PROMIS: THE GOOD, THE BAD & THE
UNAPPEALING: ABDOMINAL SYMPTOMS
MARGARET HEITKEMPER
UNIVERSITY 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.
•
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
8
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
Cortex
IBS patients – CPM
Thalamus
inefficiency in 3 studies
of women
Caudal Medulla
pain signals 2
Spinal cord
1
Peripheral sensory nerve
10
PATHWAYS TO ABDOMINAL PAIN
• 20 IBS; 20 age-matched control women
• Pain was rated on verbal numeric pain scale.
Methods
Recruited – 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
12
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 Pain
Supported 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
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)
16
CPM Protocol
• 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
17
CPM
Technique
• Orientation
• Familiarization
Rest 5 min break
• Pain-6 temperature determination
Rest 5 min break
• Test stimulus
 Thermode set to pain6 temperature
 Rate pain at 0, 10, 20,
30 sec
Rest 5 min
• Conditioning stimulus
18
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
19
Sample Characteristics
HC
(n = 20
IBS
(n = 20
27.6 (5.5)
27.4 (6.6)
Race, % White
75%
75%
College Degree
90%
65%
P-value
Demographics
Age
.940
1.00
.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
20
PROMIS PAIN©
BEHAVIOR
N=20Bowel Syndrome
54.1 (8.2)
Irritable
INTERFERENCE
56.8 (7.7)
Daily Diary (14days)
• ABDOMINAL PAIN
.428*
.416*
• ABD PAIN POST EATING
.340
.451*
• ABD DISTENTION
.205
.285
.425*
.430*
RETROSPECTIVE (3m)
• ABDOMINAL PAIN
• WHEN YOU HAD IT – DID IT .318
RESTRICT YOUR ACTIVITIES
.307
QUALITY OF LIFE
• PHYSICAL FX
-.502*
-.601*
• EMOTIONAL FX
-.471*
-.300
* P < .1
Pain ratings relative to thermode
temperature
Thermode
temperature
N
HC
(n = 20)
N
IBS
(n = 20)
Pvalue
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
Note. HC = Healthy Controls. IBS = Irritable Bowel syndrome.
Linear regression used to extrapolate high temperatures for some people.
22
CPM efficiency
P < .001
P < .001
23
Scatterplot of CPM with IBS and
Psychological Symptoms with Outlier
24
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
IBS interference Intensity vs ‘Physiological Group’ in
INTENSITY – IBS Interference
IBS Subjects (n=86)
LOW
--
(HRV)
--
HIGH
27
Abdominal Pain in Women with IBS, PMS &
Dysmenorrhea
3.0
2.5
IBS+Dys+PMS
IBS+PMS
IBS+Dys
2.0
Mean Abdominal Pain
IBS Women with
PMS &
dysmenorrhea
report greater
menses-linked
amplification of
abdominal pain
symptoms
1.5
1.0
IBS only
.5
Control
0.0
-10 -9 -8 -7 -6 -5 -4 -3 -2 -1
1
2
3
Days pre-menses / Days post onset
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