IS PELVIC FLOOR MUSCLE TENDERNESS A DISTINCT UROLOGIC CHRONIC PELVIC PAIN SYNDROME (UCPPS) PHENOTYPE?: FINDINGS FROM THE MULTIDISCIPLINARY APPROACH TO THE STUDY OF CHRONIC PELVIC PAIN (MAPP) RESEARCH NETWORK SYMPTOM PATTERN STUDY (SPS)

Abstract

Purpose:

85% of women with interstitial cystitis/bladder pain syndrome (IC/BPS) and men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) have concomitant pelvic floor muscle tenderness (PFT). The significance of this finding is incompletely understood. This study examines PFT among participants in the MAPP Research Network, and its relationship with urologic chronic pelvic pain syndrome (UCPPS) symptom severity, in order to determine whether this is a phenotypic predictor in UCPPS.

Materials and Methods:

Participants in the MAPP Network Symptom Patterns Study (SPS) underwent a standardized pelvic examination (PEX). Trained examiners palpated six locations evaluating the pelvic musculature for PFT. Participants were assigned a 0 to 6 PEX score based on the number of areas with tenderness on PEX. Using regression tree models, PEX scores were divided into low (0–1), mid (2,3,4,5), and high (6). The relationship between PFT and UCPPS symptoms was examined using several validated questionnaires.

Results:

The study cohort consisted of 562 UCCPS participants (375 females and 187 males), and 69 controls. Diagnoses included IC/BPS (n=397), CP/CPPS (n=122), both (n=34), or no diagnosis (n=9). 81% of UCPPS participants had PFT on PEX compared to 9% of controls: 107 (19%) low, 312 (56%) mid, and 143 (25%) high. Participants with higher PFT scores had more severe disease burden (worse pelvic pain and urinary symptoms), worse quality of life, and more widespread distribution of non-pelvic pain.

Conclusions:

UCPPS patients with more widespread PFT have severe pain and urinary symptoms, worse quality of life, and a more centralized pain phenotype.

Introduction:

Urologic Chronic Pelvic Pain Syndrome (UCPPS) includes two conditions; interstitial cystitis/bladder pain syndrome (IC/BPS) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). UCPPS may present with pain in the genitalia and other overlapping urologic and non-urologic symptoms^1,2 and seems to be both peripherally and centrally mediated. Central sensitization of pain is characterized by increased neuronal responsiveness in central pain pathways³ and pelvic floor abnormalities could contribute to this afferent sensitivity in UCPPS.⁴ 85% of these individuals experience concomitant pelvic floor tenderness (PFT) and this reproduces their UCPPS-related pain.^5–7 Studies suggest that PFT may represent a distinct phenotype of UCPPS; however, its correlation with urinary and pain symptoms has only been studied in small cohorts.^7–10

PFT is often present in other disorders including endometriosis, vulvodynia, and anorectal pain.^11,12 UCPPS patients with PFT may benefit from targeted myofascial pelvic health physical therapy/physiotherapy (PHPT). In a randomized controlled trial (RCT) of myofascial PHPT, 59% of IC/BPS subjects with PFT experienced significant improvements in a Global Response Assessment but not in urinary or pain parameters when compared to subjects treated with global therapeutic massage.⁸ However, these subjects were not assessed for widespreadness or severity of PFT. Studies of women with PFT have found correlation with central sensitization on validated questionnaires.^13,14 It is possible that respondents to myofascial PHPT had less widespread involvement, making them better candidates. The current study aims at evaluating how PFT relates to overall UCPPS pain, urinary symptoms, and determine if PFT is a phenotypic predictor of UCPPS. We examined whether PFT serves as a marker of severe pelvic pain or a surrogate for a generalized (centralized) pain.

Methods:

The MAPP Research Network is a multisite group of multidisciplinary investigators aiming to understand the pathophysiology of UCPPS. The current study utilizes data from the second observational cohort study, the MAPP Research Network SPS.¹⁵

The population included men and women with UCPPS and a control cohort recruited from 6 university medical centers. UCPPS participants were assessed weekly through the 1-month run-in period and every 3 months thereafter for 36 months. Inclusion criteria were: UCPPS symptoms present for the last 3 months, age ≥ 18, and response of ≥ 1 on a bladder/prostate/pelvic pain/pressure/discomfort scale during the past 2 weeks.¹⁵ A comparison control cohort (n= 69) was assessed at baseline and 6 months. Data on urological symptoms, pain, COPCs, and psychosocial health were collected using previously validated instruments.^{15 16} For this study, PFT and its association with urinary and pain symptoms was assessed only from the baseline evaluation.

