{"paper_id":"b75b3a66-ffbc-4376-b459-7462b123b643","body_text":"1 \nManagement of chronic primary pelvic \npain syndromes \n \n \n \nBrian A. Parsons1, Andrew P. Baranowski2, Bary Berghmans3, Jan Borovicka4, Angela \nM. Cottrell5, P. Dinis-Oliveira6, Sohier Elneil7, John Hughes8, Bert E.J. Messelink9, \nAmanda C. de C Williams10, Pedro Abreu-Mendes6, Valentin Zumstein11, Daniel S. \nEngeler11 \n \n \n \nAffiliations: \n \n1. Royal Devon and Exeter Hospital, Exeter, UK \n2. University College London and the National Hospital for Neurology and Neurosurgery, University \nCollege London Hospitals Foundation Trust, London, UK \n3. Pelvic Care Centre Maastricht, Maastricht University Medical Centre, Maastricht, The \nNetherlands \n4. Department of Gastroenterology/Hepatology, Cantonal Hospital of St. Gallen, School of \nMedicine, University of St. Gallen, St. Gallen, Switzerland \n5. East of England Deanery, London, UK \n6. Department of Urology, Hospital de Sao Joao, University of Porto Faculty of Medicine, Porto, \nPortugal \n7. University College Hospital and the Hospital for Neurology and Neurosurgery, London, UK \n8. The James Cook University Hospital, Middlesbrough, UK \n9. Department of Urology, Medical Centre Leeuwarden, Leeuwarden, The Netherlands \n10. Research Department of Clinical, Educational & Health Psychology, University College London, \nLondon, UK \n11. Department of Urology, Cantonal Hospital of St. Gallen, School of Medicine, University of St. \nGallen, St. Gallen, Switzerland \n \n \n \n \n \n \n \n\n \n2 \nAbstract \n \nManagement of chronic pelvic pain remains a huge challenge for care providers and a major burden for health \ncare systems. Treating chronic pain that has no obvious cause warrants an understanding of the difficulties in \nmanaging these conditions. Chronic pain has been recently accepted as a disease in its own right by the World \nHealth Organisation (WHO), with chronic pain without obvious cause being classified as chronic primary pain. \nDespite innumerable treatments that have been proposed and tried so far for chronic pelvic pain, unimodal \ntherapeutic options are mostly unsuccessful, especially in non-selected individuals. In contrast, individualised \nmultimodal management of chronic pelvic pain seems to be most promising approach and may lead to an \nacceptable situation for a large proportion of patients. In this review, the interdisciplinary and \ninterprofessional European Association of Urology (EAU) Chronic Pelvic Pain Guideline Group gives a \ncontemporary overview on the most important concepts to successfully diagnose and treat this challenging \ndisease entity. \n \nIntroduction  \n \nChronic pain syndromes are highly prevalent with significant negative impact on the quality of life (QoL) of \naffected individuals [1]. This article provides an overview of the aetiology, classification, diagnosis and \nmanagement of patients with chronic pelvic pain syndromes for urologists caring for such patients. The \nevidence underpinning this review has been gathered through systematic literature searches performed by \nthe European Association of Urology (EAU) Chronic Pelvic Pain Guideline Group with regular updates to \nincorporate the latest available evidence into clinical practice. [2]. For more detailed information, the 2021 \nEAU Guidelines on Chronic Pelvic Pain is available in print and online [2].  \n \nDefinitions and terminology \n \nPain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue \ndamage, or described in terms of such damage (International Association for the Study of Pain Taxonomy). \nChronic pain refers to pain lasting more than three months. Now included in the 11th revision of the World \nHealth Organisation International Classification of Diseases (ICD-11). In ICD-11, the term chronic primary pain \nrefers to pain that has no clear underlying cause and chronic secondary pain is used for pain associated with \nanother diagnosis or recognised pathology. Chronic pelvic pain (CPP) refers to persistent continuous or \nrecurrent pain perceived in structures related to male or female pelvis for at least three months, but a longer \nperiod of more than 6 months may be appropriate for cyclical pain.  \n \nAetiology and pathophysiology \n \nPeripheral and central mechanisms \nAnimal and clinical research have indicated that many underlying chronic pain mechanisms are centrally \nmediated with central sensitisation and neural pathway modulation maintaining pain perception in the \nabsence of an on-going peripheral trigger or pathology [3]. Perception of a painful stimulus (nociception) \nrequires transmission of information to higher centres and activated pain pathways are modulated at the \nspinal cord level by a number of pathways ascending and decending. Peripherally, acute pain mechanisms can \nlead to sensitisation of nociceptive transducers and activation of silent afferents that increase afferent \n\n \n3 \nsignalling and maintain pain. Central sensitisation [4] is responsible for a decrease in response threshold and \nan increase in the magnitude and duration of dorsal horn neuron response. Increased signalling to the central \nnervous system (CNS) amplifies what is perceived from a peripheral stimulus (hyperaesthesia) so that non-\npainful stimuli are perceived as painful (allodynia) and noxious stimuli are magnified with an increased level \nof pain (hyperalgesia). In visceral hyperalgesia, sub-threshold non-perceptible visceral stimuli are perceived \nresulting in painful sensations such as a feeling of fullness or a need to void/defecate. Convergence of afferents \nfrom visceral and somatic sites onto the same second order projection neurons may result in pain being \nperceived at a different location to its site of origin (referred pain) as higher centres fail to distinguish the \nsource of the nociceptive signal.  \n \nSensitisation of autonomic nervous system afferent fibres can cause a sensitivity to sympathetic stimulation \nand modification of the efferent output may produce end-organ dysfunction and functional abnormalities. \nSensitisation of somatic efferent pathways may explain trophic changes found in somatic tissues. Central \nmechanisms are also important in the pathogenesis of muscle hyperalgesia with muscle tenderness and trigger \npoints implicated as a source of pain. \n \nPsychological mechanisms \nPain processing is complex as nociceptive pathway activation is associated with emotional, cognitive, \nbehavioural and sexual responses that involve neural networks rather than distinct centres. Psychological \nprocesses affect supratentorial processing of pain, producing inhibition and facilitation of nociceptive signals, \ninfluencing their appraisal and interpretation and modulating the response and experience of pain. Functional \nMRI has indicated that psychological modulation of visceral pain probably involves multiple pathways that \nresult from a persistent strengthening of synapses (long-term potentiation) in response to patterns of activity \n[5]. Psychological factors are relevant to the maintenance of pelvic pain as beliefs about pain contribute to its \nexperience and symptom-related anxiety and central pain amplification may be measurably linked [6]. The \nvarious mechanisms of CNS facilitation, amplification and failure of inhibition, mean that there is no simple \nrelationship between physical findings, pain experienced and resulting distress and restriction of activities. \n \nRisk factors \nMany  factors can increase an individual’s susceptibility to developing chronic pain. Genetics play a role as \nfamily clusters of pain conditions have been reported with subtle changes in receptors and their transmitters \ndescribed. Developmental, environmental and social factors are important as twin studies have shown that \nthe impact of genetics on the variation in individual susceptibility for some pain syndromes is low [7]. The \nendocrine system is important in visceral function and stress related to significant life events may alter \ndevelopment of the hypothalamic-pituitary-adrenal axis and the chemicals released [8]. Upregulation of \ncorticotrophin-releasing hormone has been implicated in several pain states and may exert its effect by acting \non mast cells. Stress can also influence pain levels through dysregulation of serotonergic pathways and \nevidence suggests that sex hormones may modulate nociception and pain perception [9].  \n \nClassification of chronic pelvic pain syndromes \n \nCPP conditions can be subdivided into pain syndromes (chronic primary pain) that have no obvious causative \npathology  and non-pain syndromes (chronic secondary pain) that have classical well-defined aetiology (e.g. \ninfection, neoplasia). Pain syndromes are conditions in which pain is the main symptom and pain as a disease \nprocess is considered the cause.  \n \nChronic primary pelvic pain syndromes (CPPPS) are a diagnosis of exclusion and refer to the occurrence of CPP \nwhen there is no proven infection or obvious local pathology accounting for the pain. The term syndrome \nencompasses the negative emotional, cognitive, behavioural, sexual and functional consequences of chronic \npain and encourages a holistic approach to management with multidisciplinary input. In the absence of well-\n\n \n4 \ndefined aetiological mechanisms, CPPPS are classified by describing them in terms of their symptoms, signs \nand, where possible, investigations. This phenotyping has clinical and research validity and should include \ndisturbances of organ or system function caused by changes in their control mechanisms. Spurious \nterminology must be avoided, especially if it implies an unproven causality. Terms that end in “itis” should \nonly be used if infection and/or inflammation has been proven to be the cause of the pain.  \n \nPain perception in CPPPS may focus on a particular pelvic organ/structure, may affect more than one pelvic \norgan and can be associated with systemic disorders such as chronic fatigue syndrome and fibromyalgia. When \npain is localised to a single organ, some specialists use specific end-organ terms (e.g. primary bladder pain \nsyndrome). For non-specific, poorly localised pelvic pain affecting more than one organ site, the generic term \nCPPPS should be applied. Despite a general tendency to move away from end-organ nomenclature, a diagnosis \nor name ascribed to a set of symptoms can provide patients with a sense of being understood, may help with \nacceptance of the problem as chronic, resolve unfounded fears about its implications and encourage \nengagement with therapeutic endeavours and self-management. \n \nPrevalence \n \nPelvic pain syndromes increase with age but information on their true prevalence is limited by variations in \ndiagnostic criteria, evaluation tools and symptom overlap with other conditions. Using a vague definition of \ncontinuous or episodic pain situated below the umbilicus over six months, one study reported that CPP was \none of the commonest diagnoses in primary care units in Great Britain with monthly and annual prevalence \nrates of 21.5/1,000 and 38.3/1,000 respectively [10].  \n \nFunctional disturbances \n \nSexual dysfunction \nStudies of men with pelvic pain have reported higher chances of suffering from erectile and ejaculatory \ndysfunction [11]. Women with CPP have more sexual problems than patients with any other type of chronic \npain disorder with sexual avoidance, dyspareunia and “vaginismus” most commonly reported [12]. \nPsychological factors (low self-esteem, depression, anxiety), physiological factors (such as fatigue, nausea and \npain) and pain medications (opioids, selective serotonin re-uptake inhibitors) can contribute to loss of libido, \ndelay ejaculation and affect sexual function.  \n \nPelvic floor muscle dysfunction \nAn association between pelvic pain and muscular dysfunction (especially overactivity) is now recognised and \nhas been reported in patients with CPP [13, 14]. Repeated or chronic muscular overload can activate trigger \npoints within the pelvic floor and adjacent (abdominal, gluteal and iliopsoas) muscles. Trigger points are hyper-\nirritable spots within taut muscle bands that prevent full muscle lengthening and restrict range of movement. \nPain is aggravated by trigger point pressure or sustained/repeated pelvic floor muscle contraction such as pain \nrelated to voiding or defecation.  \n \n \nClinical assessment \n \nHistory \nCPPPSs are symptomatic diagnoses so history is key in evaluating patients with CPP. Specific disease-\nassociated pelvic pain must be ruled out and red flag symptoms investigated by the relevant end-organ \n\n \n5 \nspecialist. Some patients can relate pain onset to an acute event such as surgery, sepsis or trauma, but for \nmost it will be idiopathic. Burning is the commonest descriptor for neuropathic-type pain, but crushing and \nelectric are also used. Patients may report the feeling of a swelling or foreign body, such as a golf or tennis \nball, in the rectum or perineum. \n \nEnquiring about pelvic organ function is important for phenotyping a patient’s condition: lower urinary tract \nfunction and the influence of micturition on pain, anorectal function and the relationship between bowel habit \nand pain, sexual function and gynaecological symptoms. In women the temporal relation of pain to the \nmenstrual cycle may help define the aetiology. A sexual history, including previous sexually transmitted \ninfections, urethral/vaginal discharge, previous sexual trauma and a woman’s cervical smear history is \nmandatory. A full urogynaecological history is important in individuals who have had continence or prolapse \nsurgery using non-absorbable mesh. Dysfunction affecting two or more pelvic organs, should raise suspicion \nof pelvic floor muscle dysfunction or central sensitisation \n \nDetermining disease severity, its progression and treatment response requires validated symptom-scoring \ninstruments. They are recommended for basic evaluation and therapeutic monitoring of patients with CPPPS. \nWhere the primary treatment outcome is pain relief, it is useful to agree a clinically meaningful level of relief \nbefore starting treatment. The most reliable methods for assessing pain are a five point verbal scale (none, \nmild, moderate, severe, very severe pain), a visual analogue