Mapping of Pain Phenotypes in Female Patients with Bladder Pain
Syndrome/Interstitial Cystitis and Controls
Dean A. Trippa,*, J. Curtis Nickela, Jennifer Wonga, Michel Pontarib, Robert Moldwinc,
Robert Mayerd, Lesley K. Carre, Ragi Doggweilerf, Claire C. Yangg, Nagendra Mishrah,
aQueen’s University, Kingston, ON, Canada;bTemple University, Philadelphia, PA, USA;cHofstra University School of Medicine, New Hyde Park, NY, USA;
dUniversity of Rochester, Rochester, NY, USA;eUniversity of Toronto, Toronto, ON, Canada;fUniversity of Tennessee, Knoxville, TN, USA;gUniversity of
Washington, Seattle, WA, USA;hJivraj Mehta Hospital, Ahmedabad, India;iUniversity of Copenhagen, Herlev, Denmark
EUROPEAN UROL OG Y 62 (2012) 1188–1194
available at www.sciencedirect.com
journal homepage: www.europeanurology.com
Accepted May 9, 2012
Published online ahead of
print on May 18, 2012
Quality of life
Background: Many bladder pain syndrome/interstitial cystitis (BPS/IC) patients report
body diagram, pain-associated adjustment factors, or the impact of pain in multiple
body areas on patients’ quality of life (QoL).
Objective: Compare and contrast pain in BPS/IC patients and controls using a whole-
body diagram (visible body areas). Examine the association between patient adjustment
factors and greater number of body pain areas (pain phenotypes).
Design, setting, and participants: Validated questionnaires were collected from diag-
nosed, tertiary-care, outpatient, female BPS/IC patients (n = 193) and age-matched
controls (n = 115). Scales included a body pain area diagram, demographics/history,
pain severity, BPS/IC symptoms, pain, depression, catastrophizing, and QoL.
Outcome measurements and statistical analysis: Cross-tabulation and analysis of vari-
ance models addressed the patient and control differences.
Results and limitations: Patients reported more pain than controls in all reported body
areas. Four pain phenotypes were created based on increasing counts of body locations
(BPS/IC only, BPS/IC + plus 1–3 additional locations, BPS/IC plus 4–9, BPS/IC ?10).
Patients reported more body pain locations, pain, urinary symptoms, depression,
catastrophizing, and diminished QoL than controls. The increased-pain phenotype
was associated with poorer psychosocial adjustment and diminished physical QoL,
but catastrophizing and low scores for mental QoL remained stable across all patient
groups. This study was cross-sectional, relying on correlation-based analyses, thus
causality cannot be established.
Conclusions: Patients reported numerous systemic pain symptoms outside the areas
associated with the bladder/pelvic region, and increased numbers of body pain sites
were associated with poorer patient outcomes (ie, pain severity, depression). This study
illustrates the significant negative impact of pain on patient adjustment in BPS/IC. These
findings suggest that clinicians carefully consider pain location distributions and the
potential impact of body pain phenotypes during patient evaluation and treatment
# 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.
* Corresponding author. Departments of Psychology, Anesthesiology, and Urology, Humphrey Hall,
62 Arch Street, Queen’s University, Kingston, Ontario K7L 3N6, Canada. Tel. +1 613 533 6955;
Fax: +1 613 533 2499.
E-mail address: email@example.com (D.A. Tripp).
0302-2838/$ – see back matter # 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.eururo.2012.05.023
Bladder pain syndrome/interstitial cystitis (BPS/IC) has
been described as a ‘‘chronic pelvic pain, pressure, or
discomfort perceived to be related to the urinary bladder,
with at least one other urinary symptom, such as persistent
urge to void or urinary frequency’’ [1,2]. BPS/IC pain is mild
to moderate , but for many it is constant, severe, and
usually associated with bladder filling . Low back pain,
dyspareunia, and premenstrual pain flares are also com-
monly reported . BPS/IC patients suffer from multiple
(eg, irritable bowel syndrome, fibromyalgia) [6,7]. Approxi-
mately two-thirds of patients suffering from BPS/IC report
more than two pain locations , with abdominal pain
being most often reported .
Our previous BPS/IC analysis correlated pain, quality of
life (QoL), and psychosocial adjustments with other
associated conditions , but no studies have examined
BPS/IC body pain locations and these associations using a
whole-body diagram independent of other comorbid
diagnoses. This is the first study using whole-body pain-
phenotype mapping in patients and controls with regard to
QoL and psychosocial factors, providing an enriched
understanding of the BPS/IC pain experience.
