International Journal of

Environmental Research
and Public Health

Review
New Insights about Chronic Pelvic Pain
Syndrome (CPPS)
Keren Grinberg 1, *, Yael Sela 1 and Rachel Nissanholtz-Gannot 2
1 Department of Nursing, Faculty of Social and Community Science, Ruppin Academic Center,
40250 Emek-Hefer, Israel; Yaels@[Link]
2 Department of Health Systems Management, Ariel University, 40700 Ariel, Israel; rachelni@[Link]
* Correspondence: Kereng@[Link]; Tel.: +972-9-8983056; Fax: +972-9-8983832




Received: 30 March 2020; Accepted: 21 April 2020; Published: 26 April 2020


Abstract: Background: Chronic pelvic pain syndrome (CPPS) is one of the common diseases in
urology and gynecology. CPPS is a multifactorial disorder where pain may originate in any of
the urogynecological, gastrointestinal, pelvic musculoskeletal, or nervous systems. The symptoms
of CPPS appear to result from an interplay between psychological factors and dysfunction in the
immune, neurological, and endocrine systems. The aim of this article was to present new insight
about CPPS in order to raise awareness of nursing and medical staff in the identification and diagnosis
of the syndrome and to promote an appropriate treatment for each woman who suffers from CPPS.
Methods: A literature review about the factors associated with CPPS and therapeutic interventions
for CPPS was conducted. Results: CPPS represents a chronic pain syndrome that combines anatomic
malfunction of the pelvic floor muscles with malfunction of pain perception linked with psychological
and cognitive factors. Conclusions: The therapeutic interventions in CPPS cases should, consequently,
follow a multidisciplinary approach.

Keywords: chronic pelvic pain syndrome (cpps); therapeutic interventions; musculoskeletal pain;
urology; gynecology

1. Overview on Women with CPPS

Chronic pelvic pain syndrome (CPPS) is defined as pain located in the pelvic area that lasts
over six months and is severe enough to limit functioning, unrelated to menstrual cycle, pregnancy,
local trauma, or pelvic operations. This syndrome is one of the diseases shared by urology and
gynecology [1–3]. Its frequency is between 3% and 10%, and it is more frequent among women [4–6].
The costs of treating CPPS were estimated at about USD 880 million annually [7]. About 15% of women
reported loss of work days and 45% reported decreased work efficiency [5,8].
This integrative review was aimed at presenting an interdisciplinary overview on women CPPS
patients. Therefore, a descriptive review of the literature on the pathogenesis, risk factors, diagnosis,
and treatment strategies was performed.

2. Materials and Methods

Search Strategy
A systematic literature search, using PubMed, Medline, Embase, PsychINFO, and Web of Science
databases, was performed by two authors with the terms and phrases: “Chronic pelvic pain”, “painful
bladder syndrome”, “provoked vestibulodynia”, “musculoskeletal pain”, and “therapeutic interventions”.
Only publications in the most recent decade were searched for, and the date of publication was
set from 1st January 2010 to 31st January 2020. A manual search was conducted to identify additional

