prediction of the sensory consequences of
pain-related action
the onset uncertainty of the impending stimuli
109
Abnormal forebrain activity in functional bowel
disorder patients with chronic pain. C.L. Kwan,
MSc N.E. Diamant, MD G. Pope, BSc K. Mikula,
BSc D.J. Mikulis, MD and K.D. Davis,
PhD AbstractBackground Abnormal cortical pain
responses in patients with fibromyalgia and
conversion disorder raise the possibility of a
neurobiologic basis underlying so-called
functional chronic pain. Objective To use
percept-related fMRI to test the hypothesis that
patients with a painful functional bowel disorder
do not process visceral input or
sensations normally or effectively at the
cortical level. Methods Eleven healthy subjects
and nine patients with irritable bowel syndrome
(IBS) underwent fMRI during rectal distensions
that elicited either a moderate level of urge to
defecate or pain. Subjects continuously rated
their rectal stimulusevoked urge or pain
sensations during fMRI acquisition. fMRI
data were interrogated for activity related to
stimulus presence and to specific sensations.
Results In IBS, abnormal responses associated
with rectal-evoked sensations were identified in
five brain regions. In primary sensory cortex,
there were urge-related responses in the IBS but
not control group. In the medial thalamus and
hippocampus, there were painrelated responses in
the IBS but not control group. However,
pronounced urge- and pain-related activations
were present in the right anterior insula and the
right anterior cingulate cortex in the control
group but not the IBS group. Conclusions Percept-
related fMRI revealed abnormal urge- and
pain-related forebrain activity during rectal
distension in patients with irritable bowel
syndrome (IBS). As visceral stimulation evokes
pain and triggers unconscious processes related
to homeostasis and reflexes, abnormal brain
responses in IBS may reflect the sensory symptoms
of rectal pain and hypersensitivity, visceromotor
dysfunction, and abnormal interoceptive
processing. NEUROLOGY 20056512681277
110
Figure 2. Brain maps showing the spatial extent
of stimulus-related (A) and urge-related (B)
activations in both control and irritable bowel
syndrome (IBS) groups during low-pressure rectal
distensions that elicited a moderate level of
urge. Control activations are displayed in green,
IBS activations are displayed in orange, and
regions of overlap are displayed in yellow. Maps
show 18 contiguous 4-mm-thick axial slices from
58 mm above to 10 mm below the anteriorposterior
commissure line and 4 contiguous 5-mm-thick
sagittal slices centered at midline. All
activations shown at a corrected map-wise
threshold of p 0.05 (also see Methods).
111
Figure 3. Brain maps showing the spatial extent
of stimulus-related (A) and pain-related (B)
activations in both control and irritable bowel
syndrome (IBS) groups during high-pressure rectal
distensions that elicited a moderate level of
pain. Control activations are displayed in green,
IBS activations are displayed in orange, and
regions of overlap are displayed in yellow. Maps
show 18 contiguous 4-mm-thick axial slices from
58 mm above to 10 mm below the anteriorposterior
commissure line and 4 contiguous 5-mm-thick
sagittal slices centered at midline. All
activations shown at a corrected map-wise
threshold of p 0.05
112
IBS
Control
The control group shows prominent pain related
activations within the dorsal anterior insula and
anterior cingulate cortex but not in the IBS
group.
113
Raz
Many studies have suggested that conflict
monitoring involves the anterior cingulate cortex
(ACC). We previously showed that a specific
hypnotic suggestion reduces involuntary conflict
and alters information processing in highly
hypnotizable individuals. Hypothesizing that such
conflict reduction would be associated with
decreased ACC activation, we combined
neuroimaging methods to provide high temporal and
spatial resolution and studied highly and
less-hypnotizable participants both with and
without a suggestion to interpret visual words as
nonsense strings. Functional MRI data revealed
that under posthypnotic suggestion, both ACC and
visual areas presented reduced activity in highly
hypnotizable persons compared with either
no-suggestion or less-hypnotizable controls.
Scalp electrode recordings in highly hypnotizable
subjects also showed reductions in posterior
activation under suggestion, indicating visual
system alterations. Our findings illuminate how
suggestion affects cognitive control by
modulating activity in specific brain areas,
including early visual modules, and provide a
more scientific account relating the neural
effects of suggestion to placebo.
Fig. 1. Stroop conflict (incongruent minus
congruent) fMRI data. (A) Interaction between
group (highly hypnotizable, less-hypnotizable)
and suggestion (absent, present). Compared with
the less-hypnotizable controls, conflict
reduction (i.e., activation decrease) was
significant in the highly hypnotizable
individuals (Tables 13). (B and C)
Interpretation of highly suggestible fMRI absent
posthypnotic suggestion (B) and under
posthypnotic suggestion (C) to construe the
stimuli as nonsense strings proposes that no
difference was detected between incongruent and
congruent trials. Whereas prefrontal activations
(e.g., crosshair at the ACC) probably correlated
with cognitive control, posterior activations
might relate to early occipital modulation or
aspects of visual word recognition.
114
pain intensity coding
Hypnosis works here
prediction of the sensory consequences of
pain-related action
the onset uncertainty of the impending stimuli
115
Conclusions Acupuncture in IBS is primarily a
placebo response.
116
American College of Gastroenterology Functional
Gastrointestinal Disorders Task Force
1992
Behavioral therapy is more effective than placebo
at relieving individual IBS symptoms (Grade B
Recommendation)
Level I Evidence Randomized controlled trials
with p values 0.05, adequate sample sizes, and
appropriate methodology Level II Evidence
Randomized controlled trials with p values 0.05
and/or inadequate sample sizes and/or inappropriat
e methodology Level III Evidence Nonrandomized
trials with contemporaneous controls Level IV
Evidence Nonrandomized trials with historical
controls Level V Evidence Case studies Grade A
Recommendations Recommendations supported by
Level I evidence Grade B Recommendations
Recommendations supported by Level II
evidence Grade C Recommendations Recommendations
supported by Level IIIIV evidence
117
Evidence Based Grade B