2.Patients and methods
The case-control design of this study, including patient populations and
recruitment from the nine participating centers, has been published .
Patients fulfilled the diagnostic criteria described in the US National
Institutes of Health Interstitial Cystitis Database Study  and the
definition described at the US National Institutes of Health Urological
Chronic Pelvic Pain Consensus Symposium . Although not available
at the time, most patients would have fulfilled the criteria for diagnosis
of BPS/IC outlined in the recently published American Urological
Association guidelines  as well as European Society for the Study
of Interstitial Cystitis and European Association of Urology definition of
BPS [1,2]. Female controls were recruited from the general population by
advertisement and included in the study when no self-identified BPS/IC
diagnosis was confirmed.
Study participants answered questions about their age, ethnic back-
ground, relationship status, education, occupation status, and BPS/IC
diagnosis and its duration.
Patients and controls completed the Interstitial Cystitis Symptom Index
and Problem Index (ICSI/ICPI), an eight-item questionnaire assessing
symptom severity and the extent to which symptoms were problematic
during the last month .
Condition-specific symptom questionnaires
The Short-Form McGill Pain Questionnaire (SF-MPQ)  consists of
15 pain descriptors. Scores can be totaled or scored on subscales of
Pain and quality of life
sensory (eg, throbbing, shooting) and affective (eg, tiring-exhausting,
fearful) descriptors, with higher scores indicating greater pain. In
addition, a whole-body diagram  was included. The diagram depicts
the anterior and posterior view of the human body. Participants placed a
mark in as many locations as they had experienced pain in the last 3 mo.
Pain locations were quantified using a body grid system and a scoring
transparency to identify 45 distinct areas in the body diagram (Fig. 1,
Table 1) . The Medical Outcomes Study Short Form (SF-12) QoL
questionnaire is a 12-item measure of health-related QoL. The items are
combined, weighted, and scored on twoscales to determinephysicaland
mental health composite scores .
Patients and controls completed the Center for Epidemiologic Studies
Depression Scale (CES-D), a 20-item self-report measure of depressive
symptomatology during the past week; higher scores indicate more
severe symptoms . Study subjects also completed the Pain
Catastrophizing Scale (PCS) , a 13-item self-report measure that
examines negative cognitive patterns of patient rumination, magnifica-
tion, and helplessness about their perceived ability to manage their pain.
After receiving Ethics Board approval, female urology patients suffering
with BPS/IC and community-based female controls were contacted by
telephone or letter to determine participation. Following affirmative
contact, the informed consent and the packet of questionnaires were
mailed to the participant. Patients and controls were asked to read and
0 – 14.4%
14.5 – 28.9%
29.0 – 43.4%
43.5 – 57.9%
58.0 – 72.4%
72.5 – 87.0%
19191 19 91
2 262 26
200 02 20
27 7 7 72
Fig. 1 – Pain location reports across controls and bladder pain syndrome/
interstitial cystitis patient phenotypic pain groups.
E UR O P E A N U R OL O GY 62 ( 2 01 2 ) 1 1 8 8 – 1 1 9 4
return a signed copy of the consent and the questionnaires by postage-
paid mail. Data collection occurred over 2 mo.
The number of patients enrolled in the initial case-control study provided
was random. Missing data, <20% for any scale item across all measures,
was replaced using a standardized intraparticipant means-imputation
procedure  in 21 cases, <7% of the final sample. Following the item-
as missing. All analyses used a list-wise deletion procedure. Pain location
frequencies were dichotomized into present or absent, as endorsed on a
whole-body diagram. Contingency analyses across patients and controls
pain locations they reported: (1) primary BPS/IC pain site only, (2) BPS/IC
pain site and 1–3 additional locations, (3) BPS/IC pain and 4–9 additional
locations, and (4) BPS/IC pain site and ?10 pain locations. The primary
BPS/IC region included the bladder area, lower abdominal area, and lower
back . One-way analysis of variance (ANOVA) examined differences in
affective and sensory pain, urinary symptoms and problems, depressive
symptoms, catastrophizing, and QoL across the pain-phenotype groups.
