{"paper_id":"c2ec5958-f3ab-4bae-9978-a2b4a3f02a22","body_text":"ISSN: 2398-2799\nFront Womens Healt, 2018         doi: 10.15761/FWH.1000154\nReview Article\nFrontiers in Women’s Health\n Volume 3(4): 1-9\nAn odyssey through chronic pelvic pain in women\nIbrahim I Bolaji* and Ka yan Shirley SZE\nDepartment of Obstetrics and Gynaecology, Hull York Medical School Diana, Princess of Wales Hospital, NLaG NHS Foundation Trust, UK\nAbstract\nThe five common conditions encountered in patients with chronic pelvic pain (CPP) consist of endometriosis, interstitial cystitis, pelvic floor dysfunction, irritable \nbowel syndrome and pudendal nerve entrapment. The most unrecognised cause of CPP is the latter which affects only 4% of patients.\nA thorough work up of patient’s pain is necessary prior to subjecting patients to any intervention including surgery as over 40% of gynaecological laparoscopies are \nperformed for long standing pelvic pain. CPP is of multi-source origin which makes it difficult in formulating a plan of care for patients with this condition. If one \nsource of the pain is detected, it is important to rule out other conditions that may also be contributing. \nAll practitioners treating patients with CPP have to be knowledgeable about all of the potential causes of pelvic pain and addressing only the commonest cause like \nendometriosis is not adequate.\n*Correspondence to: Ibrahim I Bolaji, Department of Obstetrics and \nGynaecology, Hull Y ork Medical School Diana, Princess of Wales Hospital, \nNLaG NHS Foundation Trust, Scartho Road, Grimsby DN33 2BA, UK, Tel: 01-\n472-874-111; Fax: 01-472-875-452; E-mail: iibolaji@yahoo.com\nKey words: Chronic pelvic syndrome, endometriosis, bladder pain syndrome, \ninterstitial cystitis, pelvic floor dysfunction, irritable bowel syndrome and pudendal \nnerve entrapment\nReceived: August 23, 2018; Accepted: September 20, 2018; Published: \nSeptember 24, 2018\nSources and Selection Criteria\nWe performed a Medline and Embase search using the MeSH \nterms, evidenced based guidelines and published consensus statements \nfrom 1992 to date, limited to publications in English and to chronic \npelvic pain in women. Our search strategy was very broad using a \ncombination of MeSH, text-words and appropriate word variants of \ncauses of chronic pelvic pain including chronic pelvic pain syndrome, \nendometriosis, bladder pain syndrome, interstitial cystitis, pelvic floor \ndysfunction, irritable bowel syndrome and pudendal nerve entrapment \nor pudendal neuralgia.\nWhat is chronic pelvic pain?\nPain is defined by the International Association for the Study of \nPain as ‘an unpleasant sensory and emotional experience associated \nwith actual or potential tissue damage [1]. Understanding the impact of \npain has to acknowledge both the stimulation of the sensory receptors \nby a harmful stimuli and other factors acting centrally and contributing \nto pain perception. Chronic pelvic pain (CPP) is regarded as a symptom \nand not a diagnosis and its definition encompasses three parameters of \nlocation, severity and duration. It is most commonly defined as pain \nlocated in the lower abdominal or pelvic cavity or buttocks which \ncan be continuous or intermittent, cyclical or non-cyclical in nature. \nIt imposes functional limitation in activities of daily living (ADLs), \nleading to poorer quality of life [2] (severity). The pain must have been \npersistent for at least 6 months [3] (duration). \nThe pelvis is a complex region of the body and its geography and \ncomplicated neuroanatomy makes diagnosis of pain in the region \nextremely challenging. There is a very heavy economic and social \nimplication for patients living with chronic pelvic pain. Hence, it \nis of paramount importance that accurate diagnosis and effective \nmanagement of this condition be implemented very early in the \npresentation. CPP is of multi-source origin which makes it difficult in \nformulating a plan of care for patients with this condition. If one source \nof the pain is detected, it is important to rule out other conditions that \nmay also be contributing. For example, Howard [4] estimated that \napproximately 65% of women with endometriosis have coexistence of \ninterstitial cystitis which may account for some patients failing to have \na remission of their symptoms as only one condition is being addressed.\nHow common is this condition?\nThe estimated worldwide prevalence of CPP ranges from 2.1–24%  \n[1]. It is more prevalent in females and its prevalence in women of \nreproductive age in the USA and the UK has been reported as 14.7% \nand 24% respectively [5,6]. The direct costs of CPP has been estimated \nto be as high as $2.8 billion [4,5]. In gynaecology, endometriosis is \nperceived by many to be the main source of CPP and it has been cited \nas being the cause of CPP in 30-87% of patients [7].\nWhat are the possible causes of chronic pelvic pain?