Chronic Pelvic Pain

5. MANAGEMENT

The philosophy for the management of chronic pelvic pain is based on a bio-psychosocial model. This is a holistic approach with patients’ active involvement. Single interventions rarely work in isolation and need to be considered within a broader personalised management strategy, including self-management. Pharmacological and non-pharmacological interventions should be considered with a clear understanding of the potential outcomes and endpoints. These may well include: psychology, physiotherapy, drugs and more invasive interventions.

Treatment philosophy

Providing information that is personalised and responsive to the patient’s problems, conveying belief and concern, is a powerful way to allay anxiety [303]. Additional written information or direction to reliable sources of information is useful; practitioners tend to rely on locally produced material or pharmaceutical products of variable quality while endorsing the need for independent materials for patients [304].

5.1. Conservative management

5.1.1. Pain education

It is always valuable to include education about the causes of pain, including eliciting from patients their anxieties about undiscovered pathology and addressing them. Information improves adherence to treatment and underpins self-management, as shown in bladder pain syndrome and in many other painful and nonpainful disorders [305].

5.1.2. Physical therapy

The physiotherapist is part of the pain management team; (including doctors, psychologists and nurses). The therapeutic options for physiotherapists may not be the same in every country. Physiotherapists can either specifically treat the pathology of the pelvic floor muscles, or more generally treat myofascial pain if it is part of the pelvic pain syndrome. In most studies that have been done looking at the effect of physiotherapy in pelvic pain, the treatment of the pelvic floor is only part of the pain management. In a review about physiotherapy in women with pelvic pain, it was concluded that recommendations for physiotherapy should be given with caution [306]. The review found six RCTs, of which three showed level 1b evidence with low-risk of bias. One of these three found that Mensendieck somatocognitive therapy showed a pain reduction after one year follow-up of 64%. This approach consists of myofascial relaxation and tension, improving posture and movement in combination with cognitive behaviour therapy (CBT) [307].

Pelvic floor muscle pain

Treating pelvic floor over-activity and myofascial trigger points should be considered in the management of chronic pelvic pain. Treatment should be done by specialised physiotherapists who are trained not only in the musculoskeletal aspects of pain, but also in the psychological mechanisms and the role of the CNS in chronic pain.

For patients with chronic pelvic pain and dysfunction of the pelvic floor muscles, it is very helpful to learn how to relax the muscles when the pain starts. By doing this, the circle of pain-spasm-pain can be interrupted. In the case of shortened muscles, relaxation alone is not enough. Stretching of the muscle is mandatory to regain length and function. Studies on physical therapy for pelvic floor pain syndrome have been sparse. A single blinded RCT with myofascial physical therapy and general body massage was carried out in patients with prostate or bladder pain. The global response rate (RR) to treatment with massage was significantly better in the prostate than in the bladder pain group (57% vs. 21%). In the prostate pain group, there was no difference between the two treatment arms. In the bladder pain group, myofascial treatment did significantly better than massage. Massage only improved complaints in the prostate pain group. The fact that gender distribution was different in each group is mentioned as a possible confounding factor [308]. In an RCT of 84 patients with PPPS comparing so-called conventional therapy (α-blockers, anti-inflammatory drugs and sitz baths) with biofeedback and pelvic floor muscle relaxation therapy, the authors were able to demonstrate an improvement in both groups after three months, but three months after the end of treatment, the effects only persisted in the biofeedback and pelvic floor muscle relaxation therapy patients [309].

Myofascial trigger point release

Treatment of myofascial trigger points can be done by manual therapy, dry needling and wet needling. The evidence for all the different treatments is weak, with most studies showing no significant difference between these techniques, though most studies were small and heterogeneous with regards to the patients and methods. There is no evidence that manual techniques are more effective than no treatment [310]. Most studies of dry needling have compared with wet needling. Different SRs have come to the conclusion that, although there is an effect of needling on pain, it is neither supported nor refuted that this effect is better than placebo [311].

Physiotherapy in PBPS

Transvaginal manual therapy of the pelvic floor musculature (Thiele massage) in PBPS patients with high-tone dysfunction of the pelvic floor significantly improved several assessment scales [312]. The role of specific levator ani trigger point injections in women with chronic pelvic pain has been studied [313]. Each trigger point was identified by intravaginal palpation and injected with bupivacaine, lidocaine and triamcinolone. Seventy-two percent of women improved with the first trigger point injection, with 33% being completely pain-free. Efficacy and safety of pelvic floor myofascial physical therapy has been compared with global therapeutic massage in women with PBPS; global response assessment (GRA) rate was 59% and 26%, respectively. Pain, urgency and frequency ratings, and symptoms decreased in both groups during follow-up, and did not differ significantly between the groups. This suggests that myofascial physical therapy is beneficial in women with PBPS [314].

Primary Anal Pain Syndrome

An RCT demonstrated that biofeedback treatment was superior to electrogalvanic stimulation and massage of the Levator muscle for treating chronic primary anal pain syndrome [119]. One hundred and fifty-seven patients who had at least weekly rectal pain were investigated, but only patients with tenderness on traction of the pelvic floor showed a significant treatment benefit. In patients with tenderness of the puborectalis muscle (Rome II: “Highly likely Levator Ani Syndrome”), 87% reported adequate relief after one month of biofeedback vs. 45% for electrogalvanic stimulation, and 22% for massage. These results were maintained at twelve months with adequate relief after nine sessions of biofeedback in 58% of the whole group (Rome II: “Highly likely” and “Possible Levator Ani Syndrome”), after galvanic stimulation in 27% and massage in 21% of patients. As previously described in dyssynergic defecation, the ability to expel a 50 mL water filled balloon and to relax pelvic floor muscles after biofeedback treatment were predictive of a favourable therapeutic outcome [119]. The pathophysiology of the chronic primary anal pain syndrome is therefore similar to that of dyssynergic defecation, and this favours the role of the pelvic floor muscles in the pathophysiology of both conditions. Other treatment modalities have been less successful.

Treatment of sexual dysfunctions and chronic pelvic pain

Couples often benefit from early referral for relationship and sexual counselling during their treatment course [315]. It needs to be remembered that sexual difficulties will arise as a result of pelvic pain syndromes as well as those disorders potentially being primary. Specific behavioural strategies for women who have urogenital complaints and female sexual dysfunction often include exploring alternatives to sexual intercourse (manual or oral pleasuring), different coital positions (female superior or side lying), and pacing, such as limiting the activity to less than that which causes pain. Planning for the time of intercourse is important, and scheduling a clinic visit after intercourse might be useful to identify specific sites and causes of post-coital flares. The corresponding evidence in men is lacking, but similar principles would apply. Other behavioural changes involve pre- and post-coital voiding, application of ice packs to the genital or suprapubic area [315,316], and increased use of vaginal dilators, fingers or sex toys. Lubricants can also be used and women with signs of vulvovaginal atrophy may benefit from oestrogen cream [317]. Optimising the pelvic floor muscle is indicated when dysfunction is present and will relieve the pain [318-320].