We evaluated urinary symptoms through the Rand Interstitial Cystitis Epidemiology (RICE) case definition, Genitourinary Pain Index (GUPI), Urinary Symptom Severity Score, and American Urologic Association Symptom Index (AUA-SI).¹⁶ Pain symptoms were evaluated using the Pain Severity Score, Symptom and Healthcare Utilization Questionnaire (SYM-Q), Genitourinary Pain Index (GUPI), and Brief Pain Inventory (BPI).¹⁶

Neuropathic pain was assessed using the painDETECT questionnaire. Scores ≤12 indicate neuropathic pain is unlikely, and scores ≥ 13 indicate neuropathic pain. A modified Collaborative Health Outcomes Information Registry (CHOIR) body map was utilized for assessment of pain location. Markers of pain centralization were assessed based on previous work from the MAPP network using the fibromyalgia diagnostic criteria (fibromyalgia-ness), and widespreadness pain index. Elevated scores correspond to altered central pain processing and is a robust predictor of both central sensitization and disability.¹⁷ A median score of ≥ 7 has been adopted to classify nociplastic/centralized pain.^16,17

Quality of life (QOL) measures included the Short form (SF-12) Composite physical health (PCS) and Composite mental health scores (MCS), and the O’Leary-Sant Interstitial Cystitis Symptom and Problem Indices (ICSI/ICPI). The International Physical Activity Questionnaire (IPAQ) was used to assess physical activity during a usual week.¹⁶

COPCs including fibromyalgia (FM), irritable bowel syndrome (IBS), temporomandibular disorders (TMJD), vulvodynia, chronic fatigue syndrome (CFS), and migraine were identified using the Complex Multi-Symptom Inventory (CMSI). Psychosocial factors were assessed with the Hospital Anxiety and Depression Scale (HADS), Coping Skills Questionnaire (CSQ), and Perceived Stress Scale(PSS).¹⁶

Investigators were centrally trained to perform a standardized physical examination (PEX)¹⁸ to quantify PFT at the initial SPS visit. Examiners palpated 6 pelvic floor locations: right and left levator ani (4 sites) and right and left obturator internus (2 sites) in women vaginally (in supine lithotomy in stirrups) and in men transrectally (standing, supported prone over the end of the exam table). (Supplementary material) The investigators chose to perform exams differently in men and women to align with clinical practice norms. The dominant index finger, gloved, with lubricant was used for all exams. Finger pressure was applied at each point to produce discernible movement of the soft tissue. At each location, the examiner asked participants whether they experienced pain with palpation (yes/no) and if the palpation reproduced their UCPPS symptoms. The PEX score was calculated from 0 to 6 depending on the number of sites where participants reported pain with higher scores indicating more pelvic floor involvement.

Statistical Analysis:

We examined how PFT relates to overall UCPPS symptoms at baseline. Regression trees were implemented to determine optimal cut-points on the PEX score to classify subgroups into ordinal groupings ranging from low to severe PFT. We identified measures significantly associated (p<.0001) with the ordinal PEX score. A combined score was derived through exploratory factor analysis (EFA) specifying one factor to produce a single composite score. Regression trees started with the composite score as the target. We split the observations into two groups by choosing the best PEX value for the split. We repeated this process determining the best fit based on average square error and residual sum of squares.¹⁹ Sensitivity analyses was examined using the identified measures individually as the target measures replicating the groupings. (Supplementary figures) From this categorized PEX index, we compared differences by PEX score on baseline demographic and clinical characteristics using Analysis of Variance and χ2 tests for continuous and categorical variables, respectively. Separate from the regression tree categorization, correlation coefficients were derived to quantify associations for the continuous PEX score. Normality of continuous measures was assessed and transformations were applied as needed. Non-parametric Kruskal-Wallis tests were used if normality was not achieved. If k independent associations are examined for statistical significance, the probability that at least one is found to be statistically significant (true type I error) exponentially increases with each test.²⁰ Rothman²¹ states no adjustments are needed for multiple comparisons; however, we recognize the potential of chance finding. With high correlation among many of the measures, rather than perform a Bonferroni adjustment, we set a more stringent level adjusting a standard alpha-level of 0.05 by a factor of 50, for a significance value of p <0.001. To examine gender, we augmented the original models to include an interaction of gender with the PEX score.

