Urologic chronic pelvic pain Jeannette M. Potts ,

PAIN 153 (2012) 755–758
Topical review
Urologic chronic pelvic pain
Jeannette M. Potts a,⇑, Christopher K. Payne b
900 Welch Road, Suite 202, Palo Alto, CA 94304, USA
Stanford University Medical School, 300 Pasteur Drive, A260, Stanford, CA 94305-5118, USA
Urologic chronic pelvic pain (UCPP), primarily interstitial cystitis (IC)/painful bladder syndrome (PBS) in men and women, and
chronic prostatitis (CP)/chronic pelvic pain syndrome (CPPS) in
men, were initially regarded as bladder and prostate diseases. Decades of research have failed to establish infectious or other clear
etiologies; in fact, bladder/prostate inflammation is uncommon.
Most patients are best characterized as having a functional somatic
syndrome (FSS). Current theory focuses on hyperesthesia/allodynia
and pelvic floor muscle dysfunction (PFD).
tomatology, and high counts can be found in asymptomatic men
[34]. In a study of 122 asymptomatic men with elevated prostate-specific antigen levels, 42% had abnormally elevated white
blood cell counts in their prostatic secretions [29].
A recent meta-analysis of CP/CPPS treatments demonstrated
modest, nonsignificant, responses to antibiotics [4]. Treatments
targeting prostate or bladder neck disorders that can cause LUTS,
such as alpha-blockers, were also analyzed. The pooled response
rates favored alpha-blockers alone or in combination with antibiotics. However, the authors stated this alleged benefit ‘‘may be
overinflated, given the evidence for publication bias,’’ found in
the study. A definitive NIDDK-sponsored trial showed no difference
between alfuzosin (alpha-blocker) and placebo (34.8% vs. 33.6%,
P = .90) [25]. A study of 100 CP/CPPS patients receiving sequential
monotherapies for 1 year, including ‘‘prostato-centric’’ therapies
such as antibiotics, alpha-blockers, and anti-androgens showed
moderate improvement in 30% of cases and significant improvement in only 19% [24]. There is also no convincing evidence that
surgical therapy directed at the prostate is effective for CP/CPPS
1. Introduction
2. Chronic prostatitis/chronic pelvic pain syndrome
‘‘Prostatitis’’ accounts for 8% of urologist visits [11]. More than
90% of these patients have genital/pelvic pain, with or without
lower urinary tract symptoms (LUTS) and sexual dysfunction, with
symptoms exceeding 3 months in the absence of demonstrable
infectious etiology [19].
In 1995, a National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) consensus panel established the prostatitis
classification system (Table 1). The most common form, Category
3 or chronic (nonbacterial). Prostatitis was revised to include the
term chronic pelvic pain syndrome ‘‘to reflect the uncertainty about
whether the [symptoms] in fact originate from the prostate gland’’
[21]. In 2002, a subsequent expert panel assembled in Giessen,
Germany concluded that CP/CPPS is not due to infection because
symptoms and bacterial culture results are not correlated [34].
Symptom-free healthy individuals and CP/CPPS patients have an
8% incidence of positive localization cultures [23]. The panel recommended using antibiotics only after 2 positive localization cultures identified the same organism [32].
Although CP/CPPS pathophysiology continues to elude explanation, current theories include atypical bacterial infection, nanobacterial colonization, voiding dysfunction, and bladder sphincter
dyssynergia (nonrelaxation of the external urinary sphincter during micturition), abnormal intra-prostatic pressure in men, pelvic
floor myalgia, and emotional disorders [31]. Little evidence suggests prostatic inflammation is characteristic of the disease. The
presence or absence of inflammatory cells in expressed prostatic
secretions or semen has not been shown to correlate with symp⇑ Corresponding author. Tel.: +1 440 409 2272.
E-mail address: [email protected] (J.M. Potts).
3. Interstitial cystitis/painful bladder syndrome
As with CP/CPPS, the cardinal symptom of IC/PBS is pain, with
associated lower urinary tract symptoms such as frequency, urgency, and/or nocturia. Clemens et al. reported in 2005 that only
0.2% of women in a U.S. managed care population were diagnosed
with IC/PBS [8], despite a prevalence of symptoms of 6% to 11% [9].
For unknown reasons, the disorder is far less common in men. Patients are most commonly affected in the third to fifth decade of
life, greatly affecting their peak productive years.
For most of the 20th century IC was diagnosed cystoscopically
by the presence of Hunner’s ulcers: discrete, red, bleeding areas
on the bladder wall [18]. Hunner’s ulcers are uncommon, however,
and a broader syndrome was recognized when Messing and Stamey described the ‘‘early diagnosis’’ of IC based on cystoscopic
identification of glomerulations (small petecchial hemorrhages)
occurring after bladder distention [22]. Diagnostic criteria have
evolved over time (Table 2) and the importance of glomerulations
is currently questioned. Cystoscopy is not a required diagnostic
test in the latest American Urology Association guidelines [17].