Other physical therapy interventions

Electromagnetic therapy. A small, sham-controlled, double-blind study of four weeks showed a significant, sustained effect over a one-year period for CPPPS [321].

Microwave thermotherapy. In uncontrolled studies significant symptomatic improvement has been reported from heat therapy, for example, transrectal and transurethral thermotherapy [322,323].

Extracorporeal shockwave therapy. A small sham-controlled double-blind study of four times weekly perineal extracorporeal shockwave therapy (n=30) in men with CPPPS showed significant improvement in pain, QoL, and voiding compared to the control group (n=30), over twelve weeks [324]. Two other randomised sham-controlled studies, have been published more recently, one comparing ten treatment sessions over two weeks (n=40 vs. n=40) [325], another with four times weekly treatments (n=20 vs. n=20) [326]. Both concluded there was a significant effect in terms of total NIH-CPSI score and pain at twelve weeks. Unfortunately, no long term effects at 24 weeks could be shown in a published follow-up study of the second [327]. A Cochrane review of non-pharmacological interventions for chronic pelvic pain reported a reduction in symptoms following treatment compared with control and concluded that extracorporeal shockwave therapy may improve symptoms without an increase in adverse events [328]. In addition, a recent SR and meta-analysis concluded that extracorporeal shockwave therapy is effective for the improvement of pain and quality of life, but longterm efficacy was non-significant [329]. Publications show a potential role for external shock wave lithotripsy applied to the bladder. In an RCT enrolling 54 patients, improvement in the VAS > 3 was 57.1% vs. 19.0% (ESWT vs. placebo; P =.011), at 12 weeks post treatment. However, the primary endpoint did not reach significance [330].

Acupuncture. An RCT comparing acupuncture (n=50) vs. shamcontrolled (n=50), once weekly treatment for six weeks showed significant long lasting improvement at 24 weeks in terms of RR and overall symptom scores [331]. Another RCT showed a significant effect for a follow-up of 32 weeks [332]. Two SRs and meta-analyses were published in 2016 analysing seven RCTs on a total of 471 participants comparing acupuncture to sham control or oral medical treatment [333,334]. Both came to the conclusion that acupuncture was effective and safe, significantly reducing total NIH-CPSI scores compared to sham or medical treatment, and should be considered as a treatment option. This is in line with the conclusion of a Cochrane review [328] on non-pharmacological treatment options. In a large multicentre RCT comparing acupuncture (N=220) with sham acupuncture (N=220) in patients with PPPS over a period of 8 weeks (20 sessions), the authors could show a superior improvement of symptoms in the acupuncture group with durable effects 24 weeks after treatment [335]. In a more recently published SR and meta-analysis of only high quality trials (JADAD score >=4), the authors concluded that acupuncture compared to sham acupuncture was superior in terms of pain score, NIH-CPSI score, quality of life score, urinary symptom, and efficacy rate [336].

Posterior tibial nerve stimulation. See section 5.3.2, Neuromodulation.

Transcutaneous electrical nerve stimulation. See section 5.3.2, Neuromodulation.

5.1.3. Psychological therapy

Psychological interventions may be directed at pain itself or at adjustment to pain in terms of function and mood and reduced health-care use, with or without pain reduction. Ideally, treatment follows general principles and practice in the field of chronic pain [337,338] but these have been neglected in pelvic pain. Three SRs and meta-analyses of the few heterogeneous trials of psychologically based treatment for pelvic pain [339-341] found benefits for pain comparable to those from pharmacotherapy over a few months, but this was not sustained at follow-up. Exposure to pain-related fears in women with chronic pelvic pain proved superior to manual therapy in reducing those fears and overall pain disability, albeit assessed only by self-report [342]. The importance of multi-disciplinary treatment is emphasised by several reviews [44,343,344] of intervention for diverse chronic pains, but standard multi-component psychologically-based programmes for pelvic pains are mostly in the pilot stages [345], with mixed findings so far [346]. For primary focal vulvar pain syndrome, multimodal physiotherapy integrating psychological components has shown beneficial effects, although more research on the effects of psychological therapy and multi-component psychologically-based programmes is needed in this patient group [347]. For less disabled and distressed patients treatment can be delivered remotely [348,349].

5.1.4. Dietary treatment

Scientific data are limited and dietary restriction alone does not produce significant symptomatic relief; however, consider the involvement of a dietician.

5.2. Pharmacological management

5.2.1. Drugs for chronic primary pelvic pain syndrome

In this section the evidence available for specific CPPPSs is presented. Where there is no evidence the reader is directed to the section on analgesics below (Section 5.2.2) where more generic use is discussed. There is a large discrepancy in the treatment effects reported in case series and controlled trials that results from a large placebo effect or publication bias. As a result of the multifactorial origin of for example PPPS, one reason for treatment failure in some large placebo-controlled RCTs, may be the heterogeneity of the patient population [350]. One strategy for improving treatment effects may be stratification of patient phenotypes. A prospective series of phenotypically directed treatment for CPPPS has shown significant improvement of symptoms and QoL [351]. Monotherapeutic strategies for the treatment of CPPPS may fail [352], therefore, most patients require multimodal treatment aimed at the main symptoms, and taking comorbidity into account. In the past ten years, results from RCTs have led to advances in standard and novel treatment options.

5.2.1.1. Mechanisms of action

Mechanisms of action are discussed as appropriate under the drugs headings below.

5.2.1.2. Comparisons of agents used in pelvic pain syndromes

Primary Prostate Pain Syndrome (PPPS)Anti-inflammatory drugs

For non-steroidal anti-inflammatory agents (NSAIDs), a trial with celecoxib reported that the pain sub-score, QoL sub-score, and total NIH-CPSI score were in favour of the treatment arm vs. placebo, but effects were limited to the duration of therapy [353]. In a meta-analysis, two studies of NSAIDs [259,353] and one with prednisolone [354] were pooled. Anti-inflammatory drugs were 80% more likely to have a favourable response than placebo. In an updated network meta-analysis with more restrictive inclusion criteria regarding documented outcome measures but a wider spectrum of drugs (including glycosaminoglycans, phytotherapy and tanezumab), a significant effect on total NIH-CPSI scores and treatment response rates could be demonstrated. A Cochrane SR from 2019 concluded that anti-inflammatories may reduce prostatitis symptoms compared to placebo [355]. Overall, a moderate treatment effect has been shown for anti-inflammatory drugs, but larger studies are needed for confirmation, and long-term side-effects have to be taken into account.