Results:

Demographic characteristics are displayed in Table 1. Subjects had a high level of education, and majority were female. Correlation analyses showed significant associations (p<0.0001) of PEX score with the following baseline measures: Pain Severity, Urinary Severity, GUPI-Total Score, Fibromyalgia symptom severity, HAD-S Anxiety, and HAD-S Depression. Regression tree models yielded the following groups: PEX score 0,1 (low, n = 107/562), PEX score 2,3,4,5 (mid, n = 312/562), PEX score 6 (high, n = 143/562). Sensitivity analysis based on pain and urinary severity as outcomes for individual regression tree models yielded the same three-level categorization. Additional sensitivity analysis for each measure in the EFA replicated the low group 100% and the high group 75%. For 25% where high group did not replicate, PEX score 6 could not be separated from score 2,3,4,5 yielding two groups 0,1 versus 2,3,4,5,6. To ensure the cut-points differentiated the groups, we examined if the PEX categories were associated with reproduction of UCPPS symptoms and observed a significant positive trend between increasing symptom severity and the likelihood that participants’ UCPPS symptoms were reproduced (p<0.0001). The prevalence of reproducing participants’ UCPPS symptoms were 24%, 71%, and 85% across low, mid, and high, respectively (all pairwise comparisons <0.008 with a Tukey-Kramer adjusted significance), with similar findings by sex. (Tables 2).

Table 1:

Demographics of MAPP Symptoms Pattern Study Participants

	Urologic Chronic Pelvic Pain Syndrome (UCPPS) (N=562)	CONTROL (N=69)
Site	N (%) / Mean(SD)	N (%) / Mean(SD)
Northwestern	82 (14.6%)	12 (17.4%)
UCLA	93 (16.6%)	13 (18.8%)
Iowa	105 (18.7%)	9 (13.0%)
Michigan	94 (16.7%)	12 (17.4%)
Washington	88 (15.7%)	11 (15.9%)
Washington University of St. Louis	100 (17.8%)	12 (17.4%)
Sex: Female	375 (66.7%)	34 (49.3%)
Race
White	474 (88.3%)	45 (65.2%)
Black	29 (5.4%)	9 (13.0%)
American Indian	3 (0.6%)	0 (0%)
Native Hawaiian	1 (0.2%)	0 (0%)
Asian	6 (1.1%)	6 (8.7%)
Multirace	16 (3.0%)	6 (8.7%)
Other	8 (1.5%)	3 (4.4%)
Ethnicity: Latino/Hispanic	30 (5.3%)	7 (10.1%)
Education
< High School	1 (0.2%)	0 (0%)
High School or GED	38 (7.1%)	4 (5.8%)
Some College	138 (25.7%)	12 (17.4%)
Graduated from College/University	235 (43.8%)	30 (43.5%)
Professional or Graduate degree	125 (23.3%)	23 (33.3%)
Employment
Employed	281 (62.3%)	52 (75.4%)
Unemployed	43 (9.5%)	7 (10.1%)
Retired	82 (18.2%)	8 (11.6%)
Homemaker	11 (2.4%)	2 (2.9%)
Disabled	34 (7.5%)	0 (0%)
Age	45.1 (sd=15.7)	41.0 (sd=14.6)
Diagnosis
IC/BPS	397 (70.6%)	N/A
CP/CPPS	122 (21.7%)	N/A
Both	34 (6.0%)	N/A
Pain Severity	14.3 (sd=5.65)	0.2 (sd=0.81)
Urinary Severity	11.6 (sd=6.22)	2.8 (sd=2.5)
Number of Pain Sites	6.97 (sd=8.37)	0.7 (sd=1.1)
GUPI Score Total	23.8 (sd=8.93)	1.4 (sd=1.8)
# of Chronic Overlapping Pain Conditions	1.2 (sd=5.62)	0.1 (sd=0.24)
Fibromyalgia	29 (5.2%)	0 (0%)
Irritable Bowel Syndrome	210 (40.9%)	1 (1.5%)
Temporomandibular Disorders	147 (27.3%)	0 (0%)
Vulvodynia (women only)	65 (18.7%)	0 (0%)
Chronic Fatigue Syndrome	69 (13.5%)	0 (0%)
Migraine	168 (31.5%)	3 (4.6%)