\nThe aetiology of CPP is multifactorial and incompletely understood \nand it can arise from pathologies involving various organ systems [8] \n(Figure 1). Pain disorders may coexist with CPP and intensify the \noverall pain symptoms via mechanisms of cross-organ sensitisation, \nleading to viscero-visceral or viscerosomatic hyperalgesia [9]. The \ncomplex innervation of the pelvis further complicates the diagnosis of \npelvic pain [1]. \nPain can generally be classified into visceral, somatic or neuropathic. \nVisceral pain originates from internal organs and is transmitted \nthrough sympathetic fibers of the autonomic nervous system. It is \nthus poorly localised, dull and aching in nature and associated with \nautonomic dysfunction (e.g. nausea, vomiting, sweating) [10]. \n\nBolaji II (2018) An odyssey through chronic pelvic pain in women\nFront Womens Healt, 2018         doi: 10.15761/FWH.1000154\n Volume 3(4): 2-9\nOn the other hand, somatic pain originates from muscles, skin, \nbones and joints and is transmitted along somatic sensory afferents. \nHence, this pain is well localised and sharp or burning in nature [2,11]. \nPain as a result of changes in the nerve itself is referred to as \n‘neuropathic pain’. This pain is characteristically, but not exclusively \nburning, aching or shooting in nature and presents as hyperaesthesia, \ndysaesthesias and allodynia [2]. It arises as a result of an injury to the \nperipheral or central somatosensory nervous system. CPP is thought \nto originate from a disease state that damages a particular organ \ngiving rise to either somatic or visceral pain, which then develops into \nneuropathic pain over time. \nIn cases where no precise pathology can be identified, CPP is \nthought to be due to abnormal pain perception in the central nervous \nsystem (CNS) in the absence of acute injury [12]. Janicki [13] proposed \nthat CPP is a form of complex regional pain syndrome (CRPS), resulting \nin hypersensitization of the CNS and hence decreased pain thresholds \nand augmented normal pain intensities [15]; such that normally non-\nnoxious stimuli (e.g. the sensation of a full bladder) would be perceived \nas painful.\nWhat is the approach to assessment and making a clinical \ndiagnosis?\nThe triad of thorough history, clinical examination and utilisation \nof laboratory and imaging studies are essential to arrive at an accurate \ndiagnosis. The signs and symptoms of CPP are very variable in terms of \nlocation and intensity. Initial assessment of women with CPP is the most \nimportant and this must be performed thoroughly and meticulously \nwithout haste. Patients must be allowed to narrate their story with \nattentiveness so as to explore their ideas about the cause of pain and \nuse the opportunity to reinforce some of their thoughts and discard \nmisconception regarding the pain. McGowan et al. [15] and Price et \nal. [16] found that patients presenting with CPP want their history to \nbe heard and validated and they want to receive individualised care to \nimprove their understanding and management of their pain.\nThe initial detail history should capture information about the \npattern of the pain, associated problems including urinary, bowel or \npsychological problems and the effect on posture and movement. One \nacronym that the authors found useful for assessment of chronic pelvic \npain and used by many healthcare professionals is SOCRATES (Table 1). \nIn history, it is critical to ask not only about pain but also to explore \nother systems including urologic, gastrointestinal, musculo-skeletal \nand reproductive systems. Although there are many contributory \nfactors but the problem of CPP must be considered as a whole by the \nphysician and their clients. A pain/menstrual chart may be helpful in \ntracking symptoms or activities associated with this pain. Where pain \nis cyclical in the absence of any other finding, a therapeutic trial of \ndown regulation may be more helpful than a diagnostic laparoscopy.\nNickel et al. [17] championed the use of UPOINT (urinary, \npsychosocial, organ-specific, infection, neurologic/systemic and muscle \ntenderness) [18] system (Table 2) to structurally classify and improve \nmanagement of patients with CPP. This enables the appropriate \ndiagnostic investigation to be carried out to identify the underlying \ncause of pain, so that more effective treatment can be recommended by \ntargeting on the particular aetiology. The UPOINT approach appears \nto be a valid initial assessment of a patient’s pain complaints [19,20] \nand more commonly used by the urologists. The full diagnostic criteria \nof different causes of CPP are explored in the differential diagnosis.\nClinically, palpation of the bladder and pelvic floor muscles are \nvery important and often ignored due to lack of training. Bladder pain \nmay be elicited in BPS/IC and there are two highly predictive physical \nexamination for pelvic floor dysfunction [21]. These are the Pelvic \nfloor muscle palpation (PMP) and the forced Flexion, Abduction, and \nExternal Rotation (fFAER) tests. They may help to identify those that \nhave musculoskeletal disorders contributing to chronic pelvic pain and \nwho would benefit from referral to a physiotherapist. \nEndometriosis-related lesions may be palpated during early part of \nmenstrual flow as the implants are most likely large and tender at this \n \nFigure 1. Aetiology of chronic pelvic pain\n\nBolaji II (2018) An odyssey through chronic pelvic pain in women\nFront Womens Healt, 2018         doi: 10.15761/FWH.1000154\n Volume 3(4): 3-9\nphase of the menstrual cycle. A common physical finding is cul-de-sac \ntenderness, with multiple tender nodules palpated along the cul-de-sac \nor uterosacral ligaments. Adnexal masses or adhesions are palpated \nbimanually, while deep infiltrated lesions involving the rectovaginal \nseptum are palpated rectovaginally.