A minority of IC/PBS patients have evidence of an end organ
abnormality. Biopsy samples from the 10% of IC/PBS patients with
Hunner’s ulcers [16] and severely affected bladders show denuded
0304-3959/$36.00 Ó 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
J.M. Potts, C.K. Payne / PAIN 153 (2012) 755–758
appropriate to consider the bladder symptoms in these patients
as a manifestation of a complex neuromuscular–psychosocial disorder, consistent with characteristics of FSS.
Table 1
NIH/NIDDK prostatitis classification.
Category 1
Category 2
Category 3
Category 4
Acute bacterial prostatitis
Chronic bacterial prostatitis
Chronic abacterial prostatitis/
Chronic pelvic pain syndrome
Asymptomatic inflammatory
} 5% to 7% of cases
95% of cases
4. Urologic chronic pelvic pain as a functional somatic
epithelium with severe inflammation. The bladder capacity of
these patients is almost always markedly reduced under anesthesia. In contrast, the majority of patients diagnosed with IC/ PBS
have few objective findings during examination under anesthesia.
Cystoscopy is typically entirely unremarkable; the bladder capacity is generally normal; there may or may not be glomerulations
after distention; and biopsies show little or no inflammation
[20]. In addition, there is little evidence that IC is a progressive disease [33], or that patients with nonulcerative disease progress to
ulcer formation [12].
The most accepted theory about the pathophysiology of IC/PBS
is that deficiencies in the glycosaminoglycan layer produce an
inappropriately permeable bladder epithelium. This would allow
toxic and noxious urine constituents to leak back into the bladder
wall, create inflammation and pain [26]. However, there is no conclusive evidence that the glycosaminoglycan layer is abnormal in
IC patients and no conclusive evidence that the epithelium is
abnormally permeable.
As with CP/CPPS, treatment of IC/PBS has been generally unsatisfactory. Anecdotal reports suggest success with various pharmacotherapy strategies, but when Hanno et al. [15] critically reviewed
the published data on oral and intravesical therapies almost all was
of poor quality (evidence Level 4 and 5, recommendation grades C
or lower). Pentosan polysulfate, approved by the Food and Drug
Administration for IC and intended to repair the glycosaminoglycan layer, has been extensively studied in randomized controlled
trials. Although generally better than placebo, the overall response
rate is less than 40%. The highest recommendation was for amitriptyline, which received a B grade based on Level 2 evidence. However, amitriptyline is widely used in patients with many types of
FSS and is in no way specific for the bladder pain. Dimethylsulfoxide bladder instillations were the only effective organ-based therapy, also receiving a B with Level 2 evidence. Radical surgical
therapy has occasionally been successfully used, almost always
in patients with objectively severe disease, and even then there
can be persistent and/or recurrent pain. Surgery is not indicated
for patients who are objectively less affected. It is therefore most
The first systematic exploration of the connection between
UCPP and other disorders was reported by Alagiri et al. in 1997
[2]. The most common diseases in the IC populations studied were
allergies, irritable bowel syndrome (IBS), and sensitive skin. Clauw
et al. examined cohorts of patients with FM, patients with IC, and
healthy controls, and found that IC patients shared many characteristics with fibromyalgia (FM) patients [7]. IC patients were much
more likely than controls to have tender points and to report a
variety of symptoms including fatigue, musculoskeletal symptoms,
gastrointestinal symptoms, and cardiopulmonary symptoms.
In 2001, Potts introduced the notion of CP/CPPS as a consequence of a more general FSS [30]. This study showed that 65%
of CP/CPPS patients expressed features and characteristics of functional somatic disorders. Within this patient cohort, the following
overlapping features were revealed: IBS (35%), chronic headache
(36%), FM (5%), nonspecific rheumatological symptoms (21%), and
psychological disturbances (48%). This observation is most compelling when taken in the context of the extremely low prevalence of
FSS in the general population (4%–8%) [5]. Similarly, a twin control
study demonstrated the aggregation of overlapping syndromes
among the 127 individuals diagnosed with chronic fatigue syndrome (CFS) [1]. When compared with their nonfatigued co-twin,
there was a significantly higher prevalence of FM, IBS, chronic
abacterial prostatitis, pelvic pain, and IC in the CFS twin.
Self-reported medical problems were compared between 463
CP/CPPS patients and 121 controls including gastroenterology, cardiovascular, neurological, lymphatic, infectious, and psychological
evaluations [28]. The CP/CPPS group reported a dramatically higher
incidence of co-morbidities (P < .008). Mental health disorders
among male and female patients with UCPPS are common. Using
tools such as the Patient Health Questionnaire to identify depression or panic disorder, Clemens et al. identified mental disorders
in 13% of the CP/CPPS cases and 4% of male controls (odds ratio = 2.0, P = .04), and in 23% of IC/PBS cases and 3% of female controls (odds ratio = 8.2, P = .001) [10]. Patients reported significantly
higher use of medications for anxiety, depression, or stress compared with controls.