Int. J. Environ. Res. Public Health 2020, 17, 3005; doi:10.3390/ijerph17043005 [Link]/journal/ijerph
 Int. J. Environ. Res. Public Health 2020, 17, x FOR PEER REVIEW 2 of 12
Int. J. Environ. Res. Public Health 2020, 17, 3005 2 of 11
Only publications in the most recent decade were searched for, and the date of publication was
set from 1st January 2010 to 31st January 2020. A manual search was conducted to identify additional
potential
potentialeligible
eligiblestudies
studiesfrom
from thethe reference
reference lists of the the eligible
eligible articles.
[Link]
authors reviewed
reviewed thethe
search
search [Link],
strategy. Overall,we
weselected
selected 9292 publications.
publications. In Inthis
thisreview,
review,we wetried toto
tried provide
provide ananoverview
overview
of of a largeand
a large andcomplex
complextopic
topic toto provide
provide indications
indications regarding
regardingthe themanagement
management of of
CPPS
CPPS patients,
patients,
since
since managementrequires
management requiresaaholistic
holistic approach
approach in in order
orderto toprovide
providepatients
patientswith
withproper
proper care. Painful
care. Painful
bladder
bladder syndrome(PBS)
syndrome (PBS)and
andprovoked
provoked vestibulodynia
vestibulodynia (PVD) (PVD)are aresubgroups
subgroupsofofCPPS CPPS[1]. Diagnosis
[1]. Diagnosis
of of
PBSPBSis isbased
basedon oncomplaints
complaintsthatthat include
include anan urgent
urgentand/or
and/orfrequent
frequentneedneedtotourinate
urinateand andpain that
pain that
disrupts daily activities and reduces quality of life (such as interrupted sleep, difficulty
disrupts daily activities and reduces quality of life (such as interrupted sleep, difficulty with sexual with sexual
intercourse,depression,
intercourse, depression, oror anxiety)
anxiety) [1,9–11].
[1,9–11]. Manual
Manualexamination
examinationofof the pelvis
the pelvismaymayfind tension,
find tension,
rigidity, and sensitivity of the pelvic floor muscles or myofascial trigger points. PVD refers to pain at
rigidity, and sensitivity of the pelvic floor muscles or myofascial trigger points. PVD refers to pain at
the entrance of the vagina, known as the vestibule, experienced as sharp or burning pain that lasts at
the entrance of the vagina, known as the vestibule, experienced as sharp or burning pain that lasts at
least three months [12–14]. The diagnosis criteria for PVD may include severe pain when touched or
least three months [12–14]. The diagnosis criteria for PVD may include severe pain when touched or
when vaginal penetration is attempted, soreness located in the vestibule without similar soreness in
when vaginal penetration is attempted, soreness located in the vestibule without similar soreness in
adjacent tissues, and ruling out other factors (infection, inflammation, skin disease, etc.) [13]. PVD is
adjacent tissues, and ruling out other factors (infection, inflammation, skin disease, etc.) [13]. PVD is
diagnosed with a Q-tip test. A doctor assesses pain by touching the vestibule with a cotton swab
diagnosed
[12,14]. Most with patients
a Q-tip test. A doctor
report assesses
pain during pain intercourse
sexual by touchingtothe vestibule
the point thatwith a cotton
it is swab [12,14].
impossible, and
Most patients report pain during sexual intercourse to the point that it is
mention pain during gynecological examinations [15], while inserting a tampon, or with directimpossible, and mention pain
during
contactgynecological
such as whileexaminations
bicycle riding, [15], while inserting
horseback riding, orawearing
tampon,tight
or with direct
clothing contact such
[12,14,16–18] as while
(Figure
bicycle
1). riding, horseback riding, or wearing tight clothing [12,14,16–18] (Figure 1).

[Link]
Figure Symptomsand
and diagnosis
diagnosis of
of subgroups
subgroupsofofchronic
chronicpelvic
pelvicpain
painsyndrome (CPPS).
syndrome (CPPS).

AAnumber
number of mechanisms
mechanismshave havebeen suggested
been suggestedas theaspathophysiological basis of CPPS:
the pathophysiological (1) CPPS:
basis of An
infection process, but no conclusive evidence has been found and antibiotic treatment
(1) An infection process, but no conclusive evidence has been found and antibiotic treatment is is ineffective;
(2) A neurogenic
ineffective; inflammation
(2) A neurogenic that includesthat
inflammation localincludes
chemicallocal
changes [1,7]; (3)
chemical Hypoxia.
changes A (3)
[1,7]; disrupted
Hypoxia.
A blood flowblood
disrupted to theflow
pelvic area,
to the reduced
pelvic area,micro-vascular density ofdensity
reduced micro-vascular the bladder’s submucosa
of the bladder’s layer,
submucosa
followed by decreased perfusion [19] is supported by clinical improvement following
layer, followed by decreased perfusion [19] is supported by clinical improvement following hyperbaric hyperbaric
treatment
treatment [20–22];and
[20–22]; and(4)
(4)Weakness
Weaknessor or cramps
cramps ofof the
the pelvic
pelvicfloor
floormuscles
muscles[13,23].
[13,23].None
None of of
thethe
above
above
have been mentioned as the sole cause of the syndrome, and it is estimated that these mechanisms
have been mentioned as the sole cause of the syndrome, and it is estimated that these mechanisms
interact. A common explanation is that, for an unknown reason, the glycosaminoglycan (GAG) layer
interact. A common explanation is that, for an unknown reason, the glycosaminoglycan (GAG)
that coats the mucosa of the bladder and vagina is damaged. This damage leads to a chain of nerve-
layer that coats the mucosa of the bladder and vagina is damaged. This damage leads to a chain of
cell-level processes that culminate in a neurogenic inflammation and mast cell activation [24]. The
nerve-cell-level processes that culminate in a neurogenic inflammation and mast cell activation [24].
GAG layer, which is an impermeable barrier of urine solutes, becomes permeable. The infiltration of
The GAG layer, which is an impermeable barrier of urine solutes, becomes permeable. The infiltration
of solutes into the submucosa irritates the nerve endings and creates heightened inflammation
agents: vasoactive intestinal peptides, substance P, and acetylcholine [16,24]. As a result, activated
Int. J. Environ. Res. Public Health 2020, 17, 3005 3 of 11