\nInvestigations vary according to history and examination findings \nas shown in Table 3. In gynaecology, diagnostic laparoscopy appears \nto be the most frequent and the best investigation for CPP [22,23]. The \nlaparoscopy must be comprehensive exploring the upper abdomen, \nchest as well as the pelvic cavities (Figure 2). However, it is important \nto bear in mind that a negative laparoscopy, (present is up to 90% of \nwomen with CPP [24] is not synonymous with no diagnosis or no \ndisease). Laparoscopy is only one of the many possible methods of \nevaluation of CPP. It has its limitations and pitfalls. More discriminative \nuse of laparoscopy based on the patient’s history, clinical examination, \nlaboratory and imaging findings might decrease the rate of negative \nlaparoscopies from 39–40% [23].\nFrequently, the diagnosis of CPP is assigned to a painful condition \ndependent on the initial specialist who evaluated the patient, i.e. \ngynaecologists assign gynaecologic diagnoses, whereas urologists \nassign urologic diagnoses. It is prudent for clinicians from all specialties \nto assess the multiple aetiologies that are possible in causing CPP. \nWhat are the common causes of chronic pelvic pain?\nIn gynaecological population, the five prevalent conditions \nencountered in patients with chronic pelvic pain include endometriosis, \nbladder pain syndrome/interstitial cystitis (BPS/IC), irritable bowel \nsyndrome (IBS), pelvic floor dysfunction (PFD) and pudendal nerve \nentrapment (PNE) (Table 4). The most unrecognised cause of CPP \nis the PNE which affects only 4% of patients with chronic pelvic \npain. Pelvic congestion syndrome refers to a condition in which \ncharacteristic symptoms of shifting location of pain, deep dyspareunia, \npost-coital pain, and exacerbation of pain after prolonged standing \nare associated with radiological findings of pelvic varicosities (dilated \nuterine and ovarian veins) that display reduced blood flow [25]. The \nexistence of pelvic venous congestion as a cause of chronic pelvic \npain remains controversial. A recent systematic review of diagnosis \nand management of this condition found no valid diagnostic tests, \nalthough ovarian suppression was effective in treating pelvic pain \nsymptoms. Pelvic inflammatory disease (PID) is a common cause of \nCPP in settings with a high prevalence of sexually transmitted disease. \nHowever, the underlying reason that PID often leads to CPP has not \nbeen clearly established. In one study of 780 predominantly black urban \nwomen with recently diagnosed PID, those most likely to develop CPP \nwere smokers, women with a history of two or more episodes of PID, \nand women with a low composite mental health score on standardized \ntests [26].\nEndometriosis\nEndometriosis refers to ectopic implantation and growth of \nendometrial mucosa, glands and stroma, commonly involving the \novaries, uterosacral ligaments, Pouch of Douglas and uterovescial \nperitoneum [27,28]. Since these extrauterine implants are under \ncyclic influence of ovarian hormones, they grow and break down \nwith each menstrual cycle. The symptoms of endometriosis vary in \ntheir presentation and severity; however, the commonest symptom is \npremenstrual pelvic pain and dyspareunia [29-61]. The pain usually \nbegins one or two days before expected menstruation, and it may be \nunilateral or bilateral, and lasts until the end of menses. However, some \nwomen may experience a constant, debilitating pain that interferes \nwith functional activities of daily living. Curiously, the severity of pain \ndoes not correlate well with severity of the condition and, therefore, \nsevere disease may go undiagnosed [30].\nThis pain can be attributable to several factors, namely inflammation \nsecondary to cyclic slough of endometrial glands; release of neurokinins \nand adhesions causing pressure and traction on surrounding tissues \n[61]. However, it is important to note that endometriotic pain has little \ncorrelation with the location and extent of disease, in other words, \nsome patients with endometriosis may be completely asymptomatic \n[60,61]. If the bladder is involved, patients may also complain of \ndysuria, hematuria and urinary frequency [31].\nThe pathophysiology of endometriosis remains unknown. Although \nmany theories have been proposed, the most accepted theories include \nretrograde menstruation (Sampson’s theory), coelomic metaplasia, \nvascular and lymphatic spread and altered immunosurveillance.\nEndometriosis is clinically graded into four stages of advancement \naccording to the American Society of Reproductive Medicine \nclassification (ASRM) [32] to assist with diagnosis, prognosis, \ntreatment, subsequent progress and communication among medical \nprofessionals. They are Stage I (minimal), Stage II (mild), Stage \nIII (moderate) and Stage IV (severe). Staging is based on the extent \nS Site Where is the pain? Chest, abdomen, head, pelvis, etc. Is there \na pattern of involvement?