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, gastro-enterological 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

Abnormal central processing

Abnormal efferent signaling

Abnormal afferent signaling

Psychological, behavioural, sexual

consequences

Changes in organ function

Sensory problems

Sensitization

Regional and systemic changes: viscero/viscero/somathic hyperalgia, Trophic, autonomic, endocrine, immune responses

Referred 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

Sensitization and sprouting in chronic pain

Bladder Sphincter Urethra

Filling faze: detrusor relaxes urethra/sphincter is closed Emptying faze: detrusor contracts urethra/sphincter opens 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

T10-L2

S3-S4

Pelvic plexus

PMC

PS External urehral sphincter

Bladder

Efferent Neuroanatomy of Bladder-sphinctercomplex

nervi errigentes nervi pelvini

Bladderneck, Prostate Urethra

brain

OS

Pudendal nerve

NANC

OS

Hypogastric nerve

OS

PS

Bladder function and dysfunction

T10-L2

S3-S4

Pelvic plexus

PMC

PS

External urehral sphincter

Bladder

Afferent Neuroanatomy of Bladder-sphinctercomplex

Bladderneck

brain

Hypogastric nerve

Pudendal nerve

nervi errigentes nervi pelvini

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

Bladder function and dysfunction

T10-L2 LSt-cells

S2-S3

Pelvic plexus

Pudendal nerve

MPOA PVN, PGi

PS

penis

prostate vas vesicula, bladderneck erectile tissue

Cav

ern

osa

l ner

ves

nervi errigentes nervi pelvini

NANC

Striated muscles (S2-4)

Prevertebral ganglia

Hypogastric nerve OS

Sexual function and dysfunction

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:

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

Conclusion