α-blockers

Positive results from RCTs of α-blockers, i.e. terazosin [356,357], alfuzosin [358], doxazosin [359,360], tamsulosin [361,362], and silodosin [363] have led to widespread use of α-antagonists in the treatment of PPPS in recent years. Whereas one SR and meta-analysis has not reported a relevant effect of α-blockers due to study heterogeneity [364], another network meta-analysis of α-blockers [363] has shown significant improvement in total symptoms, pain, voiding, and QoL scores. In addition, they had a higher rate of favourable response compared to placebo [relative risk (RR): 1.4; 95% CI: 1.1-1.8, p=0.013]. However, treatment responsiveness, i.e., clinically perceptive or significant improvement, may be lower than expected from the change in mean symptom scores. Overall, α-blockers seem to have moderate but significant beneficial effects. This probably is not the case for long-standing PPPS patients [365]. A Cochrane Systematic review published in 2019 reported an uncertain treatment effect of α-blockers on “prostatitis” symptoms, and little to no difference in sexual dysfunction, quality of life, anxiety and depression [355]. Future studies should show if longer duration of therapy or some sort of phenotypically directed (e.g., patients with PPPS and relevant voiding dysfunction) treatment strategies will improve treatment outcomes.

Antibiotic therapy

Empirical antibiotic therapy is widely used because some patients have improved with antimicrobial therapy. Patients responding to antibiotics should be maintained on medication for four to six weeks or even longer. Unfortunately, culture, leukocyte and antibody status of prostate-specific specimens do not predict antibiotic response in patients with PPS [366], and prostate biopsy culture findings do not differ from those of healthy controls [367]. The only placebo-controlled RCTs of sufficient quality have been done for oral antibiotic treatment with ciprofloxacin (six weeks) [368], levofloxacin (six weeks) [369], and tetracycline hydrochloride (twelve weeks) [370]. The studies have been analysed in meta-analyses [363,371]. Although direct meta-analysis has not shown significant differences in outcome measures, network meta-analysis has suggested significant effects in decreasing total symptom, pain, voiding, and QoL scores compared with placebo. Combination therapy of antibiotics with α-blockers has shown even better outcomes in network meta-analysis. Despite significant improvement in symptom scores, antibiotic therapy did not lead to statistically significant higher response rates [371]. In addition, the sample sizes of the studies were relatively small and treatment effects only modest, mostly below clinical significance. It may be speculated that patients profiting from treatment had some unrecognised uropathogens. A Cochrane SR reported that antibiotics may reduce “prostatitis” symptoms compared to placebo [355]. If antibiotics are used, other therapeutic options should be offered after one unsuccessful course of a quinolone or tetracycline antibiotic over six weeks. In addition, it is very important that unnecessary antibiotic use is avoided and local resistance patterns are considered. In this regard, the relevant recommendations of the EAU Guidelines on Urological Infections should be followed [372].

5-α-reductase inhibitors

Although a few small pilot studies with 5-α-reductase inhibitors supported the view that finasteride may improve voiding and pain, the first RCT published in a peer-reviewed journal did not support this, although the study lacked power [373]. In another RCT, finasteride provided better amelioration of symptoms compared to saw palmetto over a one-year period, but lacked a placebo-control arm [374]. A six-month placebo-controlled study showed a non-significant tendency towards better outcome in favour of finasteride, possibly because of a lack of statistical power [362]. A Cochrane review concluded that finasteride probably reduces prostatitis symptoms compared to placebo [355]. The NIH-CPSI scores decreased significantly in a subgroup of men enrolled in a prostate cancer risk reduction study treated with dutasteride compared to placebo [363]. Patients (n=427, age 50 to 75, with elevated prostate-specific antigen [PSA]) were included if they had significant “prostatitis like” symptoms at baseline. Based on the evidence, 5-α-reductase inhibitors cannot be recommended for use in PPPS in general, but symptom scores may be reduced in a restricted group of older men with an elevated PSA [363].

Phytotherapy

Phytotherapy applies scientific research to the practice of herbal medicine. An adequately powered placebocontrolled RCT of a pollen extract (Cernilton) showed clinically significant symptom improvement over a twelve week period in inflammatory PPPS patients (NIH Cat. IIIA) [375]. The effect was mainly based on a significant effect on pain. Another pollen extract (DEPROX 500) has been shown to significantly improve total symptoms, pain and QoL compared to ibuprofen [376]. In an RCT of patients treated with pollen extract suppositories (n=70) vs. oral ibupofen (n=71) over a period of ten days, the authors could find a clinically significant effect up to six months of follow-up including fewer adverse events in the pollen extract group [377]. A SR and meta-analysis of pollen extract for the treatment of PPPS showed significant improvement in overall QoL [378]. As an adjunct to α-blocker therapy, cernitin pollen extract proved superior to tadalafil in terms of pelvic pain and discomfort [379]. Quercetin, a polyphenolic bioflavonoid with documented antioxidant and anti-inflammatory properties, improved NIH-CPSI scores significantly in a small RCT [380]. In a large multicentre trial of 221 patients over twelve weeks, saw palmetto extract (Serenoa repens) led to statistically significant improvement in the NIH-CPSI total score and sub-scores compared to placebo [381]. In a SR and meta-analysis, patients treated with phytotherapy were found to have significantly lower pain scores than those treated with placebo [363]. In addition, overall RR in network meta-analysis was in favour of phytotherapy (RR: 1.6; 95% CI: 1.1-1.6).

Pregabalin is an anti-epileptic drug that has been approved for use in neuropathic pain. In an adequately powered placebo-controlled RCT, which was the only report included in a published Cochrane review [382], a six-week course of pregabalin (n=218) compared to placebo (n=106) did not result in a significant reduction of NIH-CPSI total score [383]. This group thinks it may have a role in selected patients and should be used in accordance with the paragraph 5.2.22

Pentosane polysulphate is a semi-synthetic drug manufactured from beech-wood hemicellulose. One study using oral high-dose (3 x 300 mg/day) demonstrated a significant improvement in clinical global assessment and QoL over placebo in men with PPPS, suggesting a possible common aetiology [384].

Muscle relaxants (diazepam, baclofen) are claimed to be helpful in sphincter dysfunction or pelvic floor/perineal muscle spasm, but there have been few prospective clinical trials to support these claims. In one RCT, a triple combination of a muscle relaxant (thiocolchicoside), an anti-inflammatory drug (ibuprofen) and an α-blocker (doxazosin) was effective in treatment-naïve patients, but not superior to an α-blocker alone [360].

Botulinum toxin type A (BTX-A) for the treatment of CPPPS is an off-label use, but a recent SR identified two RCTs and one non-randomised comparative study assessing intraprostatic BTX-A injections (100-200 units) for treatment of PPPS [385]. All three papers used the NIH-CPSI to score pain. Although two of the studies reported a statistically significant reduction in pain, incomplete data and differences in dose and study methodology precluded calculation of a summary effect estimate for BTX-A-related improvement in pain. No definitive conclusions could be drawn from the review.

Zafirlukast, a leukotriene antagonist, and prednisone in two low-power placebo-controlled studies failed to show a benefit [354,386]. More recently, a placebo-controlled phase II a study of tanezumab, a humanised monoclonal antibody that specifically inhibits the pain mediating neurotrophin, nerve growth factor, failed to demonstrate significant effect [387] and should only be used in clinical trials.

Allopurinol

There is insufficient evidence for the use of allopurinol in PPPS [388,389].

