Causes and Treatment Options
September 17, 2013
Eva Szigethy MD, PHD
Associate Professor of Psychiatry, University of Pittsburgh
Director, Medical Coping Clinic, Children’s Hospital of Pittsburgh
Director, Visceral Inflammation and Pain (VIP) Center
Division of Gastroenterology, Hepatology, and Nutrition
Objectives
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What are the known causes of pain in patients
with IBD?
How can different types of pain be managed
and treated?
What resources are available?
What is IBD?
Crohn’s disease (CD)
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Can affect entire
gastrointestinal tract, from
mouth to anus
Usually affects end of the small
intestine and beginning of large
intestine
Inflammation can involve entire
thickness of GI tract
Ulcerative colitis (UC)
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Affects colon only
Usually begins in rectum and
extends to colon
Inflammation is only in lining of
colon (mucosa and submucosa)
Gastrointestinal Tract
Inflammatory Bowel Disease
Characteristics
• Complicated medication
and surgical treatments
• Social isolation/ reduced
societal productivity
• Life-long since no cure
• Impaired quality of life
• High health care costs
• Increased anxiety and
depression
• Chronic abdominal pain
Benhayon & Szigethy, In: Clinical Challenges and Complications of IBD, 2012
Definition of Pain
• Unpleasant sensory and emotional experience associated
with actual or potential tissue damage.
• Universal experience, shaped by past experiences and
psychosocial factors.
• Can be acute, recurrent or chronic.
• Suffering = inherently subjective and multidimensional,
including psychological distress, social isolation, family
distress
International Association for the Study of Pain
Pain in IBD
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Abdominal pain is common in IBD
Of adults with IBD, 20% consume up to 80% of
IBD medical costs
Chronic pain and depression are key factors
effecting healthcare utilization and costs
Binion et al., 2010
Causes of Pain in IBD
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Inflammation
Strictures/adhesions/fistulas
Bacterial overgrowth-small intestine
Neurobiological
Psychological
Psychosocial
Genetics
Bielefeldt et al., Inflammatory Bowel Disease 2009; Srinath et al., Ther
Advances in Gastro 2012; Camilleri N Engl J Med 2012
Abdominal Pain
Inflammation
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Up to 50-70% of adults with IBD have abdominal pain
during flares
Inflammation releases cascade of pain-related chemicals
in brain and body as warning signals
Subtle inflammation (and consequent pain) may exist
despite remission on standard indices
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Inflammation effect on motility (serotonin)  possible pain
Bielefeldt et al., Inflamm Bowel Dis 2009; Wagtmans et al. Clin Gastro
1998; Keohane et al. Am J Gastro 2010; Schirbel et al. World J Gastro
2010; Snape et al. Am J Physiol 1991; Vermillion et al. Gastroenterol 1993
Abdominal Pain
Strictures/Adhesions/Fistulas
• Scars (strictures and adhesions) can lead to painful
obstructions
• Deep ulcers which extent from one lining of the body to
another (fistulas) can lead to painful infections
Abdominal Pain
Bacterial Overgrowth
• The metabolism of too many bacteria in the
intestine can lead to painful bloating and
cramping
Abdominal Pain
Neurological
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Inflammation affects integration of nervous system and
gut
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Gut inflammation leads to rectal hypersensitivity
Gut inflammation directly affects enteric neurons 
abdominal pain
If quiescent disease but pain:
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Microscopic gut inflammation  visceral neuronal
signaling & sensitization  visceral hypersensitivity
Anderrson et al. Dis Colon Rectum 2003; Beyak, Vanner. Neurogastroenterol Motil 2005
