1. Sandor Lovasz MD. PhD. Rózsakert Medical Center, Budapest, Hungary
Pain in the urethra
Sandor Lovasz MD. PhD.
Rózsakert Medical Center, Budapest, Hungary

2. Definition of IC/BPS Bladder pain syndrome
Suprapubic pain is related to bladder filling accompanied by other symptoms such as increased daytime and nighttime frequency.
No proven urinary infection or other obvious pathology.

3. Definition of IC/BPS Symptoms
Pain (including sensations of pressure and discomfort) is the hallmark symptom of IC/BPS. Typical IC/BPS patients report not only suprapubic pain (or pressure, discomfort) related to bladder filling but pain throughout the pelvis—in the urethra, vulva, vagina, rectum—and in extragenital locations such as the lower abdomen and back.

4. Definition of IC/BPS
Pain, pressure, discomfort or other unpleasant sensation related to the urinary bladder,
a frequent need to urinate (frequency) and/or
an urgent, overwhelming need to urinate (urgency)
Both men and women may have pain in the urethra and rectum;

5. Own data
Analysis of the anamnestic data on the 52 IC/BPS patients diagnosed in the first six months this year proved that 36/52 (70%) of the patients had expressed urethral pain with or without bladder pain.

6. Own data
The level of pain ranged from slight burning sensation to very heavy, intolerable pain.
It can be present independently of urination, causing the sitting, exercising and sexual intercourse painful or even impossible.

7. Own data
The frequently coexisting urethral pain confirms the indication of the catheter-free instillation, particularly since this is the only method providing the option of simultaneous treatment of the bladder and urethra.

8. Syndromes associated with urethral pain
Besides IC/BPS, many gynecological and urological syndromes also indicate directly or indirectly pain in the urethra: the urethral syndrome, vulvodynia, painful sexual intercourse (dyspareunia), nonbacterial chronical prostatitis, chronic pelvic pain syndrome.
The role of a leaky epithelium and potassium in the generation of bladder symptoms in interstitial cystitis/overactive bladder, urethral syndrome, prostatitis and gynecological chronic pelvic pain.
Parsons CL: 22 Dec 2010 BJU International 107(3):
All the above-mentioned syndromes unite into one primary disease process, the lower urinary dysfunction epithelium, or LUDE disease…

9. Intravesical potassium sensitivity in patients with interstitial cystitis and urethral syndrome
The PST was positive in 78% of patients with clinical IC, in 55% of patients with urethral syndrome, and in 0% of the controls…
Patients with clinical IC reported the pain as dysuria (58%), urethral/vaginal (76%), above the pubic bone (53%), lower abdomen (47%), lower back (35%), vaginal (51%), and inguinal (28%). The results were similar for patients with urethral syndrome.
Zupkas P , Parsons JK : Urology  (3):428-32

10. IC/BPS as a cause of sexual pain in women: a diagnosis to consider.
Many women with IC/PBS experience dyspareunia, often in conjunction with chronic pelvic pain.
When a woman presents with the symptoms of urinary urgency and frequency, dyspareunia, nocturia, and/or pelvic pain, IC/PBS should be part of the diagnostic evaluation.
Dyspareunia can be sufficiently explained by the side-by-side running painful urethra in the close vicinity.
Whitmore K, Siegel JF, Kelogg-Spadt S.: The Journal of Sexual Medicine 2007

11. Some of these patients show significant improvement on local GAG layer replenishment therapy, suggesting that the integrity of the GAG layer (leaky epithelium) plays an important, determining role in some of these syndromes.
Irritation, urethral and bladder pain efficiently can be treated by using adjuvant symptomatic (not causal) measures:
Irritating agents Profilactic measures
Acidic urine (pH<7) Alkalizing diet and drugs (pH 6,5-7,4)
Hyperosmotic (concentrated) urine SW>1010 Always diluted urine SW<1010
Decomposition products of drugs, antibiotics Reduce drugs, avoid antibiotics
Volatile oils, aromatic compounds of herbs IC/BPS diet and spicy foods

12. Our hypothesis: There is a GAG-layer, also in the urethra (at least partially)
GAG-layer the preventing film against irritative agents
Urethral epithelium is histologically similar to the vesical epithel
70% of IC/BPS patients have urethral pain
GAG replenishment therapy is efficient for urethral pain
The endoscopic view looks similar to the bladder
Urine can similarly irritate the urethra
Conclusion:
The GAG-layer must be present at least in the proximal part of the urethra

13. Our hypothesis (cont.)
In 70% of IC/BPS patients urethral pain is an optional part of GAG-layer affectedness
The urethral pain can be regarded as a monosymptomatic GAG-layer insufficiency
The GAG-layer lesions are focal in most cases of IC/BPS.
The GAG-layer test can successfully be used in each syndrome with urethral pain.
In cases of monofocal urethral GAG-layer insufficiency GAG-layer test can be false negative
Even at false negative GAG-layer test, local GAG-replenishment therapy significantly improve bladder capacity
The focus of the lesion can be located just on the urethra or in the vicinity of the bladder neck
In these cases Lidocain-test (catheterfree method) can proof the urethral origin of the pain
The method of choice: the GAG-layer replenishment by catheterfree instillation therapy

14. Future tasks
We suggest to set up a prospective, multicenter clinical trial to prove the hypothesis of compromised GAG-layer of the urethra in syndromes presenting urethral pain.
At the patients’ selection, GAG-layer insufficiency should be proven by the non-invasive, voiding diary based GAG-layer integrity test and the Lidocain test by using catheterfree instillation.
An ESSIC revision of guidelines and definition of IC/BPS seems to be timely.