Primary Bladder Pain Syndrome (PBPS)Treatments of significant value for PBPSAnti-histamines

Mast cells may play a role in PBPS. Histamine is one of the substances released by mast cells. Histamine receptor antagonists have been used to block the H1 and H2 receptor subtypes, with variable results. A prospective placebo-controlled RCT of hydroxyzine or oral pentosane polysulphate did not show a significant effect [390].

Amitriptyline

Amitriptyline is a tricyclic antidepressant. Several reports have indicated improvement of PBPS symptoms after oral amitriptyline. Amitriptyline has been shown to be beneficial when compared with placebo plus behavioural modification [391]. Drowsiness is a limiting factor with amitriptyline, nortriptyline is sometimes considered instead.

Pentosane polysulphate

Pentosan polysulphate is a semi-synthetic drug manufactured from beech-wood hemicellulose. Subjective improvement of pain, urgency, frequency, but not nocturia, has been reported [392,393]. Pentosane polysulphate had a more favourable effect in PBPS type 3 C than in non-lesion disease [394]. Response was not dose dependent but related more to treatment duration. At 32 weeks, about half the patients responded. Combination therapy showed a RR of 40% compared to 13% with placebo. For patients with an initial minor response to pentosane polysulphate, additional subcutaneous heparin was helpful [395,396].

Immunosuppressants

Azathioprine treatment has resulted in disappearance of pain and urinary frequency [397]. Initial evaluation of methotrexate [398] showed good analgesic effect but limited efficacy for urgency and frequency. Corticosteroids are not recommended in the management of patients with PBPS because of a lack of evidence.

Intravesical Treatments

Intravesical drugs are administered due to poor oral bio-availability establishing high drug concentrations within the bladder, with few systemic side-effects. Disadvantages include the need for intermittent catheterisation which can be painful in PBPS patients, cost and risk of infection.

• Local anaesthetics

There are sporadic reports of successful treatment of PBPS with intravesical lidocaine [399,400]. Alkalisation of lidocaine improves its pharmacokinetics [401]. Combination of heparin, lidocaine and sodium bicarbonate gave immediate symptom relief in 94% of patients and sustained relief after two weeks in 80% [402]. Intravesical instillation of alkalised lidocaine or placebo for five consecutive days resulted in significantly sustained symptom relief for up to one month [403].

• Hyaluronic acid and chondroitin sulphate

These are described to repair defects in the GAG layer. Despite the fact that intravesical GAG replenishment has been in use for about twenty years for PBPS/IC, most of the studies are uncontrolled and with a small number of patients. Based on the studies available there are differences by virtue of substance classes, whether they are natural GAG layer components, dosage formulations, or concentrations. An RCT seems to reinforce the case for GAG layer replenishment, however it lacks a placebo arm [404]. A meta-analysis confirms usefulness of GAG layer replenishment [412]. However, most retrieved studies are non-randomised and with scarce numbers.

• Intravesical heparin

Primary bladder pain syndrome patients were treated with heparin for three months, and over half had control of symptoms, with continued improvement after one year of therapy [405]. Intravesical heparin plus peripheral neuromodulation in patients with refractory PBPS was studied and it was shown that voiding frequency, pain score and maximum cystometric capacity were significantly better after two and twelve months [406].

• Hyperbaric oxygen

This has a moderate effect on a small subgroup of PBPS patients. Disadvantages include high cost, limited availability of treatment sites, and time-consuming treatment [395].

Treatments of limited value for PBPSCimetidine

There are limited data to suggest that cimetidine improves symptoms of PBPS in the short-term. Compared with placebo for three months, cimetidine significantly improved symptom scores, pain and nocturia, although the bladder mucosa showed no histological changes in either group [407].

Prostaglandins

Misoprostol is a prostaglandin that regulates various immunological cascades. After three months of treatment with misoprostol, fourteen out of 25 patients had significantly improved, with twelve showing a sustained response after a further six months [408]. The incidence of adverse drug effects was 64%.

L-Arginine

Oral treatment with the nitric oxide (NO) synthase substrate L-arginine was suggested to decrease PBPS-related symptoms. However, no symptomatic relief or change in NO production could be shown after treatment [409,410].

Oxybutynin is an anti-cholinergic drug used in overactive detrusor dysfunction. Intravesical oxybutynin combined with bladder training improves functional bladder capacity, volume at first sensation, and cystometric bladder capacity [411]. However, an effect on pain has not been reported.

Duloxetine (a serotonin-noradrenaline re-uptake inhibitor antidepressant with a licence for the management of neuropathic pain) did not significantly improve symptoms of PBPS [412]. Administration was safe. Based on these preliminary data, duloxetine cannot be recommended for treatment of PBPS.

PDE5 inhibitors are drugs currently used for erectile dysfunction. In different RCT improved all parameters evaluated at twelve weeks, but at 24 weeks results were not consistent for pain VAS score [413]. Using a PDE5i, theoretically, the activation of C fiber is decreased, bladder afferent activity is reduced and detrusor muscle tone relaxes.

Primary Scrotal Pain Syndrome (PSPS)

Treatment of primary scrotal pain syndrome is based on the principles of treating chronic pain syndromes, as described throughout these guidelines.

In men with pain post inguinal hernia repair, there is limited evidence from case series showing that neurectomy of the damaged nerves can lead to symptomatic benefit [185,414].

For scrotal pain post vasectomy, affected men may find that reversal of vasectomy can cure symptoms especially in those in whom patency is achieved [415]. In a prospective RCT, pulsed radio-frequency to the ilioinguinal and genitofemoral nerves is associated with high rates of symptomatic improvement (80%) but follow up was limited to three months [416]. The evidence for epididymectomy is poor but if considered, is less likely to provide benefit if the epididymis has a normal sonographic appearance [417].

Chronic gynaecological pain

It is difficult to compare the wide variation of drugs from an efficacy and safety perspective as they have such diverse uses/indications. In those gynaecological patients where chronic pelvic pain is unrelated to any of the well-defined conditions, it is often difficult to determine a therapeutic pathway other than a multidisciplinary chronic abdomino-pelvic pain management plan. A Cochrane review suggests there may be some evidence (moderate) supporting the use of progestogens [340]. Though efficacious, physicians need to be knowledgeable of progestogenic side effects (e.g., weight gain, bloatedness - the most common adverse effects) which can stop some patients from accepting such medication. Gonadotropin-releasing hormone (GnRH), such as goserelin, are also thought to help such pain. However, when compared with progestogens, their efficacy remains limited. The quality of evidence is generally low and drawn from single studies [340]. Gonadotropin-releasing hormone on the other hand binds to specific receptors on pituitary gonadotrophs, leading to desensitisation and consequently to suppressed gonadotropin secretion. By contrast, GnRH antagonists compete with GnRH for receptors thus gonadotrophin secretion, which may be beneficial in certain clinical applications, such as reducing the size of fibroids, endometrial bleeding and endometriosis [418].