special scale or a 0-10-point numerical scale. \nGeneric QoL measures are important and the Brief Pain Inventory provides a broad assessment of the impact \nof pain on various aspects of life [15]. In males, sexual dysfunction can be evaluated using the International \nIndex of Erectile Function and Premature Ejaculation Diagnostic Tool. The Female Sexual Function Index (FSFI) \nis a brief, multi-dimensional self-report instrument developed for assessing key dimensions of sexual function \nin women including desire, subjective arousal, lubrication, orgasm, satisfaction, and pain. \n \nDirect questioning about the patient’s view of what is wrong and their concerns can be more helpful than \nanxiety questionnaires. Anxiety about pain often refers to fears about missed pathology (particularly cancer) \n[6] or uncertainties about treatment and prognosis. Depression or depressed mood are common in chronic \npain [16], often due to losses (work, leisure activities, social relationships, etc) related to chronic pain. \n \n \nPhysical evaluation \nClinical examination (with a chaperone present) helps to confirm or refute initial impressions gained from the \nhistory. Appropriate consent must be obtained including the risk of exacerbating pain during examination. \nAbdominal and pelvic examination including the external genitalia aims to exclude gross pelvic pathology and \ndemonstrate sites of tenderness. Neurological examination is considered an integral part of the assessment \nand undertaken if appropriate. Many authors recommend assessing for cutaneous allodynia along the \ndermatomes of the abdomen (T11-L1) and the perineum (S3) and recording the degree of tenderness. The \nbulbocavernosus reflex in men provides information about the intactness of the pudendal nerves. A general \nmusculoskeletal (tender point) evaluation, including muscles outside the pelvis, may help diagnose myofascial \naspects of pelvic pain [17]. \n \nWhen assessing pelvic floor muscle function, a vaginal or rectal examination should be performed according \nto the International Continence Society report [18]. An internal examination is important for diagnosing pelvic \norgan prolapse and cervical abnormalities in women. Perianal dermatitis can be a sign of faecal incontinence \nor diarrhoea and anal fissures may be overlooked. Digital rectal examination is used to assess anal sphincter \ntone, the rectum, muscle tenderness and trigger points (including puborectalis), and prostate abnormalities \nincluding pain on palpation. \n \nInvestigations \n\n \n6 \nThere is no specific diagnostic test for CPPPS. Investigations are used to identify and exclude specific diseases \nassociated with pelvic pain and for phenotypic description of pain syndromes. Investigations should be \nperformed according to appropriate guidelines to exclude diseases with known aetiologies that present with \nsymptoms identical to those of CPPPS. \n \nPhenotyping \nGiven the polysymptomatic nature of CPPPS, clinical phenotyping systems can aid and standardise assessment \nof affected individuals by setting out series of domains that should be considered. Clinical phenotyping \nsystems promote holistic patient care and potentially simplify treatment by promoting goal-directed \nmultimodal therapy. UPOINTS is a promising system despite possibly under-assessing relevant psychological \nvariables [19]. Having clear records for each system affected will significantly help support treatment. \n \nManagement \n \nThe management of CPPPS is based on a bio-psychosocial model with active patient involvement. Ensuring  \nappropriate patient information and understanding improves adherence to treatment and underpins self-\nmanagement. Single interventions rarely work in isolation and multimodal interventions addressing affected \ndomains need to be considered within a personalised management strategy. A general overview of available \ntreatment options is outlined below, with CPPPS-specific management detailed in subsequent sections. Where \nno evidence based treatments exist, CPPPS management should be underpinned by the principles that apply \nto other chronic pain disorders.  \n \nPhysical therapy \nPatients with CPP often have poor to absent pelvic floor muscle function [20] and stretching affected muscle \ngroups helps regain length and function. Pelvic floor relaxation techniques taught by specialised \nphysiotherapists can reduce pelvic floor over-activity and help interrupt the pain-spasm cycle. Myofascial \ntrigger points can be treated by manual therapy and dry or wet needling, but strong evidence for effectiveness \nof these techniques is lacking [21, 22]. Encouraging chronic primary pain sufferers to remain physically active \nhas general health benefits, but exercise has been shown to reduce pain and improve QoL especially for \nprofessionally-led supervised group exercise [23].  \n \nPsychological therapy \nEarly identification and management of psychological symptoms such depression and anxiety may ameliorate \npain and reduce distress. Psychological interventions can be directed at the pain itself to reduce its impact on \nlife or at adjustment to pain to improve mood, function and reduce healthcare use, with or without pain \nreduction [24]. A systematic review of the few heterogeneous trials of psychologically based treatment for \npelvic pain found some short-term benefits for pain comparable to that achieved by pharmacotherapy, but \nthis was not sustained at follow-up.  \n \nPharmacological treatment  \nFew studies have investigated medications used for CPPPS [25], so the evidence for pharmacotherapy is \nderived from findings for general chronic pain. If drug benefit is limited by side-effects, then dose titration is \nused to determine the lowest effective dose.  \n \nSimple analgesia \nParacetamol is an antipyretic analgesic with a central mechanism of action that is well tolerated with few side \neffects [26]. Non-steroidal anti-inflammatory agents (NSAIDs) are anti-inflammatory, antipyretic analgesics \nthat act peripherally by inhibiting the enzyme cyclooxygenase.  NSAIDs have a higher incidence of side effects \nand  evidence is lacking for their use in CPP.  \n \n\n \n7 \nNeuromodulators \nNeuromodulators are used to modulate neuropathic or centrally mediated pain. The evidence for treatment \nof CPP is lacking but is present for other painful conditions. Several classes are available but all have side-\neffects that may limit use. The UK National Institute for Health and Clinical Excellence has reviewed the \npharmacological management of neuropathic pain with recent guidance on neuromodulator use in chronic \npain [23, 27]. \n   \nDespite being an off-label indication, several antidepressants have been recommended for treating chronic \nprimary pain. Tricyclic antidepressants have anxiolytic effects with multiple mechanisms of action including \nacetylcholine receptor blockade, inhibition of serotonin and noradrenaline re-uptake, and blockade of H1 \nhistamine receptors. Amitriptyline is most commonly used with doses ranging from 10 to 150 mg/day but \nnortriptyline and imipramine are alternatives. Duloxetine is the only licensed serotonin-noradrenaline re-\nuptake inhibitor antidepressant with evidence for use in neuropathic pain. There is moderately strong \nevidence of benefit in diabetic neuropathy and fibromyalgia at a dose of 60 mg/day but side-effects often limit \nuse [28].  \n \nThe anticonvulsant carbamazepine has evidence of moderate benefit for neuropathic pain, but is no longer a \nfirst choice agent because of potentially serious side effects [29]. Other anticonvulsants include gabapentin \nand pregabalin for neuropathic pain, but the evidence for primary pelvic pains is limited with at least one \npublication suggesting gabapentin does not help. As a consequence, anticonvulsants are best administered by \npain specialists familiar with their use. \n \nOpioids \nAlthough opioids may be beneficial in chronic non-cancer pain in small numbers of patients at low doses in a \nmanaged setting, there is mounting evidence of a limited role in this population. Opioids can have harmful \neffects on the endocrine and immune systems with a growing understanding of opioid-induced hyperalgesia, \nin which patients taking opioids paradoxically, become more sensitive to painful stimuli [30]. Side-effects are \ncommon, including constipation, nausea, opioid tolerance and psychological changes, with the risk of harm \nincreasing substantially at doses above 120mg/day morphine equivalence. Opioids should be administered by \nclinicians experienced in their use with arrangements made for formal monitoring, follow-up and review. \nOpioids Aware is an excellent web-based resource for patients and health care professionals \n(https://fpm.ac.uk/opioids-aware) [30]. \n \nCannabinoids \nThe evidence base for cannabinoid use in pain is weak and well conducted trials are necessary [Moore et al., \n2021].       \n \nNerve blocks  \nNerve blocks may have a diagnostic and therapeutic role for pain management, but the evidence base for \nthese interventions for chronic non-malignant pain is weak [31]. Injection of local anaesthetic and steroid at a \nnerve injury site may produce therapeutic actions by blocking sodium channels and reducing inflammation \nand swelling. \n \nUrological pain syndromes \n \nPrimary prostate pain syndrome \nPrimary prostate pain syndrome (PPPS) refers to persistent or recurrent episodic pain (reproduced by prostate \npalpation) for a minimum of 3 months with no proven infection or obvious local pathology. The terms chronic \nprostatitis and prostadynia should be avoided. No single aetiological explanation has been identified and PPPS \nprobably develops in susceptible men exposed to unidentified initiating factors. Infection should be excluded \n\n \n8 \nwith microscopy and culture of voided urine pre- and post-prostate massage (two-glass test) being a useful \nbacterial localisation screening procedure [32]. In high risk men, PSA testing and MRI scanning may be \nconsidered after appropriate counselling. The National Institute of Health consensus classification of \nprostatitis includes infection (types I and II), which are best considered as specific disease-associated pelvic \npain [33]. The National Institute of Health Chronic Prostatitis Symptom Index is a validated symptom-scoring \ntool. \n \nPrimary bladder pain syndrome \nPrimary bladder pain syndrome (PBPS) refers to persistent or recurrent pain perceived suprapubically in the \nbladder area, accompanied by at least one other symptom, such as worsening pain with filling, transient relief \nwith voiding and daytime and/or night-time urinary frequency. Terms such as interstitial cystitis (IC) and \npainful bladder syndrome are no longer recommended. \n \nThe cause is thought to be an initial unidentified bladder insult leading to urothelial damage, neurogenic \ninflammation and pain. An infective cause has not been confirmed. Defects in the urothelial \nglycosaminoglycan layer have been implicated with a role for mast cell histamine release proposed. PBPS \nprevalence ranges from 0.06% to 30% with a female predominance (about 10:1) [34, 35] but no clear racial \ndifference [36]. There is increasing evidence that children can be affected [37]. \n \nUrinalysis and urine culture (including culture for TB if sterile pyuria) should be checked with urine cytology \nalso recommended in high risk groups. Pain in PBPS does not correlate with cystoscopic or histologic findings, \nbut these are important for diagnosis, ruling out confusable conditions and defining phenotypes. The \nEuropean Society for the Study of Interstitial Cystitis has suggested a standardised scheme of sub-\nclassifications [38] to acknowledge differences and make it easier to compare various studies. The O’Leary-\nSant Symptom Index (Interstitial Cystitis Symptom Index) is a symptom-scoring instrument validated in a large \nstudy [39]. Intravesical therapies and surgical intervention should be considered when conservative approach \nfails. Botulinum toxin application, neuromodulation and transurethral resection have been shown effective in \nsubsets of patients. \n \nPrimary scrotal pain syndrome \nPrimary scrotal pain syndrome refers to persistent or recurrent episodic pain perceived within the contents of \nthe scrotum. No specific pathology is identifiable, but an injury or intervention along the course of the \nilioinguinal, genitofemoral and pudendal nerves that innervate the scrotum can cause pain perceived in that \narea. Urinary tract and sexually transmitted infections need to be excluded. Scrotal ultrasound does not help \nin diagnosis or treatment of scrotal pain, but excludes confusable conditions. Microsurgical denervation of the \nspermatic cord can be considered in patients who have failed conservative and pharmacological treatment, \nas it can provide good long-term symptomatic relief in patients with testicular pain responding to spermatic \ncord nerve block [40]. \n \nPrimary urethral pain syndrome \nPrimary urethral pain syndrome can affect men and women and refers to chronic or recurrent episodic pain \nperceived in the urethra.  As with PBPS, epithelial damage and neuropathic hypersensitivity following urinary \ntract infection are thought to be important. There is no specific treatment, but laser therapy of the trigone \nhas been reported with good results [41].  \n \nNon-urological pain syndromes \n \nPrimary vulvar pain syndrome \nPrimary vulvar pain syndrome (PVPS) refers to pain in the vagina or female external genital organs that persists \nfor more than 3 months and can be generalised or focal. It is poorly understood and usually precedes \n\n \n9 \ndyspareunia. The terms vulvodynia and chronic vaginal pain are no longer recommended. In generalised PVPS, \npain occurs in different areas of the vulva at different times and may be constant or intermittent. Touch or \npressure does not initiate it but can exacerbate it. In focal PVPS, the pain is at the vaginal introitus and \ndescribed as a burning sensation that only develops after touch or pressure, such as during penetration. \n \nPrimary anorectal pain syndrome \nPrimary anorectal pain syndrome (PAPS) refers to continuous, recurrent or episodic pain perceived in the anal \ncanal and/or rectum in the absence of