The IBD Patient in Pain

Eva Szigethy MD, PhD

Associate Professor of Psychiatry, Pediatrics and Medicine

Director, Visceral Inflammation and Pain (VIP) Center

Division of Gastroenterology

szigethye@upmc.edu

Case Study

• 44 old female (Sue) with Crohn’s disease x 4 years but over past 6 months abdominal pain is worse.

• Mild increase in pain with eating. 2-3 loose stools per day. No change in pain with defecation.

• This new bout of constant pain started after C-diff infection 3 months ago- treated with antibiotic

• Current medications: Anti-TNF

• No surgeries.

Acute versus Chronic Pain• Pain: “An unpleasant sensory and emotional

experience associated with actual or potential tissue damage”

– Acute: Cause usually understood. Often result of disease, or surgery. Treatment: short-term and curative

– Chronic: Lasts > 3 months constant or 6 months intermittent. May not be linked to actual physiologic event. Psychological sequelae common Treatment: goal-oriented, non-curative

International Assoc. Study of Pain; NIH

Scales For Measuring Abdominal Pain

Single Element Measurement (Intensity)

Visual Analog Scale

Multidimensional Measurement

PROMIS pain instruments-www.nihpromis.org

Intensity, Interference, Behavior

PROMIS Pain Behavior Items

• When I was in pain I became irritable

• When I was in pain I grimaced

• When I was in pain I would lie down

• When I was in pain I moved extremely slowly

• When I was in pain I became angry

• When I was in pain I clenched my teeth

• When I was in pain I tried to stay very still

Reveki, 2009

Spectrum of Pain Diagnosis in IBD

• Acute Acute-Chronic

• Gastroenteritis or IBD flare (CD > UC)

• Recent surgery

• IBD- IBS (irritable bowel syndrome)-possible post-infectious

SUE ? Rome III criteria for

IBS

Abdominal pain at

least 3 days a month

in the last 3 months,

and also least 2 of

the following:

a. The

pain/discomfort is

relieved by

defecation

b. and/or the start of

the pain/discomfort is

associated with

altered stool

frequency

c. and/or the start of

the pain/discomfort is

associated with

altered stool form

(appearance).

Acute versus Chronic Pain

• Inflammation

• Anatomical-strictures/fistulas

• Motility

• Post-surgical recovery

• Bacterial overgrowth

• Menstrual cycle

• ?Anti-TNF-no

• Central nervous system involvement

• Psychological- anxiety, depression

• Neurobiological-visceral hyperalgesia

• Microbiome

Bielefeldt et al., Inflamm Bowel Dis 2009; Srinath et al., Ther Advances in Gastro 2012; Camilleri N Engl J Med 2012; Bharadwaj, 2015Wang, 2015; Chichlowski & Rudoloph, 2015

TREAT SOURCE

Case-continued

• CRP normal and colonoscopy negative

• IBD-IBS pain from peripheral (visceral) nerve sensitization after C-diff exposure also possible.

• Sue not going to work due to her GI symptoms and starting to limit social functioning

IBD-IBS

• 30-80% of adults with inactive IBD had irritable bowel syndrome (IBS) symptoms

• May have unrecognized inflammation

• High rates of anxiety/depression

• Early life trauma linked to visceral hypersensitivity in IBS and IBD

• Increase TRPV1 (vanilloid)

Minderhound et al., Dig Dis Sci 2004; Farrokhyar et al., Inflamm Bowel Dis 2006; Ansari et al., Eur J Gastro Hepatol 2008; Keohane, AJG 2010; Long, AJG 2010; Drossman AJG, 2011; Akbar 2012

Treatment of Pain in IBS

• Psychosocial Interventions- cognitive behavioral therapy, scripted hypnotherapy

– 8-12 sessions with practice over 3-4 months

• Low FODMAP (fermentable, oligo, di, mono saccharides and polyol) diet

Henrich Journal of psychosomatic research 2014; Palsson & Whitehead, Clinical Gastro & Hep 2013; Whorwell, 2008; Szigethy Am J Clinical Hypnosis 2015; Marsh Eur J Nutr. 2015, Ford, Am J Gastro, v 109 suppl, 2014

Pain Medications in IBS

• Antidepressants with moderate evidence

• Rifaximin for IBS-D (For IBD?? Guslandi, W J

Gastro, 2011)

• Lonaclotide and Lubiprostone for IBS-C (Contraindicated for mechanical source of pain in IBD, chronic pancreatitis, etc. and intestinal obstruction)

Ford, Am J Gastro, v 109 suppl, 2014

Case Study- next 3 months

• Teach behavioral interventions for pain management- distraction techniques and hypnosis so “brain” can be less reactive to “false alarm” pain signals.