Geboes, Collins Neurogastroenterol Motil 1998; Lakhan, Kirchgessner. Neuroinflammation
2010; Jacobson et al. Gastroenterol 1995
Abdominal Pain
Psychological
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Depression and anxiety in adult and
pediatric IBD
Mood disorders linked to persistent pain
in quiescent IBD
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Increased worrying, limited coping ability,
somatization
Mechanisms still unclear
Szigethy et al. J Am Acad Child Adolesc Psychiatry. 2004; Fuller-Thomson,
Sulman. IBD 2006; Farrokhyar et al. IBD 2006; Srinath et al. DDW 2011
(Abstract); Graff et al IBD 2009
Psychological :Anxiety and Depression
• Anxiety and depression rates
are 25-40% in IBD
• Both anxiety and depression
associated with
– Medically unexplained
symptoms
– Worse medical course
– Increased medical costs
Helzer 1982, 1984, Addolorato 1997
Walker 1996, Maunder 2001, Mittermaier 2004,
Szigethy 2010, Moser 2006, Hauser 2011
Top Concerns of Patients with IBD
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Uncertainty
Pain/suffering
Medication effects
Surgery/Ostomy
Cancer
Lack of energy
Sleep
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Being a burden
Financial difficulties
Damaged self
Bathroom Access
Diet
Mussel, 2004; Mclafferty, 2011; Nicholas 2007; Nicholas, 2008
Abdominal Pain
Psychosocial
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Life stressors ~ coping  pain perception in IBD
Early life trauma linked to visceral
hypersensitivity
Chronic stress reactivation risk
Ross et al. JPGN 2011
Drossman. Am J Gastroenterol 2011
Engstrom J Am Academ Child Adolesc Psych 1991
Levenstein et al. Am J Gastroenterol 2000
Abdominal Pain
Genetics
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Genetic defects related to pain processing not
yet systematically studied in IBD
Genetic components may account for ~50% of
variance in pain processing
Growing potential candidate genes in IBS
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Serotonin transporter (5-HTTLPR), certain G
proteins, cholecystokinin receptor, and tumor
necrosis factor
Buscher et al. Eur J Pain. 2006; Diatchenko et al. Hum Mol Genet. 2005; Giesecke et al.
Arthritis Rheum. 2004; Hotoleanu et al. World J Gastroenterol. 2008
Akbar et al. Gut 2010
Influences on Pain Sensation
Stress
Abnormal inputs
Repetitive bowel stimulation
Acute inflammation
Infection
IBD (mild or in remission)
Neurological trauma
Operations
Invasive procedures
Zighelboim J, Dig Dis & Sci 1995; 40:819
Drossman DA et. al., Gastroenterology 2002
Interrelated Gut Factors Associated with
Visceral Sensitization
Inflammation/immune
reactivity
• Cytokines
• Lymphocytes
• Mast cells
Gut flora
• Altered microbiome
Increased Intestinal
Permeability
Drossman, 2013
Summary: Pain in IBD
• Pain involves both the gut and brain
• Acute GI pain usually results from injury to the
gut (e.g., active disease or infection)
• Chronic GI pain can result from the gut
(visceral hypersensitivity), brain (central
hypersensitivity), or both
Pain Management
Components of Pain History
(Clinical Manual of Pain Management in Psychiatry, R. Leo, APPI 2007)
Somatic
Onset/Duration
Location
Quality
Intensity
Associated
features
Aggravating
factors
Alleviating
factors
Psychological
Mood/Affect
Cognitive
Coping
Psychiatric Illness
IBD
PAIN
Social
Impact on
relationships
Capacity for
intimacy/sexuality
Activities of daily
living
Educational
Vocational
Pain Management: Medications
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IBD Medications-remission
Antispasmodics
NSAIDS and COX-2 inhibitors
Psychotropics
{Opiates}
Srinath et al.; 2012; Grover & Drossman IBD Monitor, 2009
IBD Medications: Goal Remission
• Aminosalicylates
• Antibiotics
• Corticosteroids
• Immunomodulators
• Biological response modifiers (Infliximab)
Inflammation
Antispasmodics
• Anticholinergic mechanisms helps with intestinal
spasms.
• More efficacious than placebo for functional
abdominal pain for IBS.
