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      Intraprostatic injection of botulinum toxin-A in patients with refractory chronic pelvic pain syndrome: The transurethral vs. transrectal approach

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          Abstract

          Objective

          To evaluate the outcome of an intraprostatic injection of botulinum toxin-A (BTX-A) in men with refractory chronic prostatitis-associated chronic pelvic-pain syndrome (CP/CPPS) and to compare the efficacy of the transurethral and transrectal routes.

          Patients and methods

          In an uncontrolled randomised clinical trial conducted in men with refractory CP/CPPS, the patients were classified into two groups according to the route of BTX-A injection; transurethral (group 1, 28 patients) and transrectal ultrasonography-guided (group 2, 35 patients). The chronic prostatitis symptom index (CPSI), maximum urinary flow rate ( Q max) and white blood cell (WBC) count in expressed prostatic secretion (EPS) were measured before and at 3, 6 and 12 months after the injection. A significant clinical improvement (SCI, defined as a reduction of 4 points or a 25% decrease in total CPSI score) was correlated with patient age, prostate volume and symptom duration.

          Results

          In group 1, the pain and quality-of-life domain scores improved, but statistically significantly only at 6 months. The voiding score improved at all follow-up visits. In group 2 there was a significant improvement in all the CPSI domain scores at all follow-up visits, except for pain, which was insignificantly improved by 12 months. The SCI ratings in groups 1 and 2 were 36%, 79% and 57%, and 49%, 89% and 74% in group 2 at the three follow-up visits, respectively. The Q max was significantly improved in both groups during the follow-up (except at 12 months in group 1). There was a significant reduction in the mean WBC count in the EPS in patients with inflammatory prostatitis. Both prostate volume and symptom duration were significantly associated with a lower SCI rating.

          Conclusion

          BTX-A is an available treatment option for patients with refractory CP/CPPS. It is more effective in patients with a small prostate and short symptom duration. The transrectal route provided better results than the transurethral route. More prospective longer term studies are needed.

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          Most cited references35

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          EAU guidelines on chronic pelvic pain.

          These guidelines were prepared on behalf of the European Association of Urology (EAU) to help urologists assess the evidence-based management of chronic pelvic pain (CPP) and to incorporate the recommendations into their clinical practice. To revise guidelines for the diagnosis, therapy, and follow-up of CPP patients. Guidelines were compiled by a working group and based on a systematic review of current literature using the PubMed database, with important papers reviewed for the 2003 EAU guidelines as a background. A panel of experts weighted the references. The full text of the guidelines is available through the EAU Central Office and the EAU Web site (www.uroweb.org). This article is a short version of the full guidelines text and summarises the main conclusions from the guidelines on the management of CPP. A guidelines text is presented including chapters on chronic prostate pain and bladder pain syndromes, urethral pain, scrotal pain, pelvic pain in gynaecologic practice, neurogenic dysfunctions, the role of the pelvic floor and pudendal nerve, psychological factors, general treatment of CPP, nerve blocks, and neuromodulation. These guidelines have been drawn up to provide support in the management of the large and difficult group of patients suffering from CPP.
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            Intravesical botulinum toxin a administration produces analgesia against acetic acid induced bladder pain responses in rats.

            There is evidence that botulinum toxin A (BTX-A) might have analgesic properties. However, the mechanisms by which BTX-A alters pain remain largely unexplored. In the bladder afferent nerve fibers contain calcitonin gene-related peptide (CGRP). In this study we investigated the effect of intravesical BTX-A administration on CGRP immunoreactivity and bladder hyperactivity in an acetic acid induced bladder pain model in rats. Experimental and control animals were catheterized and intravesically exposed to protamine sulfate (1 ml, 10 mg/ml), followed by BTX-A (1 ml, 25 U/ml) or saline, respectively. Three or 7 days after intravesical therapy continuous cystometrograms were performed using urethane anesthesia by filling the bladder (0.08 ml per minute) with saline, followed by 0.3% acetic acid. Bladder immunohistochemistry was used to detect CGRP. The intercontraction interval (ICI) was decreased after acetic acid instillation (50.2% and 65.0%) in the control group at days 3 and 7, respectively. However, rats that received BTX-A showed a significantly decreased response (28.6% ICI decrease) to acetic acid instillation at day 7. This effect was not observed at day 3 (62.2% ICI decrease). Increased CGRP immunoreactivity was detected in the BTX treated group at day 7, which was not detected at day 3. Intravesical BTX administration blocked acetic acid induced bladder pain responses and inhibited CGRP release from afferent nerve terminals. These results support the clinical application of BTX-A for the treatment of interstitial cystitis and other types of visceral pain.
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              Botulinum toxin a has antinociceptive effects in treating interstitial cystitis.

              To present clinical evidence with botulinum toxin A (BTX-A) suggesting an antinociceptive role in patients with interstitial cystitis (IC). Intriguing evidence in a somatic pain model has suggested that BTX-A injection may have an antinociceptive effect on both acute and chronic (inflammatory) pain. Thirteen female patients (6 in the United States and 7 in Poland) with IC according to the criteria of the National Institute of Diabetes, Digestive and Kidney Disease were included. Under short general anesthesia or sedation, 100 to 200 U of Dysport (Polish patients) or Botox (U.S. patients) was injected through a cystoscope into 20 to 30 sites submucosally in the trigone and floor of the bladder. Patients were evaluated with the O'Leary-Sant validated IC questionnaire or with voiding charts and a visual analog pain scale 1 month postoperatively and at subsequent 3-month intervals. The Polish patients also underwent pretreatment and post-treatment urodynamic evaluations. Overall, 9 (69%) of 13 patients noted subjective improvement after BTX-A treatment. The Interstitial Cystitis Symptom Index and Interstitial Cystitis Problem Index mean scores improved by 71% and 69%, respectively (P <0.05). Daytime frequency, nocturia, and pain by visual analog scale decreased by 44%, 45%, and 79%, respectively (P <0.01). The first desire to void and maximal cystometric capacity increased by 58% and 57%, respectively (P <0.01). Our results suggest that BTX-A has an antinociceptive effect on bladder afferent pathways in patients with IC, producing both symptomatic and functional (ie, urodynamic) improvements.
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                Author and article information

                Contributors
                Journal
                Arab J Urol
                Arab J Urol
                Arab Journal of Urology
                Elsevier
                2090-598X
                2090-5998
                09 February 2015
                June 2015
                09 February 2015
                : 13
                : 2
                : 94-99
                Affiliations
                Urology Department, Faculty of Medicine, Tanta University, Egypt
                Author notes
                [* ]Corresponding author at: Tanta Urology Hospitals, Tanta, Egypt. m_farha1975@ 123456yahoo.com
                Article
                S2090-598X(15)00005-4
                10.1016/j.aju.2015.01.001
                4561927
                edf30aa0-c59d-4d69-9b20-9916d01b8972
                © 2015 Arab Association of Urology. Production and hosting by Elsevier B.V.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 20 July 2014
                : 28 December 2014
                : 4 January 2015
                Categories
                Original Article

                btx-a, botulinum toxin type a,cp/cpps, chronic prostatitis associated with chronic pelvic pain syndrome,nih, national institutes of health,cpsi, chronic prostatitis symptom index,qmax, maximum urinary flow rate,wbc, white blood cell,eps, expressed prostatic secretion,sci, satisfactory clinical improvement,qol, quality of life,hpf, high-power field,chronic prostatitis,pelvic pain syndrome,botulinum toxin a

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