The economic impact of CP/CPPS is significant. Calhoun et al.
found patients with CP/CPPS incurred annual direct and indirect
costs of $4397 per person [6]. Other researchers discovered that
the difference in health care expenditures between CP/CPPS patients and typical HMO patients was because of medical problems
unrelated to CP [35]. This observation would support the tendency
NIH = National Institutes of Health; NIDDK = National Institute of Diabetes, Digestive and Kidney Diseases.
Unknown incidence, as this condition is recognized only as incidental histological
finding of biopsy or prostatectomy or as leukocytospermia detected during infertility evaluations/semen analysis.
Table 2
IC/PBS definitions.
NIDDK (1988)
ICS (2002)
ESSIC (2008)
SUFU (2009)
AUA (2011)
Hunner’s ulcer or glomerulations plus pain
Painful bladder syndrome (PBS): ‘‘the complaint of suprapubic pain related to bladder filling, accompanied by other symptoms such as increased
daytime and night-time frequency, in the absence of proven urinary tract infection or other obvious pathology.’’
IC requires ‘‘typical cystoscopic and histological features.’’
Referred to as bladder pain syndrome: pressure or discomfort perceived to be related to the bladder accompanied by at least one other urinary
An unpleasant sensation (pain, pressure, discomfort) perceived to be related to the urinary bladder, associated with lower urinary tract symptoms
in the absence of infection or other identifiable causes.
Endorsed the SUFU definition, above.
IC = interstitical cystitis; PBS = painful bladder syndrome; NIDDK = National Institute of Diabetes, Digestive and Kidney Diseases; ICS = International Continence Society;
ESSIC = European Society for Study of Interstitial Cystitis (or the International Society for the Study of Bladder Pain Syndrome); SUFU = Society of Urodynamics and Female
Urology; AUA = American Urological Association.
J.M. Potts, C.K. Payne / PAIN 153 (2012) 755–758
for these conditions to aggregate as overlapping syndromes of FSS.
Using different methodology, Payne et al. found that the annual direct medical costs for patients with a diagnosis of IC were $8420
compared with $4169 for matched controls [27].
with FSS are warranted to improve patient care and to reduce
the burden to the health care system.
5. Pelvic floor dysfunction—an overlooked characteristic of
Jeannette M. Potts: no conflict of interest. Christopher K. Payne:
Astellas (consultant), Allergan (consultant), Medtronic (clinical
trial investigator).
6. Approach to the patient
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First, the clinician must acknowledge that the cause of these
disorders is unknown; it is of course possible that future research
will define a specific etiology but at the present time exhaustive efforts to obtain a diagnosis are inappropriate and often counterproductive. Once a reasonable effort has been made to exclude
treatable conditions, testing should be limited. The ESSIC investigators have presented a useful list of ‘‘confusable disorders’’ for IC/
PBS that might be considered in evaluating such patients [36].
Most can be eliminated by a careful history, physical examination,
and urine studies. In select patients cystoscopy, imaging, and urodynamic testing may be useful but these are rarely needed initially
and empiric treatment is most appropriate. First line therapy includes behavioral therapy and stress management. Second line
treatments include pelvic floor physical therapy, pain management, amitriptyline, cimetidine, hydroxyzine, or pentosan polysulfate and bladder instillations (dimethylsulfoxide, heparin, and/or
As with other FSS, emphasis should be placed on recovering
and/or preserving function rather than attempts to cure or eliminate all pain. Specific goals should be set regarding an individual
patient’s ability to work, attend school, care for children, exercise,
participate in community activities, or function in a sexual role. At
the same time, it is reasonable to hope and aim for complete remission of symptoms as long as the focus is on the specific goals.
Finally, it is important to recognize that multimodal therapy
will most likely be required to optimally treat most patients;
new therapies should be introduced 1 at a time and critically evaluated before changing or adding a second therapy. Polypharmacy
is to be avoided to the greatest degree possible.
Possible definable causes outside the urinary tract, such as pelvic floor dysfunction, have not been adequately investigated [37].
In a case series of men previously unresponsive to prostato-centric
modalities, 72% responded favorably to specialized pelvic floor
physiotherapy [3]. A recent NIDDK-sponsored pilot study randomizing UCPP patients to targeted physical therapy or global massage
demonstrated a statistically significant difference in improvement
among patients who received physical therapy [13].
In a follow-up study using the same design but limited to 81
women with IC/PBS, the global response rate was 59% in those randomized to myofascial physical therapy compared with 26% randomized to global massage (P = .0012) [14]. Of 9 studies
performed over a decade by the NIDDK cooperative clinical trial
groups, these are the only 2 positive results. The role of pelvic floor
dysfunction (PFD) is clearly an important avenue for further
Conflicts of interest statement
UCPPS are prevalent conditions causing major morbidity and
expense to the health care system. Two decades of research has
shown that end-organ infection or inflammation is uncommon. Given the current state of knowledge about UCPPS, we propose that
they are best considered as FSS and not as a urological condition. A
logical approach focused on individualized therapy for patients
J.M. Potts, C.K. Payne / PAIN 153 (2012) 755–758
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