mast cells secrete histamines that widen the blood vessels and generate a local inflammation [25].
The inflammation irritates the C-fibers and causes increased release of more inflammation agents,
which in turn cause additional damage and the formation of fibrosis on the bladder [21,25] or in the
vagina [15,16,24,26].
The literature has indicated that PBS and PVD are chronic pain diseases [27], which involve
dysfunction of the general pain system, and are not just a pelvic dysfunction. Concerning PBS, research
findings demonstrated hypersensitivity in response to experimental pain among these women [28]
expressed by allodynia and hyperalgesia in the projected pain area above the pelvis [21,29,30]. Women
with PVD, in comparison to healthy women, presented increased sensitivity to pain in body areas
distant from the genital area [31–36] conveyed by allodynia and hyperalgesia. Harlow and Stewart
(2003) [37] found that PVD women demonstrated disruptions of pain modulation as well as increased
central sensitization processes, but little is written in the literature about this dimension. So far,
only two imaging studies examined central pain processes in PVD women, and both found high
activation in response to painful experimental stimulation. One study [38] found increased activation
of the several brain areas, amygdala, thalamus, anterior cingulate cortex (ACC), prefrontal cortex
(PFC), and insula, in response to pressure stimulation of the vulva. A second study [39] found
activation and hyperactivity in the same brain areas, in comparison to healthy subjects, in response
to pressure stimulation of a distant area or of the vulvar area. Imaging studies that examined CPPS
patients in general reported reduced grey matter in the ACC [40]. The relative decrease of grey matter
volume, which indicates neuroanatomic changes, was found in other chronic pain conditions such
as chronic back pain, inflammatory bowel syndrome (IBS), migraines, and phantom pains [41–43].
Furthermore, it is possible that structural changes are related to depression and other emotional aspects
that accompany chronic pain [42,44,45], because areas such as the ACC have a significant role in
processing emotional information in general and that related to chronic pain specifically.
These findings, which indicate hypersensitivity of the pain system among women with PBS and
PVD, raise the possibility that a dysfunction of the central pain system is at the core of CPPS. However,
it is not clear whether a peripheral defect that causes chronic pain affects pain processing on the level
of the central nervous system and creates changes in the perception and processing of pain [46] or,
alternatively, a dysfunction of pain processing and modulation causes the development of chronic pain
in CPPS women [1,24].
The existence of other, especially idiopathic, chronic pain diseases in CPPS patients (such as
fibromyalgia and IBS) supports the notion that a dysfunction of the central pain system is the source of
the pain. For example, among patients with medically unexplained symptoms, 19% met diagnostic
criteria for both chronic pelvic pain and fibromyalgia [47]. CPPS and fibromyalgia share many
unexplained characteristics and key symptoms, including pain as a prominent symptom, comorbidity,
and localized and systemic conditions [48]. Women with overlapping pain syndromes may have
more widespread symptoms and evidence of central pain sensitization [49]. Studies revealed that
women with both fibromyalgia and chronic pelvic pain demonstrate increased widespread pain
intensity, anxiety, and depression [50,51]. Presence of pelvic pain is associated with increased overall
pain severity and fibromyalgia disease impact. It may be that changes in the effectiveness of pain
processing, control, and regulation processes, which characterize women with CPPS, affect the severity
of the symptoms and are involved in the response to interventions [1,52]. These variables and their
relationship with the severity of CPPS and the effect of the treatment should be examined in future
[Link] to other syndromes in which the pathogenesis process is unknown [53], the treatment
of CPPS is varied (Figure 2) and includes:

1. Cognitive behavioral therapy (CBT) includes deep breathing, learning techniques to control
(contract and relax) pelvic muscles, and bladder training. Bladder training teaches patients to
control the disease (for example, by prolonging periods between urinations by using various
mind distracting methods) and has been proven to increase urine volumes and decrease urination
frequency [20,22,24];
Int. J. Environ. Res. Public Health 2020, 17, x FOR PEER REVIEW 4 of 12