catastrophizing, depression, and the IC total score were non-normally
distributed. Variables were successfully transformed using a square root
transformation and ANOVA models were run with both transformed and
Table 1 – Pain location comparisons between patients with bladder pain syndrome/interstitial cystitis (BPS/IC) versus controls*
Control, %BPS/IC, %
Head and neck
 Facial, R front
 Facial, L front
 Head, L back
 Head, R back
 Neck to clavicle area, front
 Neck to clavicle area, back
Shoulder, arm, hand areas
 Shoulder/chest, R front
 Shoulder/chest, L front
 Upper arm to elbow, R front
 Upper arm to elbow, L front
 Lower arm from elbow to wrist, R front
 Lower arm from elbow to wrist, L front
 Palm of the hand and fingers, R
 Palm of the hand and fingers, L
 Upper shoulder to the spine, L back
 Upper shoulder to the spine, R back
 Upper arm to elbow, L back
 Upper arm to elbow, R back
 Lower arm from elbow to wrist, L back
 Lower arm from elbow to wrist, R back
 Top of the hand and fingers, R front
 Top of the hand and fingers, L front
Torso, pelvic, buttock areas
 Breast to bottom of ribcage, R front
 Breast to bottom of ribcage, L front
 Abdomen, R frontz
 Abdomen, L frontz
 Uterus, vagina, bladderz
 Upper back, scapula region, L back
 Upper back, scapula region, R back
 Lower back, Lz
 Lower back, Rz
 Pelvis and buttocks, L backz
 Pelvis and buttocks, R backz
Lower body areas
 Thigh and knee, R front
 Thigh and knee, L front
 Calf, R front
 Calf, L front
 Top of foot, R front
 Top of foot, L front
 Thigh and knee, L back
 Thigh and knee, R back
 Calf, L back
 Calf, R back
 Bottom of foot, L back
 Bottom of foot, R back
L = left, R = right.
*Numbers in brackets in left column correspond to section of the body pain map (Fig. 1).
yBonferroni correction in set at p < 0.001.
zPain locations constituting the primary BPS/IC pain site.
EUROPEAN UR OLOGY 62 (2012) 1188–1194
nontransformed data . The summary of findings was identical for the
Games-Howell statistic , used to contrast groups, was applied and
indicated no differences between the transformed and nontransformed
data. For clarity of interpretation, the nontransformed data arepresented.
SPSS v.20 (IBM Corp., Armonk, NY, USA) was used for analyses.
A total of 315 females participated. Five patients were
excluded because their symptoms resolved. Data from the
remaining 310 participants were examined for entry
accuracy and missing values. Patients (n = 193) reported a
mean age of 49 yr (SD: ?14.9), 89% identified themselves as
Caucasian, and 45% graduated with a university degree or
higher. Controls (n = 117) reported a mean age of 48 yr
(SD: ?13.51), 82% identified themselves as Caucasian, and 54%
graduated with a university degree or higher. There were no
differences in age (p = 0.42) and education (p = 0.30) between
(p = 0.001)with55%ofpatientsworkingfulltime,23%disabled,
and 18% retired, compared to 77% of the controls working,
3% disabled, and 15% retired.
3.1. General pain
months in any body location. A larger proportion of patients
reported pain versus controls (100% vs 60%; p < 0.001).
Patients reported greater frequency of pain in almost all
body areas compared to controls (Fig. 1). A significantly
greater proportion of patients, compared to controls,
reported pain in both sides of the face and back of the
neck, with greater frequency also noted in back of the head
greater frequency of pain in the upper shoulder to the spine,
withgreater frequencyinotherareas, such astheupper arm
to the elbow and the lower arm to the wrist (Table 1).
Further, significantly more frequent pain in the abdomen,
bladder area, upper back, lower back, pelvis, and buttocks
were reported, with elevated frequency of pain in the
breasts to the bottom of the ribcage (Table 1). In the lower
body (ie, legs, feet), patients reported significantly more
pain than controls in the front and back of both thighs and
knees and in the back of the right calf, with greater
frequency of pain reported in the front and back of the left
calf and bottom of the right foot (Table 1).
Of the 193 patients, 27% (n = 52) reported pain in the
primary BPS/IC site (ie, vagina, lower abdomen, lower back,
pelvis, and buttocks) only. As shown in Fig. 2, 23% (n = 44) of
1–3 additional locations, 24% (n = 46) reported pain in 4–9
additional locations, and 26% (n = 51) reported pain in ?10
0 – 14.4%
14.5 – 28.9%
29.0 – 43.4%
43.5 – 57.9%
58.0 – 72.4%
72.5 – 87.0%
262 26 262 2 27 2727 7 7 27
30303 3 30 0
BPS/IC ONLY BPS/IC+(1-3)BPS/IC+(4-9)BPS/IC (10+)
Fig. 2 – Pain location reports across bladder pain syndrome/interstitial cystitis (BPS/IC) patients by phenotypic pain groups: pain reported in the BPS/IC
region only, in the BPS/IC region plus an additional 1–3 areas (BPS/IC + [1–3]), an additional 4–9 areas (BPS/IC + [4–9]), or an additional I10 areas (BPS/IC
E UR O P E A N U R OL O GY 62 ( 2 01 2 ) 1 1 8 8 – 1 1 9 4
additional locations. There were no differences between
controls and patients in terms of age or across any of the
body pain-mapping comparisons (p = 0.862).
