Heat/burning sensation induced by topical application of capsaicin on perineal cutaneous area: new approach in diagnosis and treatment of chronic prostatitis/chronic pelvic pain syndrome?

OBJECTIVES: To investigate the feasibility, safety, and efficacy of perineal cutaneous application of capsaicin as a test for the diagnosis, as well as a potential therapeutic tool, in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: We recruited 22 patients (mean age 34.5 years, range 19 to 56), who had been diagnosed with CP/CPPS according to the National Institutes of Health criteria, and 6 healthy control subjects. Both groups received a topical application of 5 mL capsaicin at a concentration of 10(-5) M to the perineal body skin. The patients were asked to mark on a visual analogue scale the intensity of any heat or burning sensation. All the patients had completed a National Institutes of Health Chronic Prostatitis Symptom Index before and 1 week after the test. The scores of the two groups were compared using the Mann-Whitney U test. RESULTS: The patients with CP/CPPS reported a heat/burning sensation intensity that was statistically greater than that of the healthy controls (7.5 versus 4.3, P <0.001) and a shorter time to heat sensation onset and maximal intensity (1.5 versus 3.4 minutes, P <0.001, and 2.5 versus 7 minutes, P <0.001, respectively). Of the 22 patients, 16 reported an improvement of symptoms after 7 days and the mean National Institutes of Health Chronic Prostatitis Symptom Index score decreased from 27 to 16 (P <0.01). CONCLUSIONS: We found a statistically significant difference in the pain visual analogue scale and interval between topical application and the onset of the heat/burning sensation between patients with CP/CPPS and healthy controls. The small sample size strongly suggests the need for additional larger and more controlled studies

Intravesical infusion of resiniferatoxin by a temporary in situ drug delivery system to treat interstitial cystitis: a pilot study.

Purpose: Interstitial cystitis (IC), a syndrome characterized by motor and sensory dysfunction of the lower urinary tract, represents a diagnostic and therapeutic challenge even to highly skilled physicians. We investigated the technical feasibility and the clinical efficacy of a prolonged intravesical instillation of RTX by in situ drug delivery system in patients with IC. Material and Methods: 5 female patients (mean age 48.7 years) received a prolonged infusion of a saline solution containing 10nM of resiniferatoxin at the flow rate 25μl/h by the MiniMed 407C Infusion Pump (MiniMed Sylmar, CA, USA), connected to sovrapubic 5Fr mono Pigtail catheter, for 10 days. All patients reported frequency, nocturia and urgency, and symptoms of pelvic pain for at least six months. They showed the absence of urinary tract infection within the last three months, the absence of functional disorders of lower urinary tract and no other vesical or urethral pathology. The pre-treatment (PT) frequency/volume (FV) chart and a pain score (VAS score) were recorded. Patients were evaluated after 30 days from the end of infusion (primary end point, PEP) and after three months (secondary end point, SEP). Results: At PEP frequency reduced from 11.3±1.39 to 7.4±1.51 (p<0.01) and nocturia from 3.6±0.54 to 1.2±0.44 (p<0.01). A highly significant reduction of pain score was observed at PEP: it decreased to 2.4±0.54 from 6.7±0.83 (p<0.01). The pain score remained significantly lower at SEP (3.2±0.44 p<0.05). Nocturia was also statistically reduced at SEP (1.9±0.74) as well as frequency (8.7±1.76). No side effects were reported during the infusion as well as after the removal of the catheter. Conclusion: The present study demonstrates that the prolonged intravesical instillation of a drug by in situ drug delivery system is a feasible procedure and seems to support the efficacy of RTX in the treatment of IC patients. However further studies are necessary and mandatory to confirm our results and to define the exact action mechanism of prolonged infusion of RTX, the dosage and the treatment schedule

Dental self-care and dietary characteristics of remote-living Indigenous children

LM Jamieson, RS Bailie, M Beneforti, CR Koster, AJ Spence

Transient receptor potential vanilloid type 1 (TRPV1) expression changes from normal urothelium to transitional cell carcinoma of human bladder.

