PROMIS: THE GOOD, THE BAD & THE UNAPPEALING: ABDOMINAL SYMPTOMSMARGARET HEITKEMPERUNIVERSITY OF WASHINGTON

Irritable Bowel Syndrome

• Chronic abdominal pain associated with bowel pattern changes (Rome III criteria)

• Constipation• Diarrhea• Mixed

• 10-17% of US population• Most frequently diagnosed in women• Heterogeneous – range from mild to

severe

PROMIS OVERVIEW

• 2 IBS STUDIES• All incorporated PROMIS measures to look at

biological outcomes– Jarrett – Cain

Irritable Bowel Syndrome

• Questions: Are there biomarkers for symptoms in a functional disorder such as IBS?

• What do the PROMIS© measures tell us?

Irritable Bowel Syndrome

• ANSWER: It depends

PATHWAYS TO ABDOMINAL PAIN

• N = 20 IBS; N = 20 controls• Physiological measures

– Central pain processing– Proteomic/genetic– Inflammatory markers– Videocapsule

PATHWAYS TO ABDOMINAL PAIN

Purpose • Compare conditioned pain modulation (CPM)

in women with IBS to healthy control (HC) women.

• Test relationships of CPM ‘efficiency’ with IBS and psychological symptoms in women with IBS to HC women.

•

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If a patient be subject to two pains arising in different parts of the body simultaneously, the stronger blunts the other.

Hippocrates’ aphorism (460 – 377 BCE)

Diffuse Noxious Inhibitory Control (DNIC) System

Conditioned Pain Modulation (CPM)

Irritable Bowel Syndrome

Irritable Bowel Syndrome

Experimental Model CPM

Mimic naturally occurring pain inhibiting processes.

How much does the conditioning (noxious) stimulus reduce the pain response evoked by the other noxious stimulus, the test stimulus?

Test stimulus

Conditioning stimulus

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Cortex

Thalamus

Spinal cord

Caudal Medulla

Peripheral sensory nerve

pain signals 2

1

IBS patients – CPM inefficiency in 3 studies of women

PATHWAYS TO ABDOMINAL PAIN

• 20 IBS; 20 age-matched control women• Pain was rated on verbal numeric pain scale.

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MethodsRecruited – local community Screening – eligibility

- Women 18 - 45 years - IBS: Diagnosis by HCP, current

symptoms, no other pain disorders- Control group – healthy with no

pain disorders

Visit-1: Written consent, review questionnaires, brief history & physical (NP)

Visit-2: CPM testing in AM during follicular phase (menstrual cycle), 2-week diary of GI and psychological symptoms, stools, medication use

PATHWAYS TO ABDOMINAL PAIN

• 14-DAY DIARY (39 items)– 0 = NOT PRESENT– 1 = MILD– 2 = MODERATE– 3 = SEVERE

• BOWEL DISEASE QUESTIONNAIRE• SCL – 90• IBS – QUALITY OF LIFE (QOL)

PROMIS MEASURES

• Pain interference• Pain behavior

Pathways to Abdominal PainSupported by NINR, NIH

PATHWAYS TO ABDOMINAL PAIN

• Pain Behavior Short Form (PROMIS®)– Common pain behaviors (sighing, crying,), pain

severity behaviors (resting, guarding, facial expressions, asking for help) and verbal reports of pain.

• Pain Interference - Short Form (PROMIS®) – The extent to which pain hinders engagement

with social, cognitive, emotional, physical and recreational activities as well as sleep

Past 7 days

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CPM Technique

Medoc's PATHWAY Pain & Sensory Evaluation System (Israel)

• Temperatures 0ºC to 55ºC

• Heating and cooling rate up to 8ºC/second

• Thermode 30 X30 mm

• Study maximum thermode temperature 48ºC (118.4 ºF)

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• Orientation & familiarization Dominant hand 43ºC & 44ºC for 7 sec Rate pain at 6 sec Return 32ºC (90ºF) (baseline)

Rest 5 min

• Pain-6 determination 45ºC, 46ºC, 47ºC, 48ºC Confirm temp at the pain

rating of 6 • Test stimulus• Conditioning stimulus

CPM Protocol

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• Orientation• Familiarization