\nO Onset\nWhen did it start? How did it start? What started it? Was it \na sudden onset or more gradual? Has there been any change \nover time?\nC Character\nWhat does pain feel like now?\n     Type of pain - burning, shooting, stabbing, crushing, dull\n     Pattern of pain - colicky, constant\nR Radiation Where does it move to? Into back, arm, down a leg, etc.\nA Associations\nAre any other signs or symptoms associated with pain? E.g. is \nthere any neurological deficit (e.g. numbness where the pain \nis felt?)  Does it cause nausea, light-headedness, inability to \nlie flat, etc\nT Timing\nTime course – does the pain follow any pattern? Is the pain \nworse at any time of the day? Is the pain associated with any \nparticular activities, e.g. movement, urination, eating, passing \nstool, coughing, is It constant / intermittent, how long does it \nlast when it’s there?\nE Exacerbating / \nrelieving factors\nWhat makes it better or worse? does anything change the \npain?\nS Severity\nHow bad is it now? \n-  Pain intensity: none, mild, moderate or severe; rank on a \nscale of 1-10 scale\n- Any interference with sleep or usual activities\n- Pain relief: none, slight, moderate, good or complete\nTable 1. Socrates\nUrinary A post-void residual measured by ultrasound\nPsychosocial Ask about clinical depression and catastrophizing \n(helplessness, hopelessness)\nOrgan specific Pain improvement with bladder emptying and tenderness\nInfection Culture for myocoplasma and ureasplasma, urine culture\nNeurologic/Systemic Ask about pain outside the pelvic and diagnosis of other pain \nsyndromes\nTenderness Palpate the abdominal and pelvic skeletal muscles (via rectum \nor vagina) and check for spasm and trigger points\nAdditional tests Female Urologic Pelvic Pain Index \nTable 2. UPOINT system for Clinical Phenotyping of Chronic Pelvic Pain: minimum \ninvestigations recommended [19]\n\nBolaji II (2018) An odyssey through chronic pelvic pain in women\nFront Womens Healt, 2018         doi: 10.15761/FWH.1000154\n Volume 3(4): 4-9\nA\nB\nC\nFigure 2A. Normal looking perihepatic space. 2B) Type 1 Fitz-Hugh Curtis syndrome. 2C) Chronic PID with hydrosalpinx.\nBPS/IC IBS PFD PNE Endometriosis\nPain Pain worsens as bladder fills and \nimproves after voiding\nRome criteria:\n-Continuous/recurrent abdominal \npain, relieved with defaecation/ \nassociated with change in frequency/\nconsistency of stool\n-+/- disturbed defaecation (2 or \nmore of: altered stool frequency/ \nconsistency/ passage of stools \n(straining/ urgency/tenesmus)/ \npassage of mucus\n-Usually with bloating\nExclude red flag symptoms: \n(significant weight loss, nocturnal \nsymptoms, bloody diarrhoea, family \nhistory of colon cancer, new onset of \nsymptoms in patients >50 years)\nMore commonly suffers from \nconcomitant chronic fatigue \nsyndrome, fibromyalgia, depression, \nanxiety\nWell-localised, aching \nand deep in nature,\nfocal point tenderness\nAssociated with obesity, \nmenopause, pregnancy, \nchildbirth and inherited \ncollagen deficiency \nPain is positional \n(worsened by sitting, \nrelieved by standing, \nabsent when recumbent\nMore common in \ncompetitive cyclists, after \npregnancy, trauma, surgery \ndue to scarring\nPerimenstrual lower \nabdominal pain\nAssociated \nsymptoms\nUrgency, hesitancy, frequency, \ndyspaurenia (Pelvic Pain and Urgency/\nFrequency (PUF) patient symptom \nscale to act as a screening test for IC)\nPseudo-weakness of the \ninvolved muscles and \nreduced range of motion\nGenital numbness, urinary/\nfaecal incontinence\ndyspareunia \ndysuria, haematuria, urinary \nfrequency (if bladder \ninvolvement)\nSigns Tenderness at bladder base Normal examination\nLevator muscle spasm, \nmyofascial pain elicited \nby pelvic floor muscle \npalpation (PMP) and the \nforced flexion, abduction \nand external rotation test \n(fFAER)\nPalpation of the ischial \nspine may produce pain\ntender retroverted uterus, \ntender nodules and masses \nin pelvis, implants in \nuterosacral ligaments\nInvestigations\n24 hr voiding diary, To detect infection/\nhaematuria: Urinalysis, urine culture\nTo exclude bladder cancer or carcinoma \nin situ: urine cytology \nTo establish diagnosis:\nCystoscopy with hydrodistention of \nbladder \nIntravesical anaesthetic challenge \nDiagnosis of exclusion, \n(investigations to rule out organic \ncauses e.g. lactose intolerance \n(Hydrogen breath test), coeliac \ndisease (coeliac serology), small \nbowel bacterial overgrowth (stool \nmicroscopy+ culture), colorectal \ncancer: colonoscopy + biopsy for \npatients over 50 years or <50 with \nred flag symptoms)\n--\nEMG: to measure \nmotor latency along the \npudendal nerve (a greater \nthan normal conduction \ndelay indicates nerve \nentrapment)\nMR neurography: \nasymmetrical swelling \nand hyperintensity in \nthe affected pudendal \nneurovascular bundle\nLaparoscopy +biopsy for \nvisualisation of lesions + \nhistological confirmation \n(false +: endosalpingiosis, \nmalignancies, carbon \ndeposits from previous \nablations)\nTreatment