Pelvic Floor, Abdominal and Chronic Anal PainBotulinum toxin type A (pelvic floor)

Pelvic floor muscle over-activity plays a role in CPPPS. Botulinum toxin type A, as a muscle relaxant, can be used to reduce the resting pressure of the pelvic floor muscles and injection of the puborectalis and pubococcygeus muscles has been used to treat spasm of the levator ani A pilot study of twelve women with pelvic floor muscle overactivity as defined by a vaginal resting pressure > 40 cm H2O on vaginal manometry reported a reduction in resting pressure with improvement in dyspareunia and dysmenorrhoea, but no significant changes in non-menstrual pelvic pain scores [419]. A SR including three RCTs comparing BTX-A with saline injections into the pelvic floor found no benefit in pain scores at six months follow-up despite a reduction in pelvic floor pressure [385].

Botulinum toxin type A has been injected into trigger points. It is more expensive than lidocaine and has not been proven to be more effective [420]. Reviews do not support the injection of BTX-A into trigger points [421].

Botulinum toxin type A can also be injected at the sphincter level to improve urination or defecation. Relaxation of the urethral sphincter alleviates bladder problems and secondarily the spasm. In a cohort study of thirteen patients with CPPPS, BTX-A was injected into the external urethral sphincter. Subjectively, eleven patients reported a substantial change in pain symptoms, from a score of 7.2 to 1.6 on a VAS [422].

Intermittent chronic primary anal pain syndrome

Due to the short duration of the episodes, medical treatment and prevention is often not feasible. Inhaled β-2 adrenergic agonist salbutamol was effective in an RCT in patients with frequent symptoms and shortened pain duration [423]. Other treatment options are topic diltiazem and BTX-A [424]. However, there is still some controversy regarding the duration of pain of intermittent chronic and chronic primary anal pain syndrome. Randomised controlled trials often use different definitions, extending the pain duration (with a shift to chronic pain) in order to include more patients and to better evaluate the study-drug action.

Abdominal pain associated with Irritable Bowel Syndrome

Linaclotide, a minimally absorbed peptide guanylate cyclase-C agonist at a dose of 290 μg once daily significantly improved abdominal pain (48.9% vs. 34.5% placebo-treated) and bowel symptoms associated with IBS with constipation over 26 weeks of treatment [425]. Diarrhoea was the most common adverse event in patients treated with linaclotide (4.5%). Although it is known to overlap with IBS pelvic pain, effect on the latter was not assessed in this study.

In a Cochrane Meta-analysis antispasmodics had a beneficial effect for improvement of abdominal pain compared to placebo (58% improved on antispasmodic compared to 46% on placebo) in IBS [426]. Peppermint oil showed in a meta-analysis of nine RCT’s improvement in abdominal pain in patients with IBS [427].

5.2.2. Analgesics

If the use of simple analgesics fails to provide adequate benefit, then consider using neuropathic agents, and if there is no improvement, consider involving a specialist pain management centre with an interest in pelvic pain. Chronic pelvic pain is well defined and involves multiple mechanisms as described in previous sections.

The management requires a holistic approach with biological, psychological and social components. Few studies have specifically looked at medications used in CPPPS [428], therefore, a wider look at the literature has been undertaken and further specific research is required. The agents concerned are divided for ease of description. Combinations often provide a greater benefit than individual agents [429]. They may also allow lower individual dosages and thus minimise side-effects. The aim of using these drugs is to allow patients to improve their QoL. This is best measured by assessing their function as well as pain severity. If the use of these agents does not allow this, then they should be withdrawn. Unfortunately, the failure of one agent does not exclude potential benefit of an alternative. If the benefit is limited by side-effects, then the lowest effective dose should be found (by dose titration). Sometimes, patients will prefer a higher level of pain and have fewer side effects.

5.2.2.1. Mechanisms of action

Mechanisms of action are discussed as appropriate under the drug headings below.

5.2.2.2. Comparisons within and between groups in terms of efficacy and safety

Paracetamol (acetaminophen)

Paracetamol is a well-tolerated analgesic in a class of its own. This is an antipyretic analgesic with a central mechanism of action [430]. It is often available over the counter without prescription. A review questions its routine use as a first-line analgesic based on inadequate evidence of efficacy in many pain conditions including dysmenorrhoea [431]. It will not be effective for all patients and individual responses should be reviewed when deciding on longer term use.

Non-steroidal anti-inflammatory agents

These agents are anti-inflammatory, antipyretic analgesics that act by inhibiting the enzyme cyclooxygenase (COX). They have a peripheral effect, hence their use in conditions involving peripheral or inflammatory mechanisms. They are commonly used for pelvic pain; many are available over the counter and are usually well-tolerated. There is insufficient evidence to suggest one NSAID over another for pelvic pain. Guidelines for use of NSAIDs and COX-2 selective agents have been developed. They have more side-effects than paracetamol, including indigestion, headaches and drowsiness.

The evidence for their benefit in chronic pelvic pain is weak or non-existent and is often limited by side-effects. For pelvic pain in which inflammatory processes are considered important, such as dysmenorrhoea [432], NSAIDs are more effective than placebo and paracetamol, but with a higher incidence of side-effects. For pelvic pain in which central mechanisms may be incriminated, such as endometriosis [433] then the evidence is lacking for NSAIDs despite their common use.

At a practical level, if NSAIDs are considered for use, they should be tried (having regard for the cautions and contraindications) and the patient reviewed for improvement in function as well as analgesia. If this is not achieved, or side-effects are limiting, then they should be withdrawn.

Neuromodulators

These agents are not simple analgesics but used to modulate neuropathic or centrally mediated pain. There are several classes commonly used with recognised benefits in pain medicine. They are taken on a regular basis and all have side-effects that may limit their use and have the potential to be dependence-forming. In the UK, NICE has reviewed the pharmacological management of neuropathic pain [434]. The evidence for treatment of CPPPS is lacking but is present for other painful conditions. For this chapter, most of the evidence is from non-pelvic pain sources. The general method for using these agents is by titrating the dose against benefit and side-effects. The aim is for patients to have an improvement in their QoL, which is often best assessed by alterations in their function. It is common to use these agents in combination but studies comparing different agents against each other, or in combination, are lacking. Some of these agents are also used for specific conditions. Early identification of neuropathic pain with a simple questionnaire could facilitate targeted therapy with neuromodulators [58].

AntidepressantsTricyclic antidepressants

The tricyclic antidepressants (TCAs) have multiple mechanisms of action and are frequently limited by their side-effects. Tricyclic antidepressants have a long history of use in pain medicine and have been subjected to a Cochrane review [435], suggesting that they are effective for neuropathic pain. Amitriptyline is the most commonly used at doses from 10-75 mg/day (sometimes rising to 150 mg/day). This is titrated against benefit or side-effects and should be taken at night [434]. Nortriptyline and imipramine are used as alternatives.

Other Antidepressants

Duloxetine is a SNRI antidepressant licensed for use in depression, SUI and neuropathic pain. There is evidence of benefit in diabetic neuropathy and fibromyalgia at a dose of 60 mg/day [436,437]. Side-effects are common and may result in its discontinuation.