Rest 5 min break• Pain-6 temperature determination

Rest 5 min break

• Test stimulus Thermode set to pain-

6 temperature Rate pain at 0, 10, 20,

30 secRest 5 min

• Conditioning stimulus

CPM Technique

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CPM Technique• Pain rating of test stimulus

during conditioning stimulus Hand in 12ºC water bath for 60 sec. At 10, 20 , 30 sec - rate how painful

sensation is with a hand in the water bath

Thermode is set to Pain-6 level At 40, 50 , 60 sec rate how painful

the sensation is

• CPM Efficiency Pain ratings non-conditioned (test) minus pain ratings conditioned

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Sample Characteristics HC

(n = 20IBS

(n = 20 P-value

Demographics

Age 27.6 (5.5) 27.4 (6.6) .940

Race, % White 75% 75% 1.00

College Degree 90% 65% .127

Daily symptoms, % days moderate/severe symptoms over 2 wks

Abdominal Pain 4.0 (9.8) 28.0 (22.4) <.001

IBS symptoms 4.9 (11.4) 59.0 (24.2) <.001

Anxiety 1.2 (2.9) 17.0 (20.2) .001

Depressed 0.4 (1.9) 7.5 (13.9) .029

Stressed 6.5 (17.2) 19.3 (20.2) .008

Irritable Bowel Syndrome

PROMIS PAIN©N=20

BEHAVIOR54.1 (8.2)

INTERFERENCE56.8 (7.7)

Daily Diary (14days)

• ABDOMINAL PAIN .428* .416*

• ABD PAIN POST EATING .340 .451*

• ABD DISTENTION .205 .285

RETROSPECTIVE (3m)

• ABDOMINAL PAIN .425* .430*

• WHEN YOU HAD IT – DID IT RESTRICT YOUR ACTIVITIES

.318 .307

QUALITY OF LIFE

• PHYSICAL FX -.502* -.601*

• EMOTIONAL FX -.471* -.300

* P < .1

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Pain ratings relative to thermode temperature

Note. HC = Healthy Controls. IBS = Irritable Bowel syndrome.Linear regression used to extrapolate high temperatures for some people.

Thermode temperature N HC

(n = 20) N IBS(n = 20)

P-value

45 20 2.16 (1.48) 20 2.85 (2.22) .255

46 20 2.92 (1.75) 20 4.10 (2.13) .063

47 20 4.15 (1.74) 20 5.68 (2.05) .015

48 20 5.54 (2.14) 20 7.11 (2.32) .033

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CPM efficiency

P < .001 P < .001

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Scatterplot of CPM with IBS and Psychological Symptoms with Outlier

Correlation of CPM Efficiency with Pain Interference and Pain Behavior

• Pain Behavior (-.31, .17; -.38, .111)• Pain Interference (-.30, -.27, NS)

PATHWAYS TO ABDOMINAL PAIN

• 2nd Study• Comprehensive Self Management• N=86 women with IBS• Baseline Biological Measures

– Genetics– Proteomics– Heart rate variability– Intestinal permeability

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IBS interference Intensity vs ‘Physiological Group’ in IBS Subjects (n=86)

INTE

NSI

TY –

IBS

Inte

rfer

ence

LOW -- (HRV) -- HIGH

Abdominal Pain in Women with IBS, PMS & Dysmenorrhea

IBS Women with PMS & dysmenorrhea report greater menses-linked amplification of abdominal pain symptoms

Days pre-menses / Days post onset321-1-2-3-4-5-6-7-8-9-10

Mea

n Ab

dom

inal

Pai

n

3.0

2.5

2.0

1.5

1.0

.5

0.0

IBS+Dys+PMSIBS+PMSIBS+Dys

IBS only

Control

Conclusions

• PROMIS MEASURES– GOOD

• Compare to national populations (age, gender)• Compare to other patient populations• Add to data base with similar tools for symptoms• PROMIS PROFILE (29 items)

– BAD• One more tool

– UNAPPEALING• Use of screening?• Vetted by FDA for treatment trial outcomes?• Limited access

Thank you