Table 4\nDietary modification (high-fibre diet, \nincrease fluid intake)\nPsychotherapy (CBT, stress \nmanagement)\nAntispasmodics\nTricyclics or SSRI\nPhysiotherapy e.g. \nPelvic floor exercise, \nmuscle relaxants,\nelectrical stimulation to \nincrease muscle tone, \nbiofeedback\nBehavioral modification, \nphysical therapy \n(stretching exercises), \nanalgesics, medication \nfor neuropathic pain \n(gabapentin, amitriptyline), \npudendal nerve block, \nsurgical decompression, \npulsed radiofrequency\nMedications: Analgesics: \nNSAID\nHRT (COCP), progestins \nDanazol,\nGnRH\nSurgery: laparoscopy + \nablation of endometriosis or \nhysterectomy with bilateral \nsalpingo-oorphorectmy\nTable 3. Summary of findings in history (pain characteristics, associated symptoms), examination, investigation and treatment for five common aetiologies of chronic pelvic pain\nCBT: Cognitive behavioural therapy is a talking therapy that can help patient to manage their problems by changing the way they think and behave, COCP: combined oral contraceptive \npills, EMG: electromyography, GnRH: gonadotropin-releasing agonist, IBS: irritable bowel syndrome, IC: interstitial cystitis, MPS: Myofascial pain syndrome, NSAID: nonsteroidal anti-\ninflammatory agents, PFD: Pelvic floor dysfunction, PNE: pudendal nerve entrapment, PUF: Pelvic Pain and Urinary/Frequency patient symptom scale. \n\nBolaji II (2018) An odyssey through chronic pelvic pain in women\nFront Womens Healt, 2018         doi: 10.15761/FWH.1000154\n Volume 3(4): 5-9\nof the spread of lesions, density of pelvic adhesions, involvement of \npelvic organs and degree of fallopian tube occlusion. It’s important to \nremember that the stage of endometriosis is not reflective of degree of \npain, risk of infertility or predictive of the patient’s ability to conceive \nafter therapy.\nOn examination, tender nodules and masses in the pelvis, a \ntender, retroverted, fixed uterus or implants in the POD or uterosacral \nligaments are suggestive of endometriosis. The gold standard diagnostic \ninvestigation for endometriosis is laparoscopy with confirmation by \nbiopsy [60,61]. However, false positives can occur with malignancies, \nendosalpingiosis, carbon deposits from previous ablations and even \nwith normal peritoneum. Walter et al. [33] investigated the accuracy \nof solely using laparoscopic visualization in diagnosing endometriosis \nand found that only 67 out of 138 (49%) sites visually positive were also \nhistologically positive.\nManagement options include medical, surgical or a combination \nof both (Table 3), depending on the patient’s age and their desire for \nfertility augmentation and pain relief and also the stage of disease. \nMild, premenstrual endometriotic pain responds well to non-steroidal \nanti-inflammatories (NSAIDs) [34]. Hormonal therapy suppresses \noestrogen production and promotes atrophy of endometrial tissue \nimplants. Low dose, continuous, monophasic combined oral \ncontraceptives (COC) is the first-line hormonal therapy [67]. \nProgestins (e.g. medroxyprogesterone acetate, norethindrone acetate), \ngonadotropin-releasing (GnRH) agonists (e.g. goserelin, leuprolide) \nand danazol are alternative hormonal therapies [67]. GnRH agonists \nand COCs have been shown to be beneficial for patients with IBS, BPS/\nIC and pain disorders associated with perimenstrual flare-ups [35]. \nInterestingly, a phase II randomised controlled trial in Brazil showed \nthat oral therapy with melatonin 10mg/d was more effective than \nplacebo in improving daily pain, dysmenorrhea, dysuria, dyschezia \nand sleep in women with biopsy-proven endometriosis and CPP [36]. \nSurgery may be considered in older patients or those who \nsuffers from moderate or severe endometriosis unresponsive to \npharmacologic treatment. Conservative surgery eradicates visual signs \nof endometriosis and adhesions. Residual microscopic implants which \ncannot be surgically removed contribute to symptom recurrence and \ndisease progression. For women with severe persistent endometriosis, \nmore invasive surgeries may be considered e.g. hysterectomy with \nbilateral salpingo-oophorectomy. Patients who undergo a bilateral \noophorectomy should be treated with hormone replacement therapy \nas the benefits outweigh the risk of endometriosis recurrence (ASRM).\nThe recurrence rate of endometriotic lesions after five years is 19% \nwith laparoscopic removal of lesions and 10% with hysterectomy and \nbilateral oophorectomy, this is compared with 53.4% with medical \ntreatment (ASRM). However, this doesn’t reflect the recurrence rate of \npain as many women have a recurrence of pelvic pain [37]. \nIrritable bowel syndrome (IBS)\nIBS is the commonest bowel disorder, affecting over 10% of the \npopulation and it is 3 times more prevalent in women than men, mostly \naffecting women aged between 15 and 45. Although IBS is a chronic \nproblem, it is however a benign disorder, and does not progress to, or \nincrease the risk of any other disease. It has no known cure yet and its \ntreatment remains symptomatic relief.