Neuroanatomy, Neurophysiology and Clinical Presentation of Visceral Urological Pain Prof Dr K. Everaert Functional urology Department of Urology Ghent University Hospital Gent, Belgium Chronic pelvic pain Definition: chronic pain in the pelvis without obvious local pathology that can explain the pain, mostly associated with sexual, urological, gynaecological, gastroenterological and emotional symptoms. Prevalence: estimated around 10% Fenotype: generalized pain (CPP-syndrome) versus localized pain (chronic prostatitis, orchialgia, interstitial cystitis,…. Pain is accompanied by a lot of dysfunction and loss in QOL. Sensitization, sprouting, activation sympathetic Sensitization Abnormal afferent signaling Abnormal efferent signaling Abnormal central processing Sensory problems Changes in organ function Psychological, behavioural, sexual consequences Regional and systemic changes: viscero/viscero/somathic hyperalgia, Trophic, autonomic, endocrine, immune responses Referred pain Sensitization and sprouting in chronic pain Complex regional pain syndromes : Starts from somatic or visceral or neuropathic or dysfunctional pain  Neuropathic-like pain accompanied by muscle spasm (pain cycle, pelvic floor dysfunction) and vasodilatation and vasoconstriction  Neurogenic inflammation  Important dysfunction Bladder function and dysfunction Filling faze: detrusor relaxes urethra/sphincter is closed Bladder Emptying faze: detrusor contracts urethra/sphincter opens Sphincter Urethra When 1 aspect is dysfunctional, lower urinary tract symptoms occur (LUTS) : - incontinence, urgency, frequency, nocturia - slow stream, difficulties to start postmicturition dribbling Bladder function and dysfunction PMC Efferent Neuroanatomy of Bladder-sphinctercomplex OS Hypogastric nerve PS External urehral sphincter T10-L2 OS Bladder Bladderneck, Prostate Urethra brain OS NANC Pelvic plexus nervi errigentes nervi pelvini Pudendal nerve PS S3-S4 Bladder function and dysfunction brain PMC Afferent Neuroanatomy of Bladder-sphinctercomplex Hypogastric nerve T10-L2 Bladder Bladderneck External urehral sphincter Pelvic plexus PS nervi errigentes nervi pelvini Pudendal nerve S3-S4 Bladder function and dysfunction Afferents of the Lower Urinary Tract Bladder function and dysfunction AFFERENTS : interstitial cells (Cajal like cells) • Superficial network of IC: the sensing network (valinoied receptors), connect urothelium – nerve fibers – IC cells off detrusor - detrusor • Detrusor network of IC: modulators of autonomous activity, rather then pacemakers - Purinergic P2Y receptor - Cholinergic M2-3 receptors - Vallinoied receptors - NGF Van Der Aa Fr, 2007 Bladder function and dysfunction AFFERENTS FOR URGE and PAIN Steers W 2002 Sexual function and dysfunction prostate vas vesicula, bladderneck erectile tissue penis Cavernosal nerves Prevertebral ganglia OS MPOA PVN, PGi T10-L2 LSt-cells Hypogastric nerve Pelvic plexus NANC PS nervi errigentes nervi pelvini Pudendal nerve Striated muscles (S2-4) S2-S3 Chronic Bladder Pain Syndrome Definition, prevalence: Also known as interstitial cystitis Often starts with a urinary tract infection, pelvic trauma, surgery Has a phasic evolution but sometimes progressive Symptoms are these of cystitis and an overactive bladder, but due to sphincter spasms also emptying phaze symptoms are present Inflammation of the bladder wall leads to damage to the GAG-layer of the bladder Both the dysfunctions as the GAG-layer damage provoke more UTI Chronic inflammation ends in scarring and shrinkage of the bladder ending in an extremely painful bladder with invalidating frequency and nocturia. Chronic Bladder Pain Syndrome Diagnosis: Mainly clinical: pain in relation to filling of the bladder with frequency and nocturia + micturition diary + urine analysis + uroflowmetry and residual urine are needed. Urodynamics, cystoscopy, bladder biopsy and potassium instillation test are optional Chronic Bladder Pain Syndrome Therapy level 1: 1) Early pain therapy: amitryptiline, nortryptiline, duloxetine…. tramadol gabapentine, pregabaline 2) Treat filling faze symptoms - bladdertraining - anticholinergics, beta-3-agonists 3) Treat emptying faze symptoms - pelvic floor rehabilitation - alpha-blocking agents - intermittent catheterization Chronic Bladder Pain Syndrome Therapy level 2: 1) Bladder instillations with: - DMSO (anti-inflammatory) - GAG-layer replacers (Heparin, Uracyst, Cystistat, Iauril…) 2) Bladder injections with onabotulinumtoxinA 3) Treat filling faze symptoms - onabotulinumtoxinA - sacral neuromodulation 4) Treat emptying faze symptoms - sacral neuromodulation Therapy level 3: When these fail: partial or radical cystectomy with enterocystoplasty, neobladder or urinary diversion Chronic Prostatitis/Prostatodynia Definition: Chronic pain syndrome localized to the prostate, also called abacterial chronic prostatitis or prostatodynia Symptoms of prostatitis with negative culture (3-glass specimen test) sometimes leucocytes, sometimes only inflammatory markers like interleukines Pain often extends to obturator region, testes, inguinal region and flanks Chronic Prostatitis/Prostatodynia Diagnosis: Mainly clinical: pain in the prostate with frequency and nocturia + micturition diary + urine analysis (3-glass specimen test) + uroflowmetry and residual urine are needed. Urodynamics, cystoscopy , sperm analysis are optional Chronic Prostatitis/Prostatodynia Therapy level 1: 1) Early pain therapy: amitryptiline, nortryptiline, duloxetine…. tramadol gabapentine, pregabaline 2) Treat filling faze symptoms - bladdertraining - anticholinergics, beta-3-agonists 3) Treat emptying faze symptoms - pelvic floor rehabilitation - alpha-blocking agents - intermittent catheterization Chronic Prostatitis/Prostatodynia Therapy level 2: Many suggestion, no proof of efficacy: thermotherapy, lasertherapy, TURp, onabotulinumtoxin, sacral neuromodulation Therapy level 3: Radical prostatectomy: no proof of efficacy, unethical without multidisciplinary approach, high complication rates Chronic Orchialgia Definition and prevalence: Chronic pain localized to the testis and existing for at least 3 months and disturbing for the daily life activities. Many men have some discomfort (they realize having a testis with certain movements) which is not taken in account here. Prevalence estimated at 1% In 15-20% pain starts with surgery like inguinal hernia repair, vasectomy or epidydymitis Chronic Orchialgia Diagnosis: Mainly clinical Urine analysis, sperm count and bacteriology, ultrasound, urofllowmetry with residual are suggested Sometimes MRI /Ct-scan of the pelvis, transrectal ultrasound, cystoscopy, neurological evaluation,… but rarely leads to a diagnosis and are only advised when abnormalities are suggested by the first level of diagnostics. Chronic Orchialgia Therapy: Conclusion  Understand pelvic organ innervation and dysfunctions  Use painkillers early and in sufficient dose  Use different painkillers by understanding their differences in working mechanisms  Treat dysfunction and pain early, avoid sensitization  Collaboration with pain clinic when urologist is not comfortable with installing pain therapy  Destructive surgery only in highly invalidating cases, collaboration with pain clinic is helpful in patient selection