Table 2:

UCPPS Pelvic Floor Clusters and exam findings

Variable	PEX Low: 0 or 1	PEX Mid: 2,3,4,5	PEX High: 6	p-value
Participants	107	312	143	-
Tenderness Present at Exam Site
Left posterior levator	4 (3.7%)	156 (50.0%)	143 (100.0%)	<.0001
Right posterior levator	3 (2.8%)	154 (49.4%)	143 (100.0%)	<.0001
Left obturator internus	10 (9.3%)	197 (63.1%)	143 (100.0%)	<.0001
Right obturator internus	3 (2.8%)	188 (60.3%)	143 (100.0%)	<.0001
Left anterior levator	7 (6.5%)	191 (61.2%)	143 (100.0%)	<.0001
Right anterior levator	6 (5.6%)	201 (64.4%)	143 (100.0%)	<.0001
Exam reproduces pain or discomfort	26 (24.3%)	221 (71.1%)	121 (84.6%)	<.0001

Overall, 81% (455/562) of UCPPS participants had some PFT (PEX >0); by contrast only 9% (6/69) of controls had PFT. Most UCPPS participants (56%) were in the PEX mid group. The distribution of PEX scores differed some between men and women with 28% of women experiencing pain in all 6 regions as compared to 21% of men. In contrast, among healthy controls, 91% were in the PEX low group, with 87% reporting no tenderness (PEX=0, Table 3).

Table 3:

Healthy Control Pelvic Floor Pain Distribution at Baseline Assessment

Gender	PEX Categories: 0 or 1 (LOW)	PEX Categories: 2,3,4,5 (MID)	PEX Categories: 6 (HIGH)	Total
Male	33 (94.3%)	2 (5.7%)	0 (0.0%)	35 (50.7%)
Female	30 (88.2%)	4 (11.8%)	0 (0.0%)	34 (49.3%)
Total	63 (91.3%)	6 (8.7%)	0 (0.0%)	69 (100%)

Note: Row percentages are inside parentheses.

Severity of urinary and pain symptoms increased in a dose-response fashion across the PEX low, mid, and high groups (Tables 4, 5 and 6). PEX high participants had more urinary symptoms on the ICSI nocturia question, GUPI urinary subscore, and overall Urinary Severity (Table 4). PEX high participants reported more severe pain symptoms, including Pain Severity Composite score, GUPI pain score, BPI, total bodily pain sites, and pain interference with their general activity, work, and relationships (p<0.0001). Increased PEX scores correlated with neuropathic pain characteristics on painDETECT. PEX high had characteristics indicating a more centralized phenotype with more widespreadness on body map, more COPCs, and pain centralizing on the fibromyalgianess score (Tables 5 and 6).¹⁷ Contrasts between women with and without vulvodynia were separately examined and no statistically significant differences were noted. PEX high participants had worse QOL as reflected on the SF12, ICSI, ICPI, AUASI-QOL score, and GUPI-QOL questionnaires (p<0.0001 for all, Table 7). PEX high participants had higher depression and anxiety scores (p < 0.01, Table 6). The correlation of severity of urinary and pain symptoms with PEX groups did not differ by sex. All interaction terms did not achieve statistical significance of p<0.001.

Table 4:

UCPPS Pelvic Floor Clusters and urinary symptoms

Variable	Stat	PEX Categories: 0 or 1 (LOW)	PEX Categories: 2,3,4,5 (MID)	PEX Categories: 6 (HIGH)	p-value	Correlation
Participants		107	312	143	-	-
ICSI - Nocturia	Mean (SD)	1.8 (1.34)	2.0 (1.43)	2.2 (1.41)	0.0338	0.073
RICE: painful bladder filling		59 (55.1%)	200 (64.1%)	107 (74.8%)	0.0046	0.097*
RICE: painful urgency		61 (57.0%)	216 (69.2%)	109 (76.2%)	0.0050	0.153***
RICE: Either painful bladder filling/urgency		77 (72.0%)	261 (83.7%)	133 (93.0%)	<.0001	0.174***
GUPI scale: Pain or discomfort as bladder fills		52 (49.5%)	213 (68.7%)	113 (79.0%)	<.0001	0.146***
Urinary Severity [0–25]	Mean (SD)	8.9 (5.57)	11.9 (6.15)	13.2 (6.23)	<.0001	0.204***
GUPI urinary subscore	Mean (SD)	3.4 (2.52)	5.0 (3.01)	5.7 (2.92)	<.0001	0.235***

Note: Correlation coefficient quantifies the association of the respective variable and the 0 to 6 PEX score. Statistical significance for correlation coefficients:

^*p<0.05

^**p<0.01

^***p<0.001.