Int. J. Environ. Res. Public Health 2020, 17, 3005 4 of 11

mind distracting methods) and has been proven to increase urine volumes and decrease
urination frequency [20,22,24];
2. Medications
Medications includeinclude drugs
drugs such as tricyclides and sodium pentosanpolysulfate (which inhibits
histamine
histamine release
release from from mastmast cells)
cells) oror drugs
drugs that
that are injected into the bladder (for example,
glycosaminoglycans that
glycosaminoglycans that are part are part of the bladder’s natural protection layer; resiniferatoxin and
capsaicin
capsaicin that
that bind
bind to to nerve-ending
nerve-ending receptors and desensitize pain fibers; and botolonium toxin
that
that inhibits
inhibits thethe secretion
secretion of inflammatory
inflammatory agents such as substance p and nerve growth factor
and prevents
and prevents higher tonus of pelvic muscles). Most Most drugs
drugs tested on CPPS patients showed good
short-term
short-term results
results [30],
[30], but
but only
only a few were found to have have long-term
long-term results
results [20,22].
[20,22]. There is
evidence of some success in response to hormone
evidence of some success in response to hormone therapy administered therapy administered orally, by ointment, or
by
by injection
injection[54–56].
[54–56].The Thevarious
variousdrugs
drugsare areadministered
administered systemically
systemically or or
locally, and
locally, andthey
theycancan
be
classified
be classifiedby their
by theiraction mechanisms:
action mechanisms: (1) Improvement
(1) Improvement of pain ofregulation (assuming
pain regulation the pain
(assuming is
the
neuropathic) by drugs that inhibit reuptake of noradrenaline
pain is neuropathic) by drugs that inhibit reuptake of noradrenaline and serotonin, and and serotonin, and improve
functioning
functioning of of the
the downward
downward pain-processing conduits [57,58]; (2) Preparations that delay nerve
conduction velocity by
conduction velocity byusing
usinganesthetics;
anesthetics; these
these have
have beenbeen tested
tested by aby a number
number of studies,
of studies, and
and were
were found to have limited effectiveness [59]; and (3) Drugs that
found to have limited effectiveness [59]; and (3) Drugs that inhibit production of prostaglandins, inhibit production of
prostaglandins,
or steroid-type or steroid-type
drugs, drugs,due
administered administered due to the
to the assumption thatassumption
CPPS has that CPPS has an
an inflammatory
inflammatory source
source [41] (Table 1); [41] (Table 1);
3.
3. Surgery
Surgery is is aa last resort when
last resort when traditional
traditional treatment
treatment has has failed.
failed. Some
Some surgeries
surgeries of of PBS
PBS women
women
destroy the bladder nerves and others implant electrodes that electrically
destroy the bladder nerves and others implant electrodes that electrically stimulate the nerve stimulate the nerve
roots. However, this treatment, as is the case in other chronic diseases,
roots. However, this treatment, as is the case in other chronic diseases, provides only a partial provides only a partial
solution,
solution, andand is is not
not based
based on on empiric
empiric guidelines.
guidelines. Therefore,
Therefore, the the mechanisms
mechanisms at at the
the root
root ofof CPPS
CPPS
must be understood to identify which women are suitable for
must be understood to identify which women are suitable for this kind of treatment [20,60]. this kind of treatment [20,60].
Women
Women with with PVD PVDare aresometimes
sometimesoffered
offereda vestibulectomy,
a vestibulectomy, in which
in which thethe mucous
mucous membrane
membrane of
of the
the vagina,
vagina, the the
hymen, hymen,andand somesome glands
glands in the
in the areaarea are removed
are removed [54,61–63];
[54,61–63]; andand
4.
4. Myofascial physical therapy (MPT) is considered safe,
Myofascial physical therapy (MPT) is considered safe, is recommended for the is recommended for syndrome,
the syndrome,and isandan
is an important stage of therapeutic intervention for the pelvic floor (see
important stage of therapeutic intervention for the pelvic floor (see the following section) [2,64–67]. the following section)
[2,64–67].

Figure 2. Multidisciplinary treatment options for CPPS.

Int. J. Environ. Res. Public Health 2020, 17, 3005 5 of 11

Table 1. Possible drug treatment interventions for CPPS.