• Behavioral sleep interventions and sleep hygeine

• “I don’t want an antidepressant- this is not mental”

Address Poor sleep

• Regularity

• Subjective satisfaction/ high quality

• Appropriate timing

• Adequate duration

• High efficiency

• Sustained alertness during waking hours

Behavioral Treatment-Insomnia

• A set of principles taught to patients over 1 month:

1. Consistency of sleep/wake times

2. Don’t go to bed unless tired

3. If not falling asleep after 20 minutes, go do something else.

4. No or brief naps.

5. Daytime activity matters

GOAL: Time in bed = Actual Sleep time

Szigethy @ Germain

Case Study-next 6 months

• Non-compliant with psychosocial interventions

• History of chronic recurrent depression

• Other pain syndromes- fibromyalgia and chronic headaches. No other medical diagnoses.

• Oxycodone and fentanyl patch x 1 month after ER visit

• Patient goes to multiple ERS to get narcotics and "fights" with staff/MDs when not given drugs.

• Currently depressed and poor sleep

Chronic Pain Suffering: Central Pain Syndromes

• Central nervous system (non-nociceptive) disturbances in pain processing with diffuse hyperalgesia

• Behavioral factors prominent

• Etiology: female, genetics, early trauma/abuse

• Repetitive exposure to stressors lead to psychological and behavioral response to chronic pain…..vicious cycles

Phillips, 2011; Leserman. 1996; 2) Drossman, 1990; 3) Longstreth, 1993; 4) McCauley, 1997

Spectrum of Pain Psychopathology in IBD

• Acute Acute-chronic Chronic Severe

• Brief pain related to gastroenteritis or IBD flare (CD > UC)

• IBD- IBS (irritable bowel syndrome)-possible post-infectious

Central chronic pain +/-

Multiple pain syndromes+/-

Childhood trauma+/-

Psychopathology+/-

Narcotic use

SUE

Chronic “central” pain does not response well to narcotics or brief

cognitive behavioral therapy

We must change the lens through which we see treatment of chronic

refractory pain.

PHYSICALInflammationObstruction

Surgery

PSYCHOLOGICALMood

CognitionsPersonality

Srinath and Szigethy 2012

Peripheral nerve damage

SufferingDisabilitySuicide

Education about Brain-Gut-Pain Connection

Central Pain Example: Borderline Personality Disorder

• Borderline personality disorder (BPD) is characterized by a pervasive and persistent pattern of instability and impulsivity.

• Instability in mood, self-image, relationships.

• Disruption on emotional, cognitive, and interpersonal domains

• Prevalence 2-10%

Borderline Personality and Pain

• High rates of chronic pain syndromes (>50%)

• Excessive use of opioids for chronic pain

• Association between borderline personality disorder and narcotic use in patients with IBD

Samsone & Samsone, 2010; Crowell 2009

Sue’s formulation

• Has many characteristics of “central” pain prone phenotype (CNS mediated pain)

– Female, history of other chronic pain syndromes, catastrophizing

– Also assess for early life trauma

• Need to assess if narcotic use has evolved into substance abuse/dependence.

Managing Challenging Behaviors in Chronic Pain:

• Clear explanation of expectations from treatment onset

• Empathic listening and repeat back what you heard

• Setting consistent limits and clear verbal and written instructions

• Validate anger but redirect toward their helplessness not their helpers

• Re-channel entitlement into realistic expectations of good care

• Arrange regular appointments not based on worsening.

• Manage your countertransference

Groves, 1978

Behavioral Interventions for Chronic Pain

• Meditation and mindfulness techniques reduce pain perception and suffering.

• Hypnosis improved acute and chronic pain across a variety of conditions.

• Moderate exercise

Astin 2002,Knittle 2010, Glombiewski 2010; Andrasik 2007; Elkin 2007; Kok 2013; Tang 2013; Palsson & Whitehead 2014; Patterson & Jensen, 2003

Treatment Plan for Sue

• Build a strong therapeutic relationship to improve motivation and educate about neurobiology of pain circuits.

• Continue to offer behavioral interventions

• Begin appropriate alternative non-opioid pain medications.

• Explore willingness to come off opiates

Non-opioid pharmacotherapy for Sue

• SSRIs (citalopram) can help anxiety and depression but rarely help pain directly.

• Add a tricyclic antidepressant at night.

• Start low and go slow. Usual dose range between 50-150 mg/day

• Analgesia starts to occur after a week and can take 3 weeks to reach max efficacy.