Note: ICSI - Interstitial Cystitis Symptom and Problem Indices ; RICE - Rand Interstitial Cystitis Epidemiology, GUPI - Genitourinary Pain Index.

Table 5:

UCPPS Pelvic Floor Clusters and pain symptoms

Variable	Stat	PEX Categories: 0 or 1 (LOW)	PEX Categories: 2,3,4,5 (MID)	PEX Categories: 6 (HIGH)	p-value	Correlation
Participants		107	312	143	-	-
Pain Severity [0–28]	Mean (SD)	11.5 (5.71)	14.3 (5.40)	16.3 (5.28)	<.0001	0.259***
Genitourinary Pain Index -pain subscore	Mean (SD)	9.7 (4.56)	11.7 (4.33)	13.5 (4.30)	<.0001	0.256***
Symptom and Healthcare Utilization Questionnaire (SYM-Q)
Urologic pain [0–10]	Mean (SD)	3.7 (2.22)	4.7 (2.32)	5.2 (2.43)	<.0001	0.192***
Non-urologic pain [0–10]	Mean (SD)	2.6 (2.23)	3.4 (2.57)	4.2 (2.83)	<.0001	0.218***
Brief Pain Inventory(BPI)
Number of Pain Sites [0–76]	Mean (SD)	4.5 (5.40)	7.0 (8.64)	8.7 (9.16)	0.0004	0.163***
Number of Non-Pelvic Pain Regions [0–12]	Mean (SD)	1.7 (1.87)	2.4 (2.55)	3.0 (2.68)	0.0004	0.179***
Symptom severity	Mean (SD)	10.9 (7.27)	14.8 (7.58)	18.1 (8.59)	<.0001	0.286***
Worst Pain Past Week [0–10]	Mean (SD)	4.5 (2.69)	5.7 (2.42)	6.4 (2.34)	<.0001	0.246***
Least Pain Past Week [0–10]	Mean (SD)	1.4 (1.81)	2.2 (2.03)	3.1 (2.61)	<.0001	0.252***
Avg Pain Past Week [0–10]	Mean (SD)	3.0 (2.09)	3.9 (1.99)	4.7 (2.22)	<.0001	0.254***
Current Pain [0–10]	Mean (SD)	2.1 (2.04)	3.2 (2.37)	4.0 (2.61)	<.0001	0.253***
Pain interference	Mean (SD)	14.9 (14.45)	24.2 (17.81)	29.8 (19.27)	<.0001	0.256***
Pain Interfered General Activity	Mean (SD)	2.2 (2.30)	3.7 (2.94)	4.7 (2.99)	<.0001	0.264***
Pain Interfered Mood	Mean (SD)	2.7 (2.56)	4.1 (2.82)	4.7 (3.02)	<.0001	0.220***
Pain Interfered Walking Ability	Mean (SD)	1.5 (2.32)	2.4 (2.88)	3.5 (3.20)	<.0001	0.225***
Pain Interfered Normal Work	Mean (SD)	2.0 (2.34)	3.4 (3.13)	4.3 (3.31)	<.0001	0.229***
Pain Interfered Relationships	Mean (SD)	1.7 (2.25)	3.1 (3.06)	3.8 (3.17)	<.0001	0.231***
Pain Interfered Sleep	Mean (SD)	2.4 (2.65)	3.8 (3.29)	4.5 (3.27)	<.0001	0.203***
Pain Interfered Enjoyment	Mean (SD)	2.5 (2.51)	3.8 (2.99)	4.5 (3.02)	<.0001	0.218***
Pelvic Pain and Beyond	Yes	61 (59.8%)	219 (71.1%)	112 (78.9%)	0.0053	0.125**
no. of genital pain sites on sex-specific genital map	Mean (SD)	1.2 (1.05)	1.3 (1.13)	1.6 (1.16)	0.0184	0.139**
Any Genital Pain	Yes	78 (72.9%)	230 (74.0%)	121 (84.6%)	0.0284	0.118**
Pelvic Floor Index 6 [0–6]	Mean (SD)	0.3 (0.46)	3.5 (1.11)	6.0 (0.00)	<.0001	-
Perineal pain on exam	Yes	14 (13.1%)	71 (22.8%)	76 (53.1%)	<.0001	0.314***
Suprapubic pain on exam	Yes	21 (19.6%)	152 (48.9%)	107 (74.8%)	<.0001	0.364***
PainDetect Score	Mean (SD)	5.8 (4.86)	9.3 (6.35)	11.8 (7.08)	<.0001	0.304***
PainDetect - nociceptive	Yes	93 (86.9%)	225 (72.1%)	78 (54.5%)	<.0001	0.251***
PainDetect - neuropathic	Yes	2 (1.9%)	35 (11.2%)	21 (14.7%)	0.0032	0.144***
Fibromyalgianess Scale 0–31	Mean (SD)	6.0 (4.27)	8.4 (5.29)	9.9 (5.45)	<.0001	0.246***
Pain Centralizing (FM > 7)	Yes	37 (36.3%)	143 (46.4%)	88 (62.0%)	0.0002	0.237***
FM Symptom Severity Score 0–12	Mean (SD)	4.0 (3.08)	5.8 (3.01)	6.5 (3.01)	<.0001	0.264***
Widespread Pain Index 0–19	Mean (SD)	1.9 (2.50)	2.6 (3.28)	3.4 (3.59)	0.0019	0.157***