\nAlthough the underlying pathophysiology remains unclear, \nemerging literature suggests that IBS arises as a result of intestinal \ninflammation which emerges from hyper-responsiveness of the \nneuronal, immune and endocrine signalling pathways within the \nintestines, the peripheral and the central nervous system [38]. \nConsequently, the hypersensitive bowel muscles go into spasm, causing \npain. Certain foods may trigger an attack. Stressful life events are \nreported by up to 60% of IBS patients, which can exacerbate symptoms.\nThe cardinal symptoms of IBS consist of a triad of abdominal pain, \nabdominal bloating and a change in bowel habit [39] and attempts to \nrefine this clinical approach into guidelines have resulted in several \ndiagnostic criteria being created including the Manning criteria and \nRome I-III criteria. The Rome criteria, initially introduced in 1988 and \nsubsequently modified twice to yield the Rome III criteria, have become \nthe research-standard definition of constipation and IBS [40]. The \nRome III criteria for the diagnosis of irritable bowel syndrome  require \nthat patients have had recurrent abdominal pain or discomfort at least 3 \ndays per month over the last 3 months that is associated with 2 or more \nof the following: improvement with defecation, change in frequency of \nevacuations and variations in the form (appearance) of stool (criteria) \n[42]. The NICE guidelines however recommend assessment of IBS in \npatients with symptom lasting longer than six months [41].\nThe Roman criteria have proved useful for research purposes by \nensuring homogeneity of patient populations, but their applicability in \nclinical practice is extremely limited and they are seldom used [42]. The \ndiagnosis of IBS is usually made more often intuitively with remarkable \nreliability and safety.\nIBS often exhibits the following subgroups: Constipation \npredominant IBS, which is more prevalent in females and is \ncharacterised by alternating hard (> 25%) and soft stools (< 25%); \ndiarrhoea predominant IBS, which is more common in males and is \ncharacterised by alternating loose (> 25%) and hardened stools (< 25%) \nand IBS with mixed habits [39] .\nMost gynaecologists have difficulty recognising bowel symptoms \nand, therefore, do not establish a diagnosis of IBS [43-45]. The difficulty \nof the diagnosis is further increased by the fact that symptoms of IBS are \nbased on subjective accounts of patients and lack organic explanations.\nThe treatment of first choice is usually a dietary modification \nby increasing fibre and fluid intake. Drug therapy is not usually \nrecommended for the routine treatment of IBS. However, \nantispasmodics, tricyclics or selective serotonin reuptake inhibitors \n(SSRI) might be beneficial. Psychotherapy including cognitive \nbehavioural therapy (CBT) and stress management might also be \nhelpful in controlling symptoms (Table 3).\nBladder pain syndrome\nFormally referred to as interstitial cystitis, the nomenclature \nfor this condition has changed several times. There is currently no \nconsensus regarding the nomenclature and sometimes both titles have \nbeen combined as BPS/IC. BPS is the most widely used term in the \nUK and Europe whilst BPS/IC is the preferred term by the American \nAssociation of Urologist (AUA). The prevalence in the female \npopulation in the United States ranged from 3–6% [46]. \nEndometriosis\nIrritable Bowel Syndrome\nBladder Pain Syndrome/Interstitial Cystitis (BPS/IC)\nPelvic Floor Dysfunction \nPudendal Nerve Entrapment\nTable 4. The evil quintuplet\n\nBolaji II (2018) An odyssey through chronic pelvic pain in women\nFront Womens Healt, 2018         doi: 10.15761/FWH.1000154\n Volume 3(4): 6-9\nBPS is defined as “an unpleasant sensation (pain, pressure, \ndiscomfort) perceived to be related to the urinary bladder” that is \nassociated with urinary symptoms, in the absence of infection or \nother identifiable causes [47]. BPS/IC was defined by the International \nContinence Society in 2002 as suprapubic pain related to bladder \nfilling after exclusion of a urinary tract infection, along with 1 or 2 of \nincreased daytime frequency and or increased night time frequency \n[48]. The classic features include urinary urgency and frequency, \nnocturia, dyspareunia and pelvic or lower abdominal pain [49].\nThe European Society for the Study of Interstitial Cystitis (ESSIC) \nproposed the term BPS to be used in parallel with or instead of IC in \naccordance to the following criteria [50]: chronic pelvic pain lasting > \n6 months, pressure or discomfort perceived to be related to the urinary \nbladder and accompanied by at least one other urinary symptom like \nurinary urgency or frequency.