3.4.Patient measures across pain-location phenotypes
All BPS/IC pain-phenotype groups reported more severe
sensory pain than controls (p < 0.001). While patients who
had pain at the BPS/IC site only reported similar pain to
patients with one to three additional locations, patients
reporting more than three locations reported greater
sensory pain (Fig. 3). Similarly, all patient groups reported
greater affective pain than controls (p < 0.001). No differ-
ence was found in affective pain between patients reporting
BPS/IC site only and those with one to three or four to nine
additional locations, but patients with more pain sites
reported greater affective pain (Fig. 3).
and symptoms scales were highly correlated (r = 0.84) .
Patients reported more total symptoms than controls
(p < 0.001), but no differences were found between
BPS/IC patient phenotypes (Fig. 3).
Interstitial cystitis symptoms and problems
All BPS/IC pain-phenotype groups reported more catastro-
phizing than controls (p < 0.001). However, no significant
differences were reported for catastrophizing across phe-
notyped groups (Fig. 3).
The BPS/IC pain-phenotype groups reported being
depressed more often than controls (p < 0.001) with
depression increasing as the number of body pain sites
increased. Patients who reported pain at the BPS/IC site and
?10 additional pain locations reported significantly greater
depression than those with pain in the BPS/IC site only
Controls reported a higher physical QoL than all patient
groups (p < 0.001) (Fig. 4). Patients with pain in the BPS/IC
site only reported better physical QoL thanthe other patient
groups. There was poorer mental QoL reported by patients
versus controls (p < 0.001), but no differences between the
BPS/IC phenotyped groups.
Patterns of body-pain mapping showed that 73% of BPS/IC
patients reported pain outside the primary BPS/IC site.
Patients reported pain in the primary BPS/IC pain locations
more often than controls but also reported pain in the head
and neck; shoulders, arms, and hands; torso; pelvic region
and buttocks; and legs and feet.
Patients’ pain severity was associated with pain pheno-
types: Reporting pain in multiple locations was associated
with more affective and sensory pain. BPS/IC and several
seemingly associated chronic pain syndromes (ie, irritable
bowel syndrome, fibromyalgia) have been studied previ-
ously [7,21–24], and it has been suggested that the pain of
BPS/IC may be due to centrally mediated nociception rather
than a visceral nerve abnormality involving only the
bladder [7,21]. The pain distribution in patients with pain
mediated mechanisms are involved, rather than a periph-
eral visceral nerve abnormality. It becomes obvious, then,
that at least in these patients experiencing pain at multiple
body sites, therapy directed only at the bladder is doomed
to failure  and that systemic pharmacologic agents with
central effects (eg, tricyclic antidepressants, gabapenti-
noids) will likely provide more overall benefit. Considering
the present findings, the diagnosis and treatment of BPS/IC
must include identification and management of pain
outside the pelvis.
While differences in BPS/IC disease-specific symptoms
and associated factors (catastrophizing) were found across
all patient groups versus controls, the severity of these
parameters was not different across pain phenotypes. There
Fig. 3 – Mean pain scores for each phenotypic pain group. Higher score
indicates greater severity. BPS/IC = bladder pain syndrome/interstitial
cystitis; ICSI/ICPI = Interstitial Cystitis Symptom Index and Interstitial
Cystitis Problem Index; PCS = Pain Catastrophizing Scale; CES-D = Center
for Epidemiologic Studies Depression Scale.
Fig. 4 – Mean quality of life (QoL) score in each phenotypic pain group.
Higher scores indicate better QoL. QoL-PCS = Physical Composite Score
Short Form; QoL-MCS = Mental Composite Score Short Form.
EUROPEAN UR OLOGY 62 (2012) 1188–1194
were no differences across phenotypes in patient age,
education, and duration of symptoms, so these factors
cannot explain the lack of variance in urinary symptoms,
bother, or catastrophizing. Since previous studies show that
catastrophizing can vary by age and with longer duration of
pain , the addition of a longitudinal study on changes in
pain and catastrophizing may be needed to understand its
influenceovertime inpatients withBPS/IC painphenotypes.