Note: Correlation coefficient quantifies the association of the respective variable and the 0 to 6 PEX score. Statistical significance for correlation coefficients:

^*p<0.05

^**p<0.01

^***p<0.001

Note: GUPI - Genitourinary Pain Index, Symptom and Healthcare Utilization Questionnaire (SYM-Q), Brief Pain Inventory(BPI).

Table 6:

UCPPS Pelvic Floor Clusters groups and COPCs

Variable	Stat	PEX Categories: 0 or 1 (LOW)	PEX Categories: 2,3,4,5 (MID)	PEX Categories: 6 (HIGH)	p-value	Correlation
Participants		107	312	143	-	-
Chronic overlapping pain conditions (COPC)
FM		1 (1.0%)	15 (4.8%)	13 (9.1%)	0.0154	0.120**
IBS		26 (26.8%)	119 (41.8%)	65 (49.6%)	0.0023	0.140**
TMJD		17 (16.2%)	78 (26.5%)	52 (37.4%)	0.0010	0.178***
Vulvodynia		6 (14.3%)	37 (17.6%)	22 (23.2%)	0.3793	0.098
CFS		5 (5.0%)	42 (14.9%)	22 (17.1%)	0.0166	0.141**
Migraine		17 (16.3%)	98 (33.3%)	53 (39.0%)	0.0005	0.176***
At least 1 COPC [excluding Vulvodynia]		45 (42.1%)	183 (58.7%)	93 (65.0%)	0.0010	0.164***
At least 1 COPC [including Vulvodynia]		47 (43.9%)	193 (61.9%)	97 (67.8%)	0.0004	0.174***
At least 2 COPC [excluding Vulvodynia]		14 (13.1%)	104 (33.3%)	61 (42.7%)	<.0001	0.215***
At least 2 COPC [including Vulvodynia]		16 (15.0%)	112 (35.9%)	67 (46.9%)	<.0001	0.233***
Number of COPC [excluding Vulvodynia]	Mean (SD)	0.6 (0.92)	1.1 (1.22)	1.4 (1.37)	<.0001	0.229***
Number of COPC [including Vulvodynia]	Mean (SD)	0.7 (0.97)	1.2 (1.31)	1.6 (1.47)	<.0001	0.243***
Complex Multi-Symptom Inventory number of Symptoms Endorsed	Mean (SD)	10.5 (6.44)	14.4 (7.43)	17.4 (8.49)	<.0001	0.285***
Hospital Anxiety and Depression Scale: Depression	Mean (SD)	3.9 (3.53)	5.9 (4.71)	6.6 (4.55)	<.0001	0.189***
Hospital Anxiety and Depression Scale:Anxiety	Mean (SD)	6.0 (4.38)	7.4 (4.72)	8.2 (5.01)	0.0016	0.158***
Coping Skills Questionnaire total (0–36)	Mean (SD)	8.9 (7.90)	11.4 (8.18)	12.7 (9.18)	0.0020	0.132**
Perceived Stress Scale Total Score	Mean (SD)	13.0 (7.77)	16.1 (8.17)	17.6 (8.15)	<.0001	0.195***

