Neuroimaging and Biomarkers in Chronic Visceral Pain

Irritable bowel syndrome (IBS) is the most common chronic visceral pain disorder ranking
among the most common of all persistent pain disorders with prevalence rates of 8-12% of the
population.3 Diagnostic criteria for IBS include persistent abdominal pain and/or discomfort
associated with changes in bowel habit. In the majority of patients, symptoms of other
co-morbid pain conditions, such as epigastric pain (functional dyspepsia), pelvic pain
(IC/PBS) and musculoskeletal pain (FM) are reported. Estimates are that >50% of the U.S.
workforce experiences some type of pain and 13% lose productive work time due to pain over a
2 week period, leading to over 60 billion dollars per year in lost productivity costs.4 There
are no generally agreed upon biomarkers for IBS, and diagnoses are exclusively based on
subjective symptom criteria. As with most of the persistent pain disorders, IBS patients and
their providers have increasingly embraced a biopsychosocial model incorporating
psychological and social factors along with physiologic factors, and this forms the basis for
integrative treatment approaches. This multimodal approach often incorporates Mind-Body
treatments, and there is a growing literature showing clinical efficacy in IBS for
interventions incorporating such Mind-Body approaches as meditation, hypnosis, yoga and
cognitive therapy.5 However, there is little understanding of the physiological mechanisms
underlying mind-body therapies, and for this reason optimization of the treatments for
specific individuals and populations is difficult.

In this project we aim to use neuroimaging based biomarkers of IBS to examine which of these
physiological measures show changes specific to a mind-body treatment with previously
documented efficacy, Mindfulness Based Stress Reduction Training or MBSR. MBSR was chosen as
a target treatment for several reasons: Recent clinical trial data suggests there is efficacy
in improving IBS symptoms with MBSR, it has demonstrated prior success with other chronic
pain conditions and there is considerable literature on meditation associated brain changes.

The primary Objective is to validate optimal biomarker candidates by assessment of treatment
responsiveness in IBS patients following Mindfulness Based Stress Reduction (MBSR). The
secondary objectives are to determine the generality of optimal biomarkers from Aim 1 and 2
and look at factors such as sex, age, co-morbid pain or mood symptoms, and/or baseline
disease severity as moderators of the performance of candidate biomarkers.

Also, exploratory analyses will be performed to assess the effect of an 8 week MBSR training
on measures of disease cognition, quality of life and mood defined by pre and post test
scores on the behavioral measures listed in the study methods.

Inclusion Criteria:

1. Patients must meet the Rome III criteria for IBS and lack red flag symptoms, such as
weight loss, bloody stool, and fever. In the setting of clinical uncertainty on the
part of the examining gastroenterologist, laboratory testing or prior medical records
may be requested.

2. Upper gastrointestinal symptoms, ie. dyspepsia or heartburn, are acceptable as long as
IBS is their most bothersome symptom complex.

3. Subject cannot have completed structured training in MBSR or other mindfulness or
meditation.

4. Subject cannot be currently practicing MBSR.

5. A minimal severity score of 75 on the IBS-SSS at screening will be required to ensure
at least mild-moderate symptoms at baseline.

6. Literate in English

7. Ambulatory without a need for assistive devices.

8. Able to participate in the sitting and mild yoga positions required for the MBSR
course.

9. Right handed due to importance of laterality in brain imaging analysis

10. Not pregnant, nursing or postpartum.

11. No metals in body, including ferrous metallic implants and tattoos

12. No history of claustrophobia.

13. Able to lay still on back for extended period of time ( about 90 minutes).

14. if unable to participate in the MRI portion of the study you may be eligible to come
to the MBSR classes at no cost if you agree to complete the classes, homework and
on-line questionnaires.

Exclusion criteria:

1. Planned major medical intervention in the next 6 months (e.g. surgery), or surgery in
the past 6 months.

2. Presence of a significant and ongoing medical problem that would interfere with
participation in the study or testing the study hypotheses (e.g. major heart disease,
neurological disorders, inflammatory bowel disease, etc).

3. Presence of a major psychiatric diagnosis such as schizophrenia, Bipolar disorder,
Post-traumatic Stress Disorder, or Obsessive Compulsive disorder. However, subjects
with a history of DSMIV diagnosis of Anxiety or Depression, in whom symptoms are not
active will be allowed but noted for post-hoc analysis.

4. use of centrally acting medications that will interfere with the neuroimaging testing
(e.g. narcotic medications). As in past studies we will allow subjects taking stable
doses of antidepressant medications (TCAs, SSRIs, SNRIs) for at least six months prior
to study to participate.

5. Body Mass Index greater than 30.

6. Current or past history of chronic pain syndrome other than IBS in the IBS group (pain
>6 months at any location).

7. History of gastrointestinal surgery other than uncomplicated appendectomy or
cholecystectomy.