• The American College of gastroenterologist rated
  behavioral therapy as class B but did not break
  out hypnosis by itself.
• This equates to Level II Evidence Randomized
  controlled trials with p values 0.05 and/or
  inadequate sample sizes and/or inappropriate
  methodology

Hypnosis and other behavior modalities were
lumped together.
118
Review article Irritable Bowel Syndrome Howard
R. Mertz, M.D. N Engl J Med 20033492136-46.
119
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120
In summary, tegaserod is moderately effective for
symptoms of constipation-predominant IBS in
women, probably due to prokinetic effects. It
appears to be very safe and has infrequent side
effects.
After introduction of alosetron, ischemic colitis
was diagnosed in approximately 1 of 700 patients
treated. The drug was withdrawn by the
manufacturer. In part due to input from patient
advocacy groups, the FDA authorized
reintroduction of alosetron in June 2002 under
specific guidelines, including a consent form
signed by the patient and a certificate signed by
the prescribing physician.45 The drug became
available again in late 2002. Given its side
effects, alosetron should be limited to women
with nonconstipated IBS who have symptoms severe
enough to risk ischemic colitis and who have not
responded other therapy.
Psychotherapeutics and Serotonin Agonists and
Antagonists by Howard Mertz, MD (J Clin
Gastroenterol 200539S247-S250)
121
Testimony of Sidney M. Wolfe M.D. Director,
Public Citizens Health Research Group Before
FDA Gastrointestinal Drugs and Drug Safety
Advisory Committee Hearing Concerning
Alosetron April 23, 2002 Benefits of Alosetron
Serious Problem with Irritable Bowel Syndrome
Studies Because of Very High Placebo Response
Rate In a review of 27 randomized
placebo-controlled studies testing various
treatments for irritable bowel syndrome (see
below), the median placebo response rate was 47
(measured as improved) with rates as high as
84 and 11 studies had placebo response rates of
60 or greater. The study concluded that this
placebo response rate was approximately three
times the size of the difference between placebo
and drug response (median 16).  
122
That this problem of a large placebo response is
applicable to alosetron can be seen in a
reanalysis by Public Citizens Health Research
Group of Glaxo data that was published in the
Lancet, shown below. The mean pain and discomfort
scores over a three-month period were quite
similar in the alosetron and placebo groups even
though there was a statistically significant
difference between the groups as analyzed by
Glaxo and the FDA.
123
From the GSK Package insert for Lotronex
(alosetron) The efficacy of LOTRONEX Of the
633 women on LOTRONEX and 640 on placebo, about
two thirds had diarrhea-predominant IBS. Compared
with placebo, 10 to 19 more women with
diarrhea-predominant IBS who received LOTRONEX
had adequate relief of IBS abdominal pain and
discomfort during each month of the study.
Hypnosis
124
Conclusions

• Often a specific therapy pre-dates the basic
  science, basic IBS hypnosis research is catching
  up to the clinical findings
• The use of hypnosis to treat IBS has been
  established but not promoted
• Evidence based B grade from 1992 did not separate
  hypnosis from other behavior methods and the
  current research suggests a B grade should be an
  A
• The symptom reduction is robust at 53-81
  improvement and exceeds any current drug
• Lotrenox studies are in question and ischemic
  colitis is a serious side-effect
• We need to do a medication vs hypnosis study as
  well as placebo
• This therapy is long lasting
• Hypnosis seems to work through the reduction in
  the perception of pain and probably has something
  to do the ACC
• We need to study fMRI for IBS hypnosis before and
  after with a control group
• The effectiveness of hypnosis is improved with an
  individualized personal approach rather than
  tapes so more therapists will need to be trained
• Hypnosis is safe
• Hypnosis is not a Svengali movie and the patients
  do not cluck like chickens!

125
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