• Amitriptyline (3 ◦) more sedating

• Nortriptyline (2◦) less sedating

• Desipramine (2◦) least sedating

Drossman 2009; Dekel 2013; Ford, 2008; Drossman 2002; Taylor 2007; Houghton 2011; Grover 2009; Szigethy and Drossman, 2014

Antidepressant considerations

TCA SSRI SNRI

Potential benefits

PainDepressionAnxiety

DepressionAnxiety

Pain Depression

Adverse effects Sedation ConstipationHypotensionDry mouthArrhythmiaWeight gain

AgitationDiarrheaNight sweatsHeadacheSexual dysfunction

NauseaAgitationDizzinessSleepdisturbanceFatigueLiver dysfunction

Overdose Risk Moderate Minimal Minimal

Mechanistic Approach to Treatment

Descending

Inhibition

PNS

SPINAL CORD

Central SensitizationPeripheral Sensitization

NE/5HTOpioid R

TCAsSSRIsSNRIs

Opioids

Gabapentin /PGBOxycarbazepine

(OXC)Lamotrigine

Ketamine, Memantine

Dextromethorphan

Ca++

NMDA

Na++

Carbamazepine/OXCTCA

TopiramateLamotrigine

Beydoun 2002

BRAIN

FDA-Approved Treatments for Neuropathic Chronic Pain

• Carbamazepine (Trigeminal neuralgia)

• Gabapentin (PHN-herpes)

• Lidocaine patch 5% (PHN)

• Duloxetine (PDN-diabetic), PHN, Fibromyalgia)

• Pregabalin (PHN, PDN, Fibromyalgia)

• Milnacipram (Fibromyalgia)

• Capsaicin 8% (PHN)

Other Mood Stabilizers• Oxcarbazepine: Comparable analgesic effect in both

new and refractory trigeminal neuralgia to CBZ

– Dose range (900-2100mg/day)

– Much more tolerated than CBZ

• Lamotrigine (200-400mg/day): Better than placebo in trigeminal neuralgia and diabetic neuropathy but no difference for neuropathic pain

• Topiramate (400mg/day): Better than placebo in one trial but not in 3 trials.

Lindstrom 1987; Beydoun 2002; Zakrewska 1997; McCleane 1999; Eisenberg 2001; Edwards 1999

Concerns with Opiates in IBD

• No evidence of efficacy for chronic abdominal pain

• Psychological/physical dependence

• Higher rates of infection/mortality

• Narcotic Bowel Syndrome (NBS) versus Tolerance

Grunkmeier 2007; Lichenstein 2006;

Opioid Use in IBD

• Used acutely after surgical resection of the intestinal tract and to treat pain due to inflammation/obstruction in IBD.

• 5–21% of patients with IBD are on chronic narcotics in the outpatient setting.

• 20-70% inpatients with IBD use narcotics

• Risk factors: CD, substance abuse, psychiatric diagnoses, IBS, history of trauma, female gender

Edwards 2001; Cross 2005; Hanson 2009; Long 2011; Szigethy 2014

Opioid Detoxification for Sue

• Attempt outpatient taper but inpatient medical hospitalization if necessary

• 10-33% daily reduction of i.v. morphine or hydromorphine equivalent

• Continue non-opioid pain medications

• Appropriate management of bowel motility (constipation or diarrhea)

• Continue behavioral interventions

Abdominal pain scores improve but high recidivism (Phase 2 only)

60

50

30

10

0Stayed off

narcoticsn=13

Visual

Analog

Scale

(0-100)

40

20

Went back on

narcoticsn=10

Pre-detox-

ificationn=39

Post-detox-

ificationn=37

3 month follow-upDrossman DA et al. Am J Gastro 2012;107:1426

Opioid risk management if do prescribe acutely:

• State rules and regulations• Random toxicology screens and pill counts• Opioid treatment agreements • Communication with PCPs and pharmacies• Ongoing review and documentation of pain relief,

functional status• Risk assessment instruments: SOAPP-R (Screener

and Opioid Assessment for Patients w/Pain), COMM (Current opioid misuse measure), ABC (Addiction behaviors checklist)

• Take home message- have a risk management plan

Rational Approach to Chronic Pain

• Titrate one medication at a time• Start new medications at lowest possible dose• Slowly titrate (every 3-7 days) until end point of

maximal significant pain relief (>50%) or intolerable side effects.

• Continue chronic use only if significant pain relief, tolerable side effects and increased patient functioning occur.

• Polypharmacy only if partial response with first med.

• Supplement medication with psychosocial interventions.

Personalized Psychosocial Management Pathways for Pain

Active IBD

IBD MedsCoping therapy

Psychotropic medication

Inactive IBD

Cognitive behavioral

therapy

Psychotropic medication

Hypnosis

Exercise