\nThe aetiology of BPS/IC is still undetermined but possible causes \ninclude infection, toxins, bladder wall defects, pelvic floor dysfunction \nand autoimmune disorders [51]. The most likely primary cause seems \nto be a defective urothelium or glycosaminoglycan (GAG) layer [52]. \nClinical BPS/IC, according to Keay et al. [53] is initiated by exposure to \nnoxious stimuli causing injury to the bladder or epithelium, commonly \nfollowing an episode of bacterial cystitis, pelvic surgery, childbirth \nor urologic instrumentation. In contrast to the healthy population, \nnormal uroepithelial repair in BPS/IC patients is retarded or prevented \nas a result of elevated anti-proliferative factor and diminished epithelial \ngrowth factors [54]. Over time, the GAG layer becomes defective \nand urinary metabolities e.g. potassium ions (K+) leak through the \nbladder wall into the submucosal space, triggering an inflammatory \nreaction marked by proliferation and activation of submucosal mast \ncells [55]. Penetration of urinary constituents into the bladder wall \ncauses C-fiber activation, mast cell activation, and histamine release. \nThe resulting smooth muscle contraction, neurogenic inflammation, \nand hypersensitivity translate into the urinary urgency and frequency \nand chronic pelvic pain that are characteristic symptoms of several \nchronic bladder conditions. Mast cell degranulation not only releases \nhistamine and other inflammatory mediators, eliciting local tissue \ndamage and vasoconstriction [56], but also stimulates neurogenic \ninflammation [57] by activating capsacin-sensitive nerve fibers and \nreleasing neuropeptides such as substance P which leads to further \ninjury and fibrotic changes within the bladder. If left untreated, the \nbladder will shrink in size, compromising its functional capacity. \nChronic inflammation fuels neural up-regulation and neural changes \nwithin the spinal cord which ultimately develops into neuropathic \npain, manifesting as allodynia and hyperalgesia of the bladder and \nadjacent pelvic organs [58]. This up-regulation explains the reason for \npatients with chronic BPS/IC to have persistent vaginal or pelvic pain \neven after cystectomy.\nWithout a thorough investigation, BPS/IC can be easily \nmisdiagnosed as vaginitis, vulvodynia or pelvic floor dysfunction \nin female patients. The diagnosis of BPS/IC can be confirmed \nvia cystoscopy, with or without biopsy and hydrodistention. On \ncystoscopy, Hunter’s ulcers may be present in 10% of patients [39]. \nHydrodistention may reveal petechial haemorrhages (glomerulations) \nin symptomatic patients which are indicative of disease state [59]. \nHistological examination may show signs of neurogenic inflammation, \nevidenced by marked oedema and injury to nervous tissues and blood \nvessels in the muscularis layer [39].\nThere are a large number of therapies available to treat BPS/IC. \nThe majority of patients respond well to a multidisciplinary approach \nconsisting of dietary modification, behavioural modification and other \nmedical interventions (Figure 3, Table 5).\nPelvic floor dysfunction\nPelvic floor dysfunction is a well-known musculoskeletal cause of \nCPP. It occurs when pelvic floor muscles are either too weak or too \ntight. The major contributing factors include obesity, menopause, \npregnancy and childbirth. Some women are more likely to developing \npelvic floor dysfunction as a result of an inherited collagen deficiency. \nKeane et al. [60] found that women with congenitally weak connective \ntissue and fascia are at risk of stress urinary incontinence and pelvic \norgan prolapse. \nPelvic floor muscle palpation (PMP) is a useful physical examination \ntechnique to determine whether CPP is of musculoskeletal origin. The \ntest is considered to be positive if firm transvaginal digital palpation \nof the right and left pelvic floor muscles elicits pain [61]. The forced \nFlexion, Abduction and External Rotation test (fFAER) is considered \nto be positive when pain is elicited by flexion, abduction and external \nrotation of either leg from the supine position [49]. The presence \nof both findings correctly identifies patients with musculoskeletal \ndisorders contributing to CPP in 85% of the time while the absence of \nboth findings has 100% specificity [49]. Physiotherapy is typically \nbeneficial in relieving symptoms of the musculoskeletal origin \n(Table 3). \nPudendal nerve entrapment \nPudendal nerve entrapment or pudendal neuralgia is a disabling \nform of genital pain resulting from inflammation, compression or \nentrapment of the pudendal nerve (S2,3,4), affecting 4% of patients \npresenting with CPP. It has been associated with childbirth, pelvic \nsurgery, intense cycling, sacroiliac skeletal abnormalities or age-related \nchanges. Post-menopausal women have especially high risks since \npudendal neuralgia has been shown to be related to urogenital atrophy \nas a result of decreased oestrogen level and hence collagen support as \nwomen age [62]. \nClinical features include pelvic pain with sitting which worsens \nthroughout the day and decreases with standing or lying down. This \ncondition is thus very common in current society since many people \nhave office jobs and make frequent, long journeys [63]. Similar to other \ncauses, pudendal neuralgia is also associated with sexual dysfunction \nand difficulty in urination and defaecation, consequently, the diagnosis \nis often difficult to manage with a reported delay ranging from 2 to 10 years \n[64]. There are 5 essential diagnostic criteria (Nantes criteria) [65] that are \nrecommended for the diagnosis of pudendal neuropathy (Table 6).