Potential Medication Action Mechanisms Therapeutics Intervention

Improves pain regulation; improves
Tricyclic antidepressants; Inhibit reuptake of noradrenaline
functioning of the downward
sodium pentosapolysulfate and serotonin
pain-processing conduits
Bind to nerve-ending receptors and
Resiniferatoxin; capsaicin Delays nerve conduction velocity
desensitize pain fibers
Inhibits the secretion of inflammatory Administered due to the assumption
agents such as substance p and nerve that CPPS has an inflammatory
Botulinum toxin
growth factors; inhibits production of source; prevents higher tonus of
prostaglandins pelvic muscles
Some success in response to
hormone therapy; pain is related
Hormone therapy Releases hormone agonists
to the menstrual cycle and
hormonal changes

3. Myofascial Physical Therapy (MPT)

Physical treatment of the pelvic floor includes, in addition to exercises to strengthen the pelvic floor,
biofeedback treatment and electric muscle stimulation, or bladder training. Pelvic myofascial manual
therapy (MMT) is performed by an expert physical therapist, and its aim is to release a myofascial
constraint at painful trigger points. The treatment is based on making soft tissue more elastic, easing
articular rigidity in the area, releasing and stretching shortened muscles, and strengthening weak
muscles in order to restore the balance of musculoskeletal components, to allow optimal painless
functioning, and to reduce discomfort [68,69]. In addition, this treatment could improve blood flow to
the pelvic area; reduced blood flow has been suggested as one of the mechanisms at the basis of the
syndrome [30,64,68,70–72]. Pelvic floor exercises and bladder training could improve coordination
and functioning of pelvic floor muscles [65]. Manual treatment of myofascial trigger points has been
proven to reduce pain [55,73–75]. Although this treatment is very common and accepted as a method
with beneficial results, the mechanisms that occur following this intervention are still unclear, and we
still do not have the tools to identify the patients for whom this intervention would be clinically
effective [73,74].
The rationale for treating CPPS patients with MMT is based on pathological findings in the pelvic
floor area of these patients, which attest to malfunction of the pelvic floor muscles, and include points
sensitive to pain as well as additional musculoskeletal abnormalities in the pelvic floor area [68,76,77].
These findings cause pain and other symptoms characteristic of CPPS. Indeed, MMT has been found
to reduce pain severity; hence, it would seem that MMT has significant clinical impact among CPPS
patients [78]. Additional verification of MPT’s efficacy was found in a study that proved that focused
MPT improved the clinical condition and pain of 60% of women with CPPS compared to improvement
in 20% of women with CPPS who received general massage [64]. The fact that physical treatment was
found to be effective in pelvic pain diseases raises questions about its importance for CPPS patients,
which (local or systemic) factors can predict its success, and whether it can affect these factors [78].

4. Psychological Factors and Pain

The experience of pain and its processing involve many psychological and cognitive variables such
as emotions, cognition, focus, a sense of control, adjustment, behavior patterns, interactions between
the patient and the therapist, as well as beliefs and expectations [79]. A key variable involved in the
experience of pain is pain catastrophizing, which is defined as exaggerated negative orientation toward
aversive stimulation. Pain catastrophizing includes three dimensions: rumination on the painful
stimulation, magnification of the threat inherent in the painful stimulation, and a self-perception of
helplessness to control the pain [80,81]. People with a high degree of pain catastrophizing attribute great
severity, threat, or catastrophic consequences to pain [82]. Research has indicated a strong relationship
Int. J. Environ. Res. Public Health 2020, 17, 3005 6 of 11