Note: Correlation coefficient quantifies the association of the respective variable and the 0 to 6 PEX score. Statistical significance for correlation coefficients:

^*p<0.05

^**p<0.01

^***p<0.001

Note: CMSI - Complex Multi-Symptom Inventory, HADS - Hospital Anxiety and Depression Scale, CSQ - Coping Skills Questionnaire , PSS - Perceived Stress Scale, COPC - Chronic overlapping pain conditions, FM – Fibromyalgia, IBS- Irritable Bowel Syndrome, TMJD - Temporomandibular Disorders, CFS - Chronic Fatigue Syndrome.

Table 7:

UCPPS Pelvic Floor Clusters and quality of life

Variable	Stat	PEX Categories: 0 or 1 (LOW)	PEX Categories: 2,3,4,5 (MID)	PEX Categories: 6 (HIGH)	p-value	Correlation
Participants		107	312	143	-	-
Short form (SF-12) Composite physical and mental health scale
SF-12 PCS	Mean (SD)	50.3 (7.76)	45.6 (9.87)	42.2 (10.41)	<.0001	−0.260***
SF-12 MCS	Mean (SD)	47.8 (10.04)	42.6 (10.67)	41.6 (10.65)	<.0001	−0.184***
Interstitial Cystitis Symptom Total	Mean (SD)	7.4 (4.25)	9.3 (4.47)	10.2 (4.47)	<.0001	0.182***
Interstitial Cystitis Problem Total	Mean (SD)	6.3 (4.07)	8.1 (4.06)	9.0 (3.95)	<.0001	0.192***
American Urologic Association Symptom Index	Mean (SD)	11.3 (7.42)	15.0 (8.14)	17.0 (7.88)	<.0001	0.209***
Genitourinary Pain Index - Total	Mean (SD)	19.1 (8.47)	23.9 (8.38)	27.2 (8.93)	<.0001	0.273***
International physical activity questionnaire- 4 ordinal categories
No Exercise		4 (3.8%)	38 (12.2%)	11 (7.7%)	0.0012	−0.133*
Walking Only		22 (20.8%)	98 (31.4%)	48 (33.6%)
No Vigorous Exercise		25 (23.6%)	66 (21.2%)	42 (29.4%)
Any Vigorous Exercise		55 (51.9%)	110 (35.3%)	42 (29.4%)
International physical activity questionnaire- 3 ordinal categories
Walking OR No Exercise		26 (24.5%)	136 (43.6%)	59 (41.3%)	0.0007	−0.139
No Vigorous Exercise		25 (23.6%)	66 (21.2%)	42 (29.4%)
Any Vigorous Exercise		55 (51.9%)	110 (35.3%)	42 (29.4%)
International physical activity questionnaire- No Exercise		4 (3.7%)	38 (12.2%)	11 (7.7%)	0.0257	0.046
Currently Working		70 (73.7%)	186 (62.2%)	81 (58.3%)	0.0481	−0.091

Note: Correlation coefficient quantifies the association of the respective variable and the 0 to 6 PEX score. Statistical significance for correlation coefficients:

^*p<0.05

^**p<0.01

^***p<0.001

Note: GUPI - Genitourinary Pain Index, Interstitial Cystitis Symptom and Problem Indices (ICSI/ICPI), IPAQ - International physical activity questionnaire, Short form (SF-12) Composite physical and mental health scale, AUA - American Urologic Association Symptom Index.

Discussion:

A standardized PEX was utilized to evaluate PFT in UCPPS participants. This pelvic floor exam has been previously published, and this study highlights its utility in clinical practice for assessing UCPPS.¹⁸ Individuals with UCPPS in this study had a high prevalence of PFT (81% mid to high PEX category) consistent with previous studies of men with CP/CPPS and women with IC/BPS compared to the low PEX scores in the control group.^5–7 Men with CP/CPPS have more pain with transrectal palpation of the levator muscles than healthy controls,²² and CP/CPPS subjects with PFT have more severe symptoms.⁷ Similarly, two studies evaluating women with chronic pelvic pain (CPP) vs healthy controls found that those with CPP had higher total musculoskeletal tender point pain scores and intensity of pain.^10,23