\nThere must be no symptoms of exclusion criteria. Patients with \nsolely coccygeal, gluteal or hypogastric pain with imaging abnormalities \nthat may explain the symptoms generally do not have pudendal \nneuralgia. The diagnosis should be confirmed with electrophysiological \nand imaging studies such as colour duplex scanning and magnetic \nresonance neurography. Electromyography with a greater than normal \nconduction delay may suggest pudendal nerve entrapment in Alcock’s \ncanal.\nPudendal neuralgia can be managed with either conservative \nor surgical approaches (Table 3). Conservative treatment includes \nbehavioural modifications, pelvic floor physiotherapy, analgesics, \npudendal nerve block (transacral block at S2-S4) and botox injections \n(in case of muscle spasms) [66-68]. In case of failed conservative \ntreatment, surgical decompression via the transperineal, transgluteal \n\nBolaji II (2018) An odyssey through chronic pelvic pain in women\nFront Womens Healt, 2018         doi: 10.15761/FWH.1000154\n Volume 3(4): 7-9\nPentosan \npolysulfate Antihistamines Antidepressants Neuroleptics Supplementary oral \ntherapy Intravesical therapy\nMechanism\nof action\nRe-establish \nendothelial lining \n[71]\nMast cell stabiliser\nModify pain, improves \ninsomnia, anticholinergic \neffect\nDecrease neurogenic \ninflammation\nDecrease bladder \ndiscomfort\nDecrease bladder discomfort, \ncontrol bladder spasm\nExample -\nHydroxyzine [72] \n(sedating)\nCetirizine [73]\n(non-sedating)\nTricyclics – amitriptyline, \ntrazodone, doxepin, \nnortriptyline\nSSRI – paroxetine, \nfluoxetine, citalopram, \nvenlafaxine, sertraline\nGabapentin, phenytoin, \ncarbamazepine, \nvalproate\nUrinary analgesics, \nantiseptics, alkalizers, e.g. \nPhenazopyridine, Uromax, \nUrised\nFDA approved: -Dimethyl \nsulfoxide (DMSO); [74]\n-Oxybutynin (5-10 mg \ncrushed and suspended in \n10cc of water);\n-Pentosan polysulfate/ heparin \n(daily) [75]\nNon-FDA approved:\n-Hyaluronidase [76]\n-Bacillus Calmette-Guérin \n(BCG) [77]\nDose 100-300 mg 25-75 mg 25-100 mg 100-800 mg\n-\n50cc\nRoute Oral Oral Oral Oral catheterisation\nFrequency 3 times/day Once at night Once at night 3 times/day Once/week for > 6 weeks\nSide effects Headache, alopecia, \nGI upset\nVisual disturbance, low \nblood pressure, GI upset Sympathomimetic effect Sedation, liver \nimpairment Bladder irritation\nOthers\nFull effect may not be \nseen for 6-9 months.\nCompliance is \nnecessary as \nbenefit of therapy \nis dependent on \nlength of time under \ntreatment.\nIn spring and fall, when \nmany IC patients suffer \nfrom seasonal allergies, an \nadditional 10-25 mg every \n6 hours may be required.\nImipramine should be \navoided as this agent \nexacerbates dysfunctional \nvoiding.\nFor patients who fail to \nrespond to oral therapy\nTable 5. Treatment of painful bladder syndrome/ interstitial cystitis (pbs/ic)\nGI: gastrointestinal\nSSRI: Selective Serotonin Re-uptake Inhibitors\nDose, frequency, route stated in the table is of the underlined drug.\n \n \n \n \n \n \n \n \n \n  \n \n \n \n \nKey: \n Factors predisposing to bladder injury \n \nPathological mechanism of interstitial cystitis \n \n Mechanism of action of pharmacological agents for interstitial cystitis \n  \n Mode of conservative and medical treatment of interstitial cystitis \n‘+’         Stimulates \n‘-‘  Inhibits \n \n \n \n \nFigure 3. Multifactorial aetiology of Bladder pain syndrome/Interstitial cystitis (BPS/IC) and the role of multimodality therapy. \n*Bladder pain Syndrome/Interstitial cystitis (BPS/IC) diet involves avoidance of coffee, tea, soda, alcohol, citrus juices, and cranberry juice, foods and beverages containing artificial \nsweeteners, hot peppers and spicy foods, which may exacerbate BPS/IC.\n\nBolaji II (2018) An odyssey through chronic pelvic pain in women\nFront Womens Healt, 2018         doi: 10.15761/FWH.1000154\n Volume 3(4): 8-9\nor transischiorectal approach), computed tomography-guided pulse-\ndose radiofrequency of the pudendal nerve or spinal cord stimulation \nof the monus medullaris may be considered [54,69,70].\nConclusion\nWhen approaching a patient with chronic pelvic pain, it is \nimportant to consider interstitial cystitis, irritable bowel syndrome, \npelvic floor dysfunction, pudendal neuralgia and endometriosis \nas differential diagnoses. CPP should be managed using a multi-\ndisciplinary and multimodal approach comprising medical, surgical \nand adjuvant therapies. Currently, clinical practice regarding CPP is \nstill not sufficiently evidence-based. Given the significant emotional, \nphysical and healthcare costs associated with CPP, there is a vital need \nfor well-controlled randomized clinical trials to be performed. All \nphysicians treating patients with pelvic pain have to be aware of all the \npotential causes of pelvic pain to ensure adequate and holistic approach \nto treatment. Addressing only the commonest cause will not lead to \nlong lasting remission.\nDeclaration of interest statement\nWe have read the JMIG policy on declaration of interests and \ndeclared that we have no declarations of interest.\nContributorship statement\nIIB planned the organisation, content and structure of the article. \nSS performed the literature review and drafted the article with crucial \nadditions and edition from IIB. 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