OBJECTIVE: To investigate possible changes in the expression of the transient receptor potential vanilloid type 1 (TRPV1) from normal urothelium to transitional cell carcinoma (TCC) of human bladder. METHODS: Specimens from normal bladder (n=13, mean age 62 yrs), superficial TCC (n=16, mean age 62,4 yrs) and muscle invasive bladder cancer (n=12, mean age 67 yrs), were obtained by multiple cold cup and full-thickness biopsy during open surgery. All the specimens were processed for H&E staining, immunohistochemistry and Western Blot analysis. RESULTS: In controls, the urothelium showed a labelling whose intensity was higher in the superficial cells than in the basal and club-shaped ones. In the superficial TCC, the urothelium showed a reduced labelling intensity. In the muscle invasive TCC, a very light labelling was occasionally detected in scattered superficial cells and no labelling was present in the basal cells and in those that had invaded the muscle. In controls, Western Blot analysis recognized two thick, intensely stained bands, with a molecular weight of approximately 100 and 95 kDa. In all superficial TCC there were two bands similar to control ones and in the muscle invasive two very thin, lightly stained bands. No band was detected in the patients staged as pT4. CONCLUSION: These data demonstrated a progressive loss of TRPV1 expression in the urothelium as TCC stage increased and cell differentiation was lower. Future studies will establish the importance of this loss for TCC differentiation and progression

Immunohistochemical evidence of vanilloid receptor 1 in normal human urinary bladder.

PURPOSE: Experimental and clinical evidences have shown the importance of the vanilloid receptor 1 (TRPV1) in the lower urinary tract. In humans, this receptor has been detected in nerve endings of primary sensory neurons, smooth muscle and connective tissue cells and in the rat also in the urothelium. The aim of this study is to identify, by immunohistochemistry, the cell types expressing TRPV1 in the human urinary bladder. MATERIAL AND METHODS: Specimens, obtained from normal urinary bladder by multiple biopsy and from ureter at the time of radical nefrectomy for renal cell carcinoma, were fixed and frozen. Full-thickness sections were processed for light and fluorescence microscopes. To label the TRPV1, three polyclonal antibodies were used: the anti-capsaicin receptor, the anti-VR1 (N-15) and the anti-VR1 (C-15). RESULTS: Urothelium, smooth muscle cells, mast cells and endothelium were labelled and the labelling was intracytoplasmatic. In the urothelial cells, the labelling was slightly granular. In the bladder urothelium, the superficial cells were more intensely stained than the basal and club-shaped cells. VR1-positive nerve fibers were seen running single and/or in groups in the sub-urothelium and as single varicose fibers in the muscle coat, and VR1-positive nerve endings in the urothelium. CONCLUSION: The present findings provide the evidence of the presence of TRPV1 on normal human urothelium where it could have important implications in the mechanism of action of intravesical vanilloids (capsaicin and resiniferatoxin)

Urodynamic effects of intravesical nociceptin/orphanin FQ in neurogenic detrusor overactivity: A randomized, placebo-controlled, double-blind study

Objectives. To evaluate the acute urodynamic effects of the neuropeptide nociceptin/orphanin FQ (N/OFQ) in a selected group of patients with neurogenic detrusor overactivity incontinence in a randomized, placebocontrolled, double-blind study. Methods. The study involved 14 patients who presented with neurogenic detrusor overactivity due to spinal cord injury. They were randomized to receive intravesical infusion of 1 M N/OFQ or the same dose of [desPhe1]N/OFQ (the placebo). The urodynamic parameters were the bladder capacity, volume threshold for the appearance of detrusor overactivity, and the maximal bladder pressure. The study was performed on a double-blind basis: neither the patients nor the doctors who performed the instillation could distinguish the solution containing N/OFQ from that containing [desPhe1]N/OFQ. Data are expressed as the mean SD of seven determinations. Data were statistically analyzed using the Student t test for paired or unpaired data and P 0.05 was set as the criterion for a statistically significant difference. Results. The two groups were well balanced with respect to mean age, male/female ratio, etiology of spinal cord disease, and years from the lesion. Also, the baseline mean values of bladder capacity, volume threshold for the appearance of detrusor overactivity, and maximal bladder pressure were similar. The intravesical infusion of the solution containing 1 M N/OFQ produced the following changes: bladder capacity and volume threshold for the appearance of detrusor overactivity significantly increased from 139 48 mL to 240 61 mL, and from 84 32 mL to 201 68 mL, respectively. Maximal bladder pressure decreased from 81 25 cm H2O to 66 12 cm H2O; however, this difference was not statistically significant. The intravesical infusion of the solution containing 1 M [desPhe1]N/OFQ did not produce any statistically significant modification of the urodynamic parameters. Conclusions. The results of this study confirm and extend previous results showing that N/OFQ, but not the placebo, elicits a robust acute inhibitory effect on the micturition reflex in patients with a neurogenic bladder. These findings apply nociceptin orphan peptide receptor agonists as potential novel drugs for the treatment of neurogenic urinary incontinence