between the pain catastrophizing variable and reports of enhanced clinical and experimental pain,
great mental distress, depression, limited functioning, higher post-op reports of pain, lower response
to medical treatments, and greater use of medical services [32,52,72,83,84]
Among women suffering from PBS, a relationship was found between the degree of pain
catastrophizing and the severity of the pain and number of symptoms [83,84]. Granot and Lavee
(2005) [85] noted that whereas no difference in pain catastrophizing in response to pain stimulation to
the arm was found between women with and without PVD, the pain catastrophizing scale (PCS) rating
of pain during intercourse correlated with higher pain rating among women with PVD. Other studies
found that higher pain catastrophizing was reported by women with genital pain in comparison
to healthy women [72], and there was a correlation between the rating of pain catastrophizing and
increased cerebral activity in the prefrontal brain areas responsible for pain modulation or focus [18].
Regarding anxiety, it was found that women with PBS suffered higher anxiety levels (which
related to the severity of the symptoms) than did healthy women [83,86]. In addition, the severity
of the pain of women with PVD was linked to higher anxiety, beliefs of fear-avoidance, and pain
catastrophizing, which indicates that the severity of genital pain could be linked to emotional stress
that is characterized by negative expectations such as fear or anxiety [24,52]. Another study reported
that apart from the pain problem, additional issues (such as sexual problems) were linked to the anxiety
of these women [87].
The fear-avoidance (FA) model was suggested to help understand the psychological processes
that occur in response to pain. Accordingly, it can be assumed that among women who suffer from
dyspareunia, catastrophic thoughts, fear, and muscle tension form avoidance of painful situations,
which creates disability and depression [72]. Anxiety symptoms may reflect an increase in negative
feelings, which at later stages (according to the FA model) increase pain catastrophizing [88], and these
eventually intensify fear and avoidance of pain [88,89]. It was suggested that anxiety and fear of pain
coupled with negative expectations cause the patient to focus on her illness and pain, which affect her
sexual response and ability to cope with pain [24]. This supposition was corroborated by a study that
found that the perception of pain and anxiety play a role in PVD pathogenesis and contribute to the
development of hypersensitivity to pain among these women [85]. Similarly, Heddini and colleagues
(2012) [14] found that low levels of anxiety and pain catastrophizing were related to less pain during
intercourse and improved sexual functioning.
Another key psychological factor that affects perception of pain is depression. Depression is
defined as a complex neurological and cognitive reaction to loss or absence, and as a health condition,
detrimentally affects thoughts, emotions, and the ability to function in everyday life. The American
Psychiatric Association defined depression as a desperate mood and loss of interest or pleasure
in almost all activities that caused pleasure before the event [90,91]. Among women with CPPS,
the frequency of depression is higher compared to women who do not suffer from the syndrome [92,93].
Furthermore, among these women, the level of depression correlates with sensitivity to experimental
pain and duration of the illness [34]. In light of this, it was suggested that depression has a significant
contribution to the severity of CPPS [93].
An additional psychological variable that is common among chronic pain patients is somatization [94].
Somatization is described as a disorder in which the patient complains of a number of somatic symptoms
(multisymptomatic) with no organic evidence of pathology. In fact, these symptoms appear as a result of
psychological problems and are also characterized by pain [95]. High levels of somatization were found
among women with PBS [83], which correlated with increased sensitivity to experimental pain [1,85],
was related to the severity of the symptoms, and predicted less therapeutic success [69,96]. It is
known that psychological variables such as somatization, depression, and anxiety serve as important
predictors of clinical results and the success of surgical interventions in syndromes of chronic pain [97].
However, no studies were found that examined the contribution of somatization to predicting the
success of myofascial physical therapy for women suffering from CPPS.
Int. J. Environ. Res. Public Health 2020, 17, 3005 7 of 11

5. Conclusions
In view of the above findings and due to the combination between hypersensitivity to pain and
psychological factors among CPPS women, and since the pain in this syndrome affects sexual functioning
and intimacy, it is important to examine the contribution of these factors, whether on their own or in
interaction with physical factors, to the severity of CPPS and the success of treatment. Furthermore,
the therapeutic intervention in CPPS cases should, consequently, be follow a multidisciplinary approach.
In summary, the literature indicates that CPPS represents a chronic pain syndrome that combines
anatomic malfunction of the pelvic floor muscles with malfunction of pain perception linked with
psychological and cognitive factors (involved in, for example, pain processing). Earlier diagnosis
and support may help women to manage the syndrome and its impact on their activities of daily
living. CPPS has physical, psychological, and sexual health impacts on women’s lives and those of
their partners. Nurses and doctors are ideally placed to support women with CPPS. Furthermore,
the therapeutic intervention in CPPS cases should, consequently, be multidisciplinary. This group of
women should be investigated in RCT (Randomized Controlled Trial) studies to examine the factors
that affect the syndrome and how to cope with it.

Author Contributions: K.G., Y.S., and R.N.-G. performed the data collection, wrote and edited the manuscript.
All authors have read and agreed to the published version of the manuscript.
Funding: This study had no funding.
Acknowledgments: The authors would like to thank Ruth Moont for reviewing and editing this manuscript.
Conflicts of Interest: The authors declare no conflict of interest.

Abbreviations
CPPS Chronic pelvic pain syndrome
PBS Painful bladder syndrome
PVD Provoked vestibulodynia
GAG Glycosaminoglycan
ACC Anterior cingulate cortex
CBT Cognitive behavioral therapy
MPT Mechanical pain threshold
MMT Myofascial manual therapy
IBS- Inflammatory bowel syndrome
PCS Pain catastrophizing scale
FA Fear-avoidance

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