Anticonvulsants

Anticonvulsants are commonly used in the management of neuropathic pain. There are general studies and some looking more particularly at pelvic pain. Individual agents have been systematically reviewed. Their use is suggested in the NICE Neuropathic Pain Guidelines [434].

Carbamazepine has a long history of use in neuropathic pain. Evidence exists for its benefit [438]. Trials trend to be of short duration, showing only moderate benefit. There are side-effects; some of which may be serious. It is no longer a first choice agent. Other anticonvulsant agents are available with fewer serious side-effects.

Gabapentinoids
There is a growing awareness and evidence of the risk for dependence and misuse of gabapentinoids [439]. A formal assessment of efficacy against benefit and side-effects (both pain and QoL) is required with the patient in order to determine the lowest effective dose and if longer-term treatment is to be used.

Gabapentin is commonly used for neuropathic pain and has been systematically reviewed [440,441]. This demonstrates good evidence for postherpetic neuralgia and diabetic neuropathy but evidence for other neuropathies is limited. A double-blind RCT looking at CPPPS in women with no obvious pathology demonstrated no benefits but higher levels of side effect [441].

Pregabalin is a commonly used neuromodulator with good evidence of efficacy in some neuropathic conditions [442]. The dose for benefit is in the range of 300-600 mg/day. Evidence for central neuropathic pains is inadequate. Some patients do gain moderate to significant benefit but most will gain no benefit and then the drug should be discontinued. Other agents can be used in the management of neuropathic pain but they are best administered by specialists in the management of pain whom are familiar with their use. They tend to be considered after the standard options have been exhausted. As with all good pain management, they are used as part of a comprehensive multi-dimensional management plan.

Opioids

Over recent years opioids have been used extensively for managing chronic non-cancer pain. There is increasing evidence that their role is limited in this population, but may be beneficial for a small number of patients at a low dose in a managed setting [443]. There is clear evidence of harm and significant professional, public and political interest. Their use is beneficial for both acute pain and for cancer pain management particularly towards the end of life.

Often patients will stop taking oral opioids due to side effects or insufficient analgesic effect [444]. There is clear evidence of harm including effects on the endocrine and immune systems as well as a growing understanding of opioid-induced hyperalgesia [445]. There is limited guidance on the best method for tapering the dose of opioids with the aim of stopping or finding the lowest effective dose [446].

Opioids should only be used in conjunction with a management plan with consultation between clinicians experienced in their use. It is suggested that a pain management unit should be involved along with the patient and their primary care physician. Ensure there are arrangements for formal monitoring, follow-up and review. If opioids are used and the pain remains, then they are not working and should be stopped even if there is no alternative [445].

The risk of harm increases substantially at doses above 120 mg/day morphine equivalence [445] and guidance suggests regular (at least annual) review for patients with over 50 mg/day morphine equivalence and pain specialist involvement above 90 mg/day morphine equivalence [447].

There are well-established guidelines for the use of opioids in pain management as well as considering the potential risks [445,447]. Opioid reduction and optimisation should be undertaken where opioids are not providing clear measurable benefit. There is also information available online for patients [445]. Opioids Aware is a web-based resource for patients and healthcare professionals, jointly produced by the Faculty of Pain Medicine of Royal College of Anaesthetists and Public Health England, to support prescribing of opioid medicines for pain. https://fpm.ac.uk/opioids-aware.

Cannabinoids

There has been increasing interest and changes in national regulations regarding the use of cannabinoids for medicinal use. Regarding pain the evidence base for the use of cannabinoids is weak [448-450] and further well conducted clinical trials are necessary. This is an area where further guidance and research is likely in the coming years.

5.3. Further management

5.3.1. Nerve blocks

Nerve blocks for pain management are usually carried out by specialists in pain medicine as part of a broader management plan [451]. They may have a diagnostic or therapeutic role. Textbooks have been written on the subject and practitioners using them should be trained in appropriate patient selection, indications, risks and benefits. Many such interventions also require understanding and expertise in using imaging techniques to perform the blocks accurately. Diagnostic blocks can be difficult to interpret due to the complex mechanisms underlying the painful condition or syndrome. Sustained but limited benefit may lead to more permanent procedures (e.g., radiofrequency procedures). There is a weak evidence base for these interventions for chronic non-malignant pain [452].

Pudendal Neuralgia

The role of injections may be divided into two. First, an injection of local anaesthetic with or without steroids at the sight of nerve injury or nerve entrapment may produce a therapeutic action [453,454]. The second possible benefit is diagnostic. It has already been indicated that when the pudendal nerve is injured there are several sites where this may occur. Differential block of the pudendal nerve helps to provide information in relation to the site where the nerve may be trapped [250,455-457].

Infiltration at the ischial spine requires the use of a nerve stimulator/locator. Both motor (anal contraction) and sensory endpoints may be noted. The anatomical endpoint may be localised by fluoroscopy, CT guidance, or the use of US, the latter avoids any radiation, whereas CT guidance involves a significant amount of radiation. Fluoroscopy and ultrasound guidance imaging are the most frequently used techniques for performing nerve block because it is readily available to most anaesthetists. Pulsed radio frequency lesioning for pudendal neuralgia is being developed with a paper demonstrating potential benefit. Follow-up is short term and further research is required to better elucidate its place in management [458].

5.3.2. Neuromodulation

The role of neuromodulation in the management of pelvic pain should only be considered by specialists in pelvic pain management. These techniques are used as part of a broader management plan and require regular follow-up. The research base is developing and the techniques broadening (e.g., spinal cord stimulation, sacral root stimulation, dorsal root ganglion stimulation or peripheral nerve stimulation). These are expensive interventional techniques for patients refractory to other therapies. Neuromodulation is still finding its role in pelvic pain management. There has been growing evidence but more detailed, high quality research is required [459]. Its role in overactive bladder (OAB) and faecal incontinence is more robust but is limited for pain. Two SRs have evaluated neuromodulation techniques for CPPS [460,461]. Both studies concluded that neuromodulation may be effective in reducing pain and improving QoL in patients with CPPS; however, studies were of a low quality and long-term results were needed.

Transcutaneous Electrical Nerve Stimulation

Transcutaneous electrical nerve stimulation (TENS) is a non-invasive technique used in many pain conditions. A SR identified twelve studies of TENS in chronic pelvic pain conditions including four RCTs [460]. All RCTs demonstrated a significant reduction in pain following twelve weeks of treatment for pain conditions including dysmenorrhoea and CPPPS. Pain was also found to improve following TENS for provoked vestibular pain. There was conflicting data with regard to improvement of QoL following TENS; where validated questionnaires were used, no significant improvement was found, whereas in trialist-defined studies, an improvement was seen in TENS for dysmenorrhea and CPPPS. The beneficial effects of a course of TENS may be sustained; one study demonstrating a persistent benefit at 43 months in 73% of men with CPPPS and another demonstrating a prolonged significant improvement in women with provoked vestibular pain at ten months post-treatment. Where reported there were no adverse events recorded. Transcutaneous electrical nerve stimulation could offer an effective non-invasive treatment option for patients with CPPPS.