Depression was elevated in patients compared with
controls, and was higher in the group reporting pain at the
BPS/IC site with ?10 additional locations compared with
patients reporting pain only in the primary BPS/IC location.
These data support suggestions that the severity of depres-
sion is associated with greater pain [7,27–29] as well as
diminished health-related QoL and poorer prognosis [7,30].
Patients reported diminished physical QoL versus con-
trols and patients in the increased-pain phenotype group
reported the lowest QoL scores. Mental QoL was also
diminished in patients compared with the control group.
QoL has a longstanding negative association with BPS/IC
pain [7,31–33], but this study is the first to illustrate QoL
deficits across pain-location phenotypes. This is the first
evidence that the number of comorbidities associated with
a pain site is associated with diminished physical QoL in
BPS/IC. Interestingly, mental QoL was not associated with
reported pain locations. This may be a pattern similar to
catastrophizing in that duration of symptoms may be a
suppressing factor for any effects visible over time.
This study was cross-sectional and relied primarily on
correlation-based analyses; thus, causality cannot be estab-
lished . The current study needs to be replicated in
several samples to enhance the generalizability of our
pain. The body areas of the pain-mapping diagram in this
study are not identical to dermatomes (eg, T6–8 would run
across areas 12–15 of the body diagram), nor did we map
syndromes . An analysis of this type might have further
clinical ramifications in improving our understanding of
BPS/IC pain. Generalizing these findings is cautioned against
because this study sample was female only, primarily
Caucasian, educated, and drawn from tertiary care centers.
Men suffering from BPS/IC, patients early in symptom onset,
or patients of other ethnicities may manifest different
to examine prevalence, symptoms, and QoL in racial and
minority groups suffering from painful bladder symptoms,
Clemens et al.  reported that symptoms were equally
common in Caucasian, African American, and Hispanic
persons. The age and education of the participant were
limits study generalization. Thus the currentresults may not
apply to younger patients, older patients, or those with
replication in such groups.
This study has documented the existence of pain-
location phenotypes and their associated psychosocial
impact. Physicians managing patients with BPS/IC are
advised to direct attention to pain outside the pelvis
because therapy focused on only genitourinary pain and
systemic medical approach to pain management. Moreover,
this study also suggests that psychosocial therapies with
particular emphasis on negative appraisals and depression
should be considered. There are emerging psychosocial
therapies for patients with pelvic pain, including cognitive
behavioral strategies in male genitourinary pain [35,36].
Future research may also consider mapping the associations
of pain and associated comorbid conditions or objective
pathophysiologic findings (ie, cystoscopy, biopsy, and/or
body. Patients with BPS/IC experience pain in more areas of
the body and this is associated with higher pain levels,
catastrophizing, depressive symptoms, BPS/IC symptoms/
problems, and diminished physical QoL when compared to
controls. For patients with BPS/IC, having multiple pain sites
is associated with increased depression, symptoms, and
poorer physical QoL. Physicians should plan individualized
therapeutic strategies with an emphasis on depression and
pain outside the bladder for patients with more numerous
and distinct pain-location BPS/IC phenotypes.
Author contributions: Dean A. Tripp had full access to all the data in the
study and takes responsibility for the integrity of the data and the
accuracy of the data analysis.
Study concept and design: Tripp, Nickel, Mayer, Pontari.
Acquisition of data: Wong, Moldwin, Mishra, Yang, Doggweiler, Nordling,
Analysis and interpretation of data: Tripp, Wong, Nickel.
Drafting of the manuscript: Tripp, Nickel, Wong, Pontari, Moldwin, Mayer,
Carr, Doggweiler, Yang, Mishra, Nordling.
Critical revision of the manuscript for important intellectual content: Tripp,
Statistical analysis: Tripp, Wong.
Obtaining funding: None.
Administrative, technical, or material support: Tripp, Nickel, Wong,
Pontari, Moldwin, Mayer, Carr, Doggweiler, Yang, Mishra, Nordling.
Supervision: Tripp, Nickel.
Other (specify): None.
Financial disclosures: Dean A. Tripp certifies that all conflicts of interest,
including specific financial interests and relationships and affiliations
relevant to the subject matter or materials discussed in the manuscript
(eg, employment/affiliation, grants or funding, consultancies, honoraria,
stock ownership or options, expert testimony, royalties, or patents filed,
received, or pending), are the following: None.
Funding/Support and role of the sponsor: None.
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