In the MAPP SPS study, symptom severity correlated with the PEX score for bladder pain and urinary symptoms in both men and women. A previous study of 833 subjects presenting with pelvic floor disorder symptoms, also found a correlation between PFT and degree of symptom bother.⁹ These findings support the importance of clinicians’ assessment of PFT to identify patients with more severe UCPPS and possible centralization. Pelvic floor abnormalities, specifically afferent sensitivity, may contribute to the pathophysiology of pain and urinary symptoms in UCPPS.⁴ This is supported by previous work showing abnormalities in the functional connectivity of the Supplementary Motor Area (SMA) in the brain, which contains motor neurons that control pelvic floor muscle activity^24–26 indicating that afferent changes may be contributing to their symptoms.

Individuals in the PEX high group were more likely to have features of centralized pain (fibromyalgia questionnaire, widespreadness on body map), higher likelihood of concomitant COPC, more psychological burden and more severe non-pelvic pain. (Table 5 and 6) Pelvic floor dysfunction and/or pain appears to be associated with increased symptom severity and poorer QOL not only in UCPPS but also in other chronic pain syndromes. Consistent with pain centralization, women with fibromyalgia have a higher prevalence of pelvic floor symptoms than controls, and their symptoms are associated with more depression, sleep disturbances, and lower QOL.²⁷

Multimodal therapies are important in UCPPS treatment.^28,29 Physical therapists tailor treatments based on types of pain. For nociceptive pain they perform both local tissue focused interventions like manual therapy/desensitization techniques (ex. stretching, touch) and exercise(coordination and strengthening).³⁰ The majority of MAPP participants had evidence of nociceptive pain on the painDETECT. In participants with neuropathic pain features, a higher percentage had increased PFT on examination, consistent with the concept that regional or pelvic sensitization can be a feature of neuropathic pain in UCPPS. Individuals with UCPPS with neuropathic pain and PFT may benefit from treatments targeting pelvic pain sensitization such as local nerve blocks at the pudendal nerve or trigger point injections of the levator muscles, or PT directed care such as manual release of adhesions gliding and movement pattern training.³⁰

Lastly, this study may shed light on findings from prior RCT for PHPT versus global therapeutic massage. Nonrespondents, may have had centralization of pain, explaining why they did not respond as well to PHPT; however, that domain was not captured in the RCT.⁸ In this study, we categorized participants based on degree of PFT and noted increasing symptom severity with higher PEX scores. One could hypothesize that the PEX high group, given their more centralized features, may require therapy directed at their centralized pain in addition to their pelvic floor. In contrast, patients with mild or moderate pelvic floor dysfunction might benefit from targeted PHPT.

Limitations of this study include potential variability regarding the examination and assessment of PFT. As a mitigating strategy, all study sites and personnel were centrally trained by a pelvic floor physical therapist and mock patients on the methodology of the examination, the pressure applied and the assessment of the responses.¹⁸ In addition, males and females were examined differently (vaginally versus rectally). The authors recognize that a rectal exam may differ due to the nature of examination through the anal sphincter versus estrogen-sensitive vaginal mucosa. However, this was a previously validated technique intended as a simple, sex-specific examination to assess PFT.¹⁸ The extended exam was not used as we focused specifically on PFT prevalence. This study did not examine for other co-morbid factors that may contribute to PFT such as low back pain, however COPCs were considered. We did not evaluate participants’ responses to PHPT. Furthermore, to simplify the PEX across multiple study sites, the severity of pelvic floor tenderness (e.g., 0–100 pain ratings during PEX) was not recorded. Future studies are needed to evaluate how the PEX relates to changes in symptoms over time and to define which subgroups are most likely to benefit from PHPT versus more centralized therapies.

Conclusions:

The presence and extent of PFT on PEX in UCPPS correlates with urinary and pain severity and quality of life in a dose-dependent fashion. This suggests a role for PHPT in patients with more localized muscle tenderness. In contrast, patients with pain in all areas of the pelvic floor, have more severe pain and urinary symptoms and may represent a more ‘centralized’ phenotype. Patients with severe PFT and centralized pain may derive greater benefit from systemic therapies addressing central nervous system dysregulation. Our findings indicate a need for more detailed phenotyping of the pelvic floor in UCPPS that could inform studies evaluating the effectiveness of different interventions.