Percutaneous Tibial Nerve Stimulation

Percutaneous tibial nerve stimulation (PTNS) is a minimally invasive technique that can be use in an outpatient setting. Two SRs have shown that PTNS is effective in reducing pain in patients with CPPPS [460,461]. Three RCTs identified showed a significant improvement in pain scores and QoL as measured by validated questionnaires. Where recorded, adverse events were rare and minor including temporary slight pain at application site and haematoma.

Sacral Nerve Stimulation

Sacral nerve stimulation (SNS) is an invasive technique requiring sedation or general anaesthesia for implantation of a device following trial stimulation. A SR review identified ten studies of SNS in CPPPS, either retrospective case series or prospective cohort studies and no RCTs. Where reported, a mean of 69% of participants progressed to implantation of device following test stimulation (range 52-91%). All studies reported an improvement in pain, statistically significant in five studies. Quality of Life was measured in three studies and a significant improvement demonstrated in two of three studies. There was a large variation in adverse events reported ranging from 0-50%. Complications not requiring surgical intervention included pain, failure of device, wound infection and seroma. Re-operation rate ranged between 11-50% for complications including lead migration, systemic infection, intrathecal implantation, loss of efficacy and erosion. In clinical practice, a patient should be appropriately counselled regarding the need for a period of trial stimulation and whilst there may be an improvement in symptoms, this should be weighed against a notable complication rate.

A SR review in 2018 identified fourteen studies. In all, 403 patients had undergone percutaneous nerve evaluation and/or SNM stage 1 and 54.8%) had progressed to the permanent implantation stage, which is similar to that reported previously. The cause of pain was reported to be IC/BPS in 170 cases (42.2%). Visual Analogue Scale pain scores were available pre- and post-SNM in 210 patients and overall improvement in pain scores was significant. Sacral nerve stimulation is a promising treatment option for refractory chronic pelvic pain. This is mainly supported by level 2b studies. Randomised prospective studies are warranted to compare SNS vs. other modalities for chronic pelvic pain treatment. Further studies are needed to compare antegrade vs. retrograde approaches [462].

Other neuromodulation techniques

A variety of other techniques of neuromodulation for patients with CPPPS were identified by SRs [460,463]. These techniques include intravaginal electrical stimulation for women with CPPPS, pudendal nerve stimulation for CPPPS, spinal cord stimulation for pudendal neuralgia, transcutaneous interferential electrical stimulation for IBS, electrical acupuncture for dysmenorrhoea and electrical stimulation/biofeedback and electromagnetic stimulation for men with CPPPS. Whilst an improvement in pain has been reported in these studies, it is noted that they are largely of low quality and further work is needed in this area to enable robust clinical recommendations to be made. Neuromodulation in combination with hormonal treatment in deep endometriosis may have some benefit [464].

5.3.3. Surgery

Primary Bladder Pain Syndrome (PBPS)Bladder distension

Although bladder hydrodistension is a common treatment for PBPS, the scientific justification is scarce. It can be part of the diagnostic evaluation, but has limited therapeutic role [465].

Hydrodistension and Botulinum toxin type A

Botulinum toxin type A may have an anti-nociceptive effect on bladder afferent pathways, producing symptomatic and urodynamic improvements [466]. Treatment with hydrodistension and hydrodistension plus intravesical BTX-A has been compared [467]. There was symptomatic improvement in all patients. However, in the hydrodistension-only group, 70% returned to their previous symptoms after one month, while in the BTX-A-treated patients, VAS score and functional and cystometric bladder capacity improved at three months. Botulinum toxin type A trigonal-only injection seems effective and long-lasting as 87% of patients reported improvement after three months follow-up [468]. Over 50% reported continued benefit nine months after the first treatment. When re-treatment was needed, similar results were obtained. Up to 59% of patients remain responders after 9 treatments. The sustained duration of the effect, despite the increase in the number of procedures, suggests that intratrigonal sensory neurons do not develop tolerance to OnaBotA, even during long periods of administration [469]. Adverse effects of BTX-A administration for IC/PBPS were significantly less than for OAB syndrome, namely in increased postvoid residual volumes and decreased voiding efficiency [470]. Recent RCTs have reported benefits and long efficacy of BTX-A administration [471-474], but a summary estimate for overall change in pain following BTX-A injections was not possible in a recent SR [385]. Conflicting data on results hinders issuance of a clear guideline for the use of Botox in PBPS phenetypes [475].

Results of treatment with intravesical plasma rich (PRP) injections are also being explored. A recent prospective trial, showed that patients with GRA (global response assessment) > 2, had success rates at one month and at three months after the fourth PRP injection, of 70.6% and 76.7%, respectively. The VAS pain score, frequency, and nocturia showed a significant decrease (all p < 0.05). However, further studies are needed to validate findings [476].

Transurethral resection, coagulation and laser ablation

Endourological destruction of bladder tissue aims to eliminate urothelial Hunner lesions. Coagulation of glomerulations or petequiae area is not recommended. Since the 1970s, resection and fulguration have been reported to achieve symptom relief, often for more than three years [477-479]. Repeated resection or fulguration treatments should be wisely indicated. A more recent study has shown no difference in therapeutic benefit between transurethral laser ablation or resection [479].

Major Surgery for PBPS 480

Primary bladder pain syndrome is a benign condition that can severely impact quality of life but does not shorten life expectancy. Consequently major operative procedures are ranked last in the therapeutic algorithm and are only appropriate as a last resort for patients with severe refractory disease. The level of evidence underpinning reconstructive surgery is weak with no consensus regarding the optimal surgical approach. A systematic review with 450 patients (90% female, median age 54.5 years) from 20 eligible studies reported symptomatic improvement in 77.2% of patients with an overall complication rate of 26.5% and a mortality of 1.3% [480]. This complication rate is likely to be an underestimate as a third of the procedures did not specify their complication data. All the studies included the systematic review were retrospective and observational with no control groups. There was also heterogeneity in the diagnostic criteria and outcome measures used. The main surgical options performed comprised:

1. Urinary diversion without cystectomy is performed to minimise the duration and complexity of surgery and preserve sexual function and fertility, but complications related to the retained bladder commonly occur with the incidence of pyocystis reported to range between 3.3% and 67%.
2. Subtotal (supratrigonal) cystectomy with substitution cystoplasty is the preferred reconstructive approach particularly in younger patients [481] and the use of various intestinal segments has been reported [482-484].
3. Total (subtrigonal) cystectomy and orthotopic neobladder formation has the benefit of removing the trigone as a possible disease site, but requires ureteric re-implantation. Trigonal disease is reported in 50% of patients and surgical failure has been blamed on the trigone being left in place [485], especially in patients with non-lesion type disease [486,487]. Incomplete emptying of the orthotopic bladder augmentation is most likely to occur following trigonal resection so intermittent self-catheterisation may be required [488]. A study on female sexuality after cystectomy and orthotopic ileal neobladder showed pain relief in all patients and improvement in sexual function items in women who remained sexually active [489]. Pregnancies with subsequent lower-segment Caesarean section have been reported after ileocystoplasty [490].
4. Cystectomy and ileal conduit formation avoids the increased surgical complexity of a continent urinary diversion and is the favoured approach in patients with significantly impaired renal function. The technique is considered for patients with PBPS who develop recurrent pain in the augmented bladder, continent pouch after enterocystoplasty or continent urinary diversion. Re-tubularisation of a previously used bowel segment to form a urinary conduit has been recommended [491].

