Patients referred with pain that they assign to the lower urinary tract (LUT), the pelvic floor and or the urogenital area, pose a challenge to the urologist. Commonly these patients are clustered in the interstitial cystitis/painful bladder syndrome (IC/PBS) cohort. Because IC/PBS is a syndrome, with yet undefined subtypes, a specific universal treatment for the syndrome is not available. The guidelines recommend that the syndrome is diagnosed by excluding infection or 'other identifiable causes’.(1) Most guidelines recommend cystoscopy (implicitly) to exclude urothelial neoplasm and to diagnose Hunner’s lesion(s) when present. Usually a meticulous analysis of symptoms and signs is performed and sometimes screening for psychosocial comorbidity is initiated.(2)
There is clinical evidence for overlap of the overactive bladder syndrome with the IC/PB syndrome because patients sometimes describe their (more) frequently perceived necessity to void with terms as pain, pressure or discomfort.(3) Neither of these syndromes is very specific for dysfunction of the lower urinary tract however frequent voiding is sensitive (but not very specific) for detrusor overactivity when excessive urine production is excluded. There is a lack of knowledge about how frequent ‘other identifiable causes’ for the syndrome e.g. LUT dysfunction are existing or coexisting in the patients that present with IC/PB. In a cohort of patients with IC/PBS we have evaluated how objective abnormalities of LUT function or the absence thereof, may lead to a urological phenotyping.

152 patients (female 57%) with pain referred to LUT, pelvic floor, prostat(e) or scrotum, or referred with interstitial cystitis are included in this cohort of subsequent and otherwise unselected patients. All patients were referred because of failure of the initial management to relieve the (pain)symptoms by GP, urologist and or gynecologist. For this analysis we have subdivided this cohort in clinical diagnosis -cohorts to indicate how/ where the pain was indicated by the patient. See table row heads: abd(ominal), bladder, etc.; IC was the group specifically referred (by gynecologist or urologist) with this diagnosis. Some patients had pain(ful) void(ing). Some of the patients were on chronic medication for their pain but no patient reported (former) use of ketamin.
We report the results of invasive urodynamic testing; All patients underwent invasive urodynamic testing, apart from the usual clinical assessments; no patient had any sign of urinary tract infection, anatomical abnormality or malignancy. ICS-standards regarding cystometry; transurethral fluid fill- external pressure sensors with room temperature saline medium fill rate and pressure flow in seated position were followed, however not in the patients with presumably very small capacity who were filled with a slow rate of 10-20 mL per minute, usually without informing them about the fact that (external) bladder filling was started with the aim to prevent over-focusing on sensation. Urodynamics was done without stopping the usual chronic medication, not the (uro-) specific and also not the medication for co-morbidity.

The table shows (columns) that 59% had a normal (NL) cystometric bladder filling phase, not affecting (changing) any perception of pain -in association with urodynamic filling and or voiding. Few patients had reduced compl(iance). 26% of patients in this entire group however, had detrusor overactivity. In 14% of patients the bladder filling, otherwise with normal volume adaption, provoked pain. Of all 152 patients 12 (8%) had BOO and 43 (28%) had dysfunction of voiding with straining, intermittency, inability to void and or significant difficulty to initiate voiding. 
Of the (58) patients referred with IC/PBS 15 (26%) had pain during filling that was reported to be representative, and 33 (57%) had a normal cystometry.
The second part of the table shows (of the patients with known medication status) that a significant (Chi2 .004.) number of the patients with voiding difficulties (HESIT) uses opiates, especially also tramadol and or psychoactive medication.

14% of the patients reported representative pain: 1 patient during voiding and 20 during bladder-filling. Pain assiciated with intravesical volume increment is e.g. defined in ICS 2002 standard as a sign of pain originating from detrusor muscle -bladder wall stretch. All these patients reported relief of pain after voiding. 
22 patients had a small capacity without further abnormalities (apart from early ND and SD). The large proportion of patients with DO is reported earlier and deserves specific treatment for this, and also BOO is a treatable dysfunction.
59% of patients in this cohort has a normal function of the LUT and can be categorized ‘no urological abnormalities’. Usually these patients report to feel it as a relief that nothing -dangerous or life threatening- is wrong with their bladder. These patients can possibly be referred to a professional pain team, without further urological follow up.
The number of patients with opiates and especially tramadol- related voiding dysfunction bares concern, because it seems to have caused an increase of problems, presumably because pharmacological damping of the micturition reflex in patients sensitive for this effect causes the perceived need to -excessive- straining to void and increase of -pelvic or lower abdominal- pain as a result. Objective diagnosis of dysfunction helps stratification of patients of the IC/PBS cohort and may help to de-escalate the pain syndrome.

The assessment of 'other identifiable causes’ within the IC/PB syndrome has proven to be very fruitful to allocate patients to face valid subgroups. For almost 60% of patients with pain perceived in or around the lower urinary tract the pain was not related to bladder filling or voiding and this can be used to reassure patients concerning their LUT function. Pain specialists can possibly further manage the pain, when persisting. For the cohort of patients that has DO, with sometimes very strong and reactive, and sometimes painful pevic floor muscle defence /guarding against the detrusor contractions, specific and individualized management for DO can be advised. 
The patients with pain, increasing synchronous with with bladder volume increment, deserve up-to-date IC management. 
Voiding problems in this cohort and especially a striking difficulty to initiate voiding should cause alertness regarding the chronic use of medication as pharmacogenic dysfunction is remarkably prevalent in this cohort.

Hanno PM, Erickson D, Moldwin R, Faraday MM; American Urological Association. Diagnosis and treatment of interstitial cystitis/bladder pain syndrome: AUA guideline amendment. J Urol. 2015;193(5):1545–1553.
McKernan LC, Walsh CG, Reynolds WS, Crofford LJ, Dmochowski RR, Williams DA. Psychosocial co-morbidities in Interstitial Cystitis/Bladder Pain syndrome (IC/BPS): A systematic review. Neurourol Urodyn. 2018;37(3):926–941
Reynolds WS, Mock S, Zhang X, et al. Somatic syndromes and chronic pain in women with overactive bladder. Neurourol Urodyn. 2017;36(4):1113–1118.