proven infection or local pathology. The Rome III criteria for functional \nanorectal pain disorders should be fulfilled for 3 months with symptom onset at least six months before \ndiagnosis [42]. Pain may be continuous (chronic proctalgia) or intermittent with episodic cramping, aching or \nstabbing pain lasting several seconds to 30 minutes with no pain between episodes (proctalgia fugax). Most \npatients with intermittent PAPS do not report it to their physicians with pain attacks occurring less than five \ntimes a year in over half of patients. Bowel dysfunction is common with excessive straining, anal digitation in \ndyssynergic (paradoxical) defecation and a sensation of anal blockage reported by some affected individuals. \nDuring examination, exquisite tenderness during posterior traction on the puborectalis muscle (“levator ani \nsyndrome”) is thought to be due to pelvic floor muscle over-activity \n \nChronic post-surgical pain \nChronic post-surgical pain (CPSP) is defined as pain that develops or increases in intensity after a surgical \nprocedure and persists beyond the healing process (more than 3 months). It has now been classified by ICD-\n11 as a chronic pain condition. Abdominopelvic operations with higher risk of CPSP include bariatric surgery, \ninguinal hernia repair, vasectomy, hysterectomy and caesarean section. \n \nPost-vasectomy scrotal pain syndrome occurs in 2-20% of men who have undergone a vasectomy [43]. \nUnderlying mechanisms are poorly understood, but the risk is significantly lower with no-scalpel technique \n[44]. Reversal of vasectomy can cure symptoms especially if patency is achieved. An RCT reported high rates \nof symptomatic improvement (80%) with pulsed radio-frequency to the ilioinguinal and genitofemoral nerves \nbut follow-up was limited to 3 months. The evidence for epididymectomy is poor and is less likely to provide \nbenefit if the epididymis has a normal sonographic appearance. \n \nPost-inguinal hernia repair pain develops in up to 10% of patients at 6 months and may present with groin or \nscrotal pain. The risk is higher following laparoscopic rather than open surgery [45]. Limited evidence from \ncase series has shown that neurectomy of damaged nerves can lead to symptomatic improvement. \n \nThe incidence of CPSP following hysterectomy is difficult to determine as pain is a common indication for the \noperation. Rates approximate 28% so careful case selection and management of patient expectation is \nimportant [46]. There is also a significant incidence of CPSP at 12 months following caesarean section so \ncareful counselling is needed in non-emergency cases . \n \nFlexible polypropylene plastic mesh implants developed and inserted to treat urinary stress incontinence and \nuterovaginal prolapse now carry a significant ‘health and safety warning ’with complication rates close to 10% \nthat include chronic pelvic pain, chronic infections, erosion into surrounding structures (vagina, bladder and \nurethra) and nerve and musculoskeletal damage [47, 48]. Mesh-related complications have a significant \nimpact on patients ’QoL so early recognition is important. Mesh removal may be necessary in difficult-to-treat \npain and should be provided within multi-disciplinary tertiary settings [49]. This is complex surgery requiring \nremoval of dense scar tissue and reconstruction of the vagina, urethra and bladder, but can have beneficial \nand durable effects on chronic pain [50].  \n \n\n \n10 \nConclusions \nCPPPSs are symptomatic diagnoses that have significant negative impact on affected individuals. Specific \ndisease-associated causes of pelvic pain need to be excluded. Phenotyping is important for diagnosis and \nprovides an approach to management of affected patients by promoting goal-directed treatment of the \nfunctional, emotional, behavioural, sexual and physical consequences. Evidence based treatments for CPPPSs \nare limited so management follows the principles used for treating other chronic pain disorders. \n \nFunding \nThis work has no special sources of funding. \n \nDisclosure of Interests \n \nDaniel Engeler has previously received honoraria from Astellas Pharma, Janssen-Cillag and Medtronic. \n \nAbbreviations \n \nCNS  Central nervous system \nCPP  Chronic Pelvic Pain \nCPPPS  Chronic primary pelvic pain syndrome \nEAU  European Association of Urology \nFSFI  Female Sexual Function Index \nICD-11  World Health Organisation International Classification of Diseases 11th Revision \nPPPS  Primary prostate pain syndrome \nPBPS  Primary bladder pain syndrome \nPVPS  Primary vulval pain syndrome \nPAPS  Primary anorectal pain syndrome \nQoL  Quality of life \nWHO  World Health Organisation \n \n\n \n11 \nReferences \n1. 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