• Potential GI side effects: Fulminant obstruction in an
already partially obstructed gut or worsening gut
dysmotility; constipation
• Other side effects: dry mouth, urine retention, blurred
vision, tachycardia, drowsiness
Ford et. al. BMJ 2008; Ford. Evid Based Med. 2012
Nonsteroidal anti-inflammatory drugs
(NSAIDS)
• Commonly used to treat abdominal pain and
musculoskeletal symptoms associated with IBD
• Help decrease swelling and inflammation
• May increase the risk for IBD relapse and overall
increase in disease activity
• Side effect: increased bleeding due to effects on
platelet aggregation and gastric mucosa.
Kefelakes, 2009; Cryer 2005; Felder 2005; Bonner 2000
IBD—Pain Medications
• Acetaminophen: most commonly prescribed
analgesic.
• No significant anti-inflammatory, gastric or renal
effects.
• Can cause hepatotoxicity.
• Not associated with Reye’s syndrome.
Cyclooxygenase-2 (COX-2) inhibitors
• Targets enzyme involved with pain and
inflammation in the gut
• COX-2 inhibitors have not been shown to be
beneficial in terms of safety, toxicity, or even
anti-inflammatory effect.
• Stroke, heart attacks
Eckman 1997; Bonner 2001; Gornet 2002; Biancone 2003; Sandborn 2004
Opioids (Narcotics)
• Bind to CNS opioid receptors; inhibit release of pain
neurotransmitters.
• May cause respiratory depression, gastrointestinal
paresis, analgesia, euphoria, and physical dependence.
• Many side effects: constipation, nausea, vomiting,
sedation, pruritis, respiratory depression
• Associated with increased risk of mortality and death
(TREAT registry) and are not recommended in IBD
therapy
Opioid Analgesic
• Example: Tramadol
• Serotonin release and reuptake inhibition of
norepinephrine
• Side effects: Nausea, vomiting, constipation
• Effects on abdominal pain
Concerns with Opiates
• Psychological/physical
dependence
• Higher rates of
infection/mortality
• Narcotic Bowel
Syndrome (NBS)
Grunkmeier 2007; Lichenstein 2006;
There are safe ways to taper narcotics
under appropriate medical care
Pain Management: Psychotropics
• Serotonin Reuptake Inhibitors (SSRI)
• Serotonin Noradrenaline Reuptake Inhibitors
(SNRI)
• Tricyclic Antidepressants (TCA)
• Gabapentin/pregabalin
Antidepressants: SSRI, SNRI
• Unclear whether they have a
direct impact
• Or their beneficial effects are
mediated by decreasing anxiety
and depression.
• These agents have been
studied for their effect on
visceral pain within the
functional GI disorders (IBS)
moderately good results, Not
studied in IBD.
• SSRI/SNRI: Few side effects
or drug-drug interactions
Mikocka-Walus BMC Gastroenterol 2007, 2009;
Friedrich et. al. Clin. Ther. 2010 ; Rahimi 2009
Tricyclic Antidepressants (TCA)
• Effects on pain reduction and improved sleep
more rapid than antidepressant effect (3-7 days)
and at lower doses.
• Side effects include dry mouth, constipation,
blurred vision, urinary retention, confusion,
delirium.
• Autonomic side effects include orthostatic
hypotension, sweating, palpitations, tachycardia,
increased blood pressure requiring EKG
monitoring.
Gabapentin/pregabalin
• Centrally acting agents with mechanism unclear.
• They reduce neuropathic pain by attenuating the
release of many different neurotransmitters
• Has few side effects and does not require serum
monitoring.
Taylor 2007; Gale & Houghton, 2011
Placebo Effect
• In adults with IBS, range of placebo effect 2939%
– Abdominal pain response varied significantly with
increased intervention dose and frequency
• Placebo without deception (open placebo)
versus no treatment in adults with IBS
– Placebo had significantly greater impact on IBS
related symptoms but not quality of life after 21 days.