Complete removal of the bladder is more likely to lead to symptom improvement compared with leaving part (subtotal cystectomy) or the whole bladder in situ [480]. In keeping with this, reports that un-resected PBPS bladders cease to induce symptoms after loss of contact with urine are limited [100,492].

Major surgery should be preceded by thorough pre-operative evaluation, with an emphasis on determining the relevant disease location and subtype. If major surgery is being considered the patient should be referred to a specialist centre experienced in managing CPPPS with a multi-disciplinary team approach.

Primary Prostate Pain Syndrome

There is no evidence for surgical management, including transurethral incision of the bladder neck, radical transurethral resection of the prostate or, in particular, radical prostatectomy in the management of chronic pain in patients with PPPS. A large Chinese RCT of circumcision combined with a triple oral therapy (ciprofloxacin, ibuprofen, tamsulosin) vs. oral therapy alone has been published for patients with PPPS (total n=774) [493]. It is hypothesised that there may be some immunological interaction via pathogenic antigen presenting cells in the foreskin with CD4+ T cells causing auto-immunity to the prostate gland. They reported an improvement in total NIH-CPSI score and subdomain scores at twelve weeks. However, despite a large cohort, the study results are questionable because of the weak theoretical background, and a potential large placebo effect lacking a sham control. In addition, no long-term effectiveness has been reported. Before having an impact on recommendations, the results of this study have to be independently confirmed and the treatment effect must persist.

Primary Testicular Pain Syndrome

Microsurgical denervation of the spermatic cord can be offered to patients with testicular pain. In a long-term follow-up study, patients who had a positive result on blocking the spermatic cord were found to have a good result following denervation [494,495].

Chronic Primary Anal and Abdominal Pain Syndrome

Chronic primary anal pain syndrome after stapled procedures, such as hemorrhoidopexy or stapled transanal rectal resection may respond to excision of the scarred staple line as shown in 21 consecutive patients with an overall improvement of pain in 85.7% of patients undergoing scar excision surgery [496]. An early scar excision before three to six months after pain onset was associated with better pain relief. Adhesiolysis is still in discussion in the pain management after laparotomy/laparoscopy for different surgical indications in the pelvis and entire abdomen. An RCT has shown, that adhesiolysis is associated with an increased risk of operative complications, and additional operations and increased health care costs as compared to laparoscopy alone [497].

Primary Urethral Pain Syndrome

There is no specific treatment that can be advised. Management should be multi-disciplinary and multi-modal [498]. Laser therapy of the trigonal region may be a specific treatment. One trial comparing two forms of laser reported good results, but did not compare with sham treatment [499]. The majority of publications on treatment of primary urethral pain syndrome have come from psychologists [500,501].

Presumed intra-abdominal adhesions

In gynaeocological patients with CPPPS and presumed adhesions, there is no consensus as to whether adhesiolysis should be performed to improve pain [501].

Extensive surgery for endometriosis is challenging and is still considered to be controversial, as there is at least one RCT showing no benefit in pain relief after the removal of early extensive endometriosis vs. sham surgery [262,502]. Increasingly treatment algorithms are being developed using a multi-disciplinary approach, although none have thus far been proven clinically [503]. In patients with adenomyosis, the only curative surgery is hysterectomy but patients can benefit from hormonal therapy and analgesics (see Section 5.2.2).

Pudendal neuralgia and surgery

Decompression of an entrapped or injured nerve is a routine approach and probably should apply to the pudendal nerve as it applies to all other nerves. There are several approaches and the approach of choice probably depends upon the nature of the pathology. The most traditional approach is transgluteal; however, a transperineal approach may be an alternative, particularly if the nerve damage is thought to be related to previous pelvic surgery [250,504-508]. Currently, there has been only one prospective RCT (transgluteal approach) [507]. This study suggests that, if the patient has had the pain for less than six years, 66% of patients will see some improvement with surgery (vs. 40% if the pain has been present for more than six years). Surgery is not the answer for all patients. On talking to patients that have undergone surgery, providing the diagnosis was clear-cut, most patients were grateful to have undergone surgery but many still have symptoms that need management.

Chronic Pelvic Pain and Prolapse/Incontinence Mesh

Removing an existing mesh is a complex procedure [509]. Each patient is approached on an individual basis depending on the type of mesh and extent of complications [510]. The complexity of surgery often involves removal of dense scar tissue, reformation of inflamed vaginal skin and surgical reconstruction of the urethra and bladder [511]. Such surgery requires specialist skills, best provided within a multi-disciplinary tertiary setting. Possible complications as a result of this surgical removal include bleeding, infection, damage to surrounding organs as well as LUTS, persistent chronic pain and recurrent SUI, which occurs after mesh removal [512].

Removal of mesh, whilst complex, does have beneficial outcomes generally, which are also durable particularly for chronic pain [513]. However, the long-term consequences after the mesh is removed still can include, not only chronic persistent pain but also autoimmune responses and complex neuropathies affecting the pelvis and lower limbs [514,515]. Some of these can be treated effectively using a multi-disciplinary pain medicine approach [516]. In other cases, the residual symptoms may require the input of an immunologist, rheumatologist or other symptom-defined specialist. The alternative to continence and prolapse mesh surgery is dependent on the clinical findings at the time. They include behavioural change, physiotherapy (for SUI and Grade I-II uterovaginal prolapse) or traditional surgical techniques. Studies have shown that over 70% who committed to physiotherapy for SUI often did not need any further intervention [517]. Many clinicians are reverting to conservative measures first, before re-considering surgery. Clinicians are also now retraining in traditional continence surgical techniques, which existed in the pre-mesh era, such as the Burch colposuspension and autologous fascial sling; as well as traditional utero-vaginal prolapse techniques such as vaginal hysterectomy, sacrospinous fixation and fascial repair of vaginal wall prolapse.

5.4. Summary of evidence and recommendations: management

5.4.1. Management of primary prostate pain syndrome

5.4.2. Management of primary bladder pain syndrome

5.4.3. Management of scrotal pain syndrome

5.4.4. Management of primary urethral pain syndrome

5.4.5. Management of gynaecological aspects of chronic pelvic pain

5.4.6. Management of primary anorectal pain syndrome

5.4.7. Management of pudendal neuralgia

5.4.8. Management of sexological aspects in chronic pelvic pain

5.4.9. Management of psychological aspects in chronic pelvic pain

5.4.10. Management of pelvic floor dysfunction

5.4.11. Management of chronic/non-acute urogenital pain by opioids