Ragi Doggweiler

Neurourological insights into the etiology of genitourinary pain in men

PURPOSE Pelvic pain remains a challenging urological problem. Because antimicrobial therapy is often unsuccessful for relieving symptoms, it is reasonable to question whether pelvic pain is the result of microbiological versus functional pelvic disease. We analyzed clinical and urodynamic findings to evaluate the role of pelvic floor dysfunction in patients with pelvic pain. MATERIALS AND METHODS We retrospectively evaluated history, physical examination and urodynamic studies in 103 men with an average age of 47 years who presented with pelvic pain between August 1994 and August 1997. In all patients microbiological tests were negative before study entry. RESULTS The reported locations of pain were the prostate and/or perineal region in 45.6% of cases, scrotum and/or testis in 38.8%, penis in 5.8%, bladder in 5.8%, and lower abdomen and lower back in 1.9% each. Previous treatment consisted of 1 to 12 courses of antibiotics in the preceding 6 to 36 months. In 88.3% of the patients there was pathological tenderness of the striated muscle with poor to absent pelvic floor function. Urodynamics were performed in 84 cases. Cystometry was normal except for decreased compliance in 5 patients. Abnormal findings were mostly evident in the coordination of voiding and in dynamic sphincter-pelvic floor activity. Average sphincter pressure was increased to 104.9 cm. water in 72.6% of the patients, average peak urine flow was decreased to 9.9 ml. per second in 61.9% and functional urethral length was increased to greater than 35 mm. in 79.8%. Urethral profile pattern was dysfunctional, obstructed, and combined dysfunctional and obstructed in 52.4, 11.9 and 21.4% of the cases, respectively, while in 88.1% urethral sensitivity was minimally or markedly increased. CONCLUSIONS Since activity is a reflection of neural control, the apparent association of pelvic floor dysfunction with pelvic pain raises the probability of a primary or secondary central nervous system breakdown in the regulation of pelvic floor function. This hypothesis is supported by the improvement in symptoms caused by therapy aimed at modulating the pelvic floor, such as biofeedback, medication and sacral anterior root stimulation.

SIMILARITY OF DISTRIBUTIONS OF SPINAL C-FOS AND PLASMA EXTRAVASATION AFTER ACUTE CHEMICAL IRRITATION OF THE BLADDER AND THE PROSTATE

PURPOSE Persistent pain in referred areas and voiding dysfunction are characteristic symptoms of chronic abacterial prostatitis. Since referred pain from visceral organs is considered a neurological event, it appeared reasonable to hypothesize that the persistent pain associated with prostatitis might also be explained by neural mechanisms. Neurogenic plasma extravasation and c-fos expression in the spinal cord, after chemical irritation of the rat prostate, was identified as a method to investigate the neurogenic aspect of prostatic inflammation. MATERIALS AND METHODS The distribution of plasma extravasation using Evans blue dye was determined after chemical irritation of the prostate and bladder of the rat, and the distribution of dye extravasation was analyzed. c-fos expression within the spinal cord was determined immunocytochemically after chemical irritation of the prostate, bladder and superficial somatic region determined by the dye extravasation as a referred pain area (tail root). RESULTS Chemical irritation of the prostate resulted in plasma extravasation in L5 to S2 dermatomes (primarily in L6 and S1). In rats receiving bladder irritation, the distribution of plasma extravasation showed a similar pattern to that observed in animals receiving prostatic irritation. Chemical irritation of the 3 structures resulted in expression of c-fos positive cells within the lumbosacral spinal cord. With each treatment the majority of c-fos positive cells were in the L6 and S1 segments. In all 3 groups the highest percentages of c-fos positive cells were observed in deeper laminae, including the dorsal commissure and sacral parasympathetic nucleus. CONCLUSIONS Our results strongly suggest that referred pain status in inflammation of the bladder and prostate is neurogenically mediated. Based on these studies, there should be significant overlaps of nociceptive neurons within the spinal cord, which receive nociceptive inputs from pelvic soma and viscera.

Spinal NK1 receptor is upregulated after chronic bladder irritation

&NA; It has been suggested that there is a significant upregulation of the NK1 receptor (NK1R) on neurons in the dorsal spinal cord after long‐term somatic inflammation. This upregulation appears to play a significant role in central sensitization in chronic pain states. However, it is not clear whether such a change is also observed after chronic visceral (bladder) inflammation. Changes in NK1R immunoreactivity after chronic bladder irritation were investigated in order to evaluate the existence of hypersensitive states in the spinal cord after chronic bladder irritation. Experiments were performed on a total of 12 adult female Sprague–Dawley rats. In six animals, cyclophosphamide (CPA) was administered intraperitoneally for 2 weeks. Another six animals were given intraperitoneal saline injections and served as the control group. After these treatments, immunohistochemical staining for NK1Rs and substance P in rat lumbosacral spinal cord was performed. In CPA‐treated animals, NK1R‐positive areas and staining intensity within the dorsal spinal cord were significantly increased in the L5 to S2 spinal cord areas, especially in the L6 and S1 segments. In the L6 spinal segment, CPA‐treatment enhanced NK1R immunostaining in the medial and the lateral dorsal horn, as well as in the lateral laminae including the sacral parasympathetic nucleus to a lesser extent. In CPA‐treated animals, substance P staining intensity increased in the same regions in which NK1R immunoreactivity was increased. This finding probably implies the upregulation of spinal NK1R and the occurrence of central sensitization within the spinal cord after chronic visceral inflammation.

Central nervous system neurons labeled following the injection of pseudorabies virus into the rat prostate gland.

The human prostate gland plays an important role in male fertility and is involved in different functional pathologies of the male lower urinary tract (LUT). The role of the prostate in these medical disorders is mainly unknown. Traditional surgical therapeutic attempts often fail to help these patients. For years, the clinical sciences have been stagnating due to a lack of basic science knowledge. Investigations into neuroanatomy and neurophysiology are urgently needed. Therefore, the neuroanatomy of the prostate gland in an experimental setup was explored. Recent progress in neuroscience methodology allows a transneuronal tracing by using a self‐amplifying virus tracer, pseudorabies virus (PRV).

Best treatment for overactive bladder if behavioral treatment and anticholinergics fail. Onabotulinumtoxina.

ONABOTULINUMTOXINA If behavioral and anticholinergic therapies for overactive bladder (OAB) fail, treatment options are onabotulinumtoxinA (BTxA), sacral nerve stimulation (SNS) with InterStim® therapy or posterior tibial nerve stimulation. In 2000 Schurch et al published a study on the use of BTxA for the treatment of neurogenic detrusor overactivity. Soon afterwards, BTxA was also used for the treatment of idiopathic detrusor overactivity. BTxA is a protein produced by the anaerobic gram-positive bacteria clostridium botulinum. Injection of BTxA leads to temporary chemical denervation and reduced nerve cell activity in the injected tissue. Treatment with BTxA decreases detrusor pressure during the filling and voiding phases. Most published articles indicate that 100 to 300 units diluted in 10 to 30 ml of saline are injected via cystoscopy. The 10 to 30 injections are made at different sites in the bladder wall into the detrusor muscle. The minimally invasive procedure, performed with the patient under local or general anesthesia, takes 5 to 10 minutes.