Pitz et al., Clin Gastroenterol Hepatol 2005; Ford et al., Aliment Pharm Ther 2010;
Enck et al., Eur J Gastroenterol Hepatol 2012; Kaptchuk et. al., 2010
Psychosocial Treatment Approaches
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Education
Psychotherapy
Hypnosis
Complementary
medicine
• Stress management
Education for Abdominal Pain
• The goal of education is to communicate
information about abdominal pain and its connection
with psychological triggers
• Identify factors that may exacerbate pain, such as
social reinforcement and school/work avoidance
• Family therapy targets family interactions and
relationships in order to change maladaptive
behaviors, increase tolerance of symptoms and
encourage independent coping skills
Brent M JPGN 2009; Bursch JPGN 2008; Walker Pain 2006; Chiou & Nurko, 2010
Psychotherapy:
Cognitive Behavior Therapy (CBT)
• CBT has most empirical support for treating depression
and anxiety in adults with IBD
• CBT alters behavior, perception, and thinking to change
mood and sensations
• CBT helps individuals to interrupt automatic emotional
processing which maintains negative cognitions and
rumination about pain
• CBT teaches problem-solving skills based on personal
control and the ability to adjust behavior and thoughts
accordingly = stress management
Palsson & Whitehead, 2013
One type of CBT: ACT & THINK
PRIMARY Control
• A Activities
• C Calm & Confident
• T Talents
SECONDARY Control
• T Think Positive
• H Help from a Friend
• I Identify the Silver
Lining
• N No Replaying Bad
Thoughts
• K Keep ThinkingDon’t Give Up
Hypnosis: Definition
• A state of inner absorption,
concentration and focused
attention
• An altered state of
consciousness with observable
brain changes.
• This “trance” allows access to
primitive, automatic brain
mechanisms to control
perception, memory and
somatic function.
• Utilizes the human brain’s
natural tendency to dissociate.
Driving and missed your exit?
…… Trance
Hypnosis for IBD
Adults
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Improved IBD activity and circulating cytokines
Improved quality of life
Less corticosteroid use
Decreased rectal mucosal release of substance P, histamine
Decreased rectal blood flow
Children
• Improved post-hypnosis in pain, diarrhea, inflammatory markers
• Controlled for change in medical treatment
Miller & Whorwell 2008, Mawdsley 2008, Shaol 2008
Complementary Medicine
• Exercise
• Complementary alternative medicine (CAM)
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Acupuncture
Yoga
Massage
Meditation
• Support groups
Acupuncture
• Postulated to have effects on acid secretion, GI motility
and pain sensation via release of opiates in brain and
body
• Adults with IBS-no difference to sham procedure
• Children with IBS or IBD-no support
• Greater impact than placebo in children with chronic
constipation
Schneider Gut 2006; Lembo Am J Gastroenterol 2009; Broide Dig Dis Sci 2001
Stress Management
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Biofeedback
Relaxation and breathing exercises
Meditation
Books, recordings, guided imagery, etc.
Light aerobic exercise (walking, swimming etc.)
Continuing to pursue hobbies and other activities you
enjoyed before diagnosis
• Creating a support network of friends, family, and health
care professionals
• Medication to address your emotional and mental state
Support Groups
• Crohn’s and colitis support group meetings are often intimate
gatherings where patients and their loved ones can share
their stories, seek emotional support, find answers to their
questions, and connect with a community who share their
challenges. Finding support:
– Attend support groups through your local CCFA chapter
– Power of Two Program
– CCFA’s online support group
– CCFA’s community site
Ensuring Optimal Pain Care
• Speaking with your healthcare team about your
pain
• Questions to ask
• Utilize self-management techniques
• Find and work with a pain practitioner
CCFA Resources
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Information Resource Center
Website information
Support groups–local and on-line
Power of Two–peer-to-peer mentor program
Learn more at www.ccfa.org
Summary Points
• IBD is associated with psychopathology, functional pain,
and maladaptive stress responses that increase
morbidity, suffering, and costs.
• Maximize treatment of underlying inflammation.
• Integrated, personalized behavioral interventions to
improve coping and decrease psychopathology can
impact medical outcomes.
• Pain medications as second line therapy
• Better identification of risk factors for psychological
stress can lead to prevention strategies.
Questions & Answers