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Botulinum Toxin Treatment for Pain and Inflammation in Functional Urological...
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Botulinum Toxin Treatment for Pain and Inflammation in Functional Urological Disorders

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Bacterial Toxins".

Deadline for manuscript submissions: closed (31 December 2019) | Viewed by 50358

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor

Prof. Dr. Hann-Chorng Kuo

E-Mail Website
Guest Editor
Department of Urology, Hualien Tzu Chi Hospital, Tzu Chi Medical Foundation, Buddhist Tzu Chi University, Hualien, Taiwan
Interests: botulinum neurotoxin; neurourology; urodynamics; female urology; stress urinary; incontinence; LUTS
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The botulinum toxin has been widely applied in the treatment of functional urological diseases, such as overactive bladder, neurogenic detrusor overactivity, interstitial cystitis, and chronic pelvic pain syndrome. Evidence has shown that the botulinum toxin not only affects the release of neuropeptides from motor nerve endings, but also connects sensory nerve to the central nervous system. Inflammation in the central nervous system can be reduced after botulinum toxin treatment. The scope of therapeutic targets involves detrusor overactivity; sensory disorders; bladder pain and pelvic pain; and inflammatory disorders at the bladder, prostate, and bladder outlet. Although the actual pathophysiological mechanism of the action of the botulinum toxin has not been completely demonstrated, an anti-inflammation effect might be the predominant therapeutic mechanism for functional urological disorders such as an overactive bladder, bladder hypersensitivity, interstitial cystitis, chronic pelvic pain syndrome, chronic prostatitis, and lower urinary tract symptoms/benign prostatic hyperplasia. This Special Issue of Toxins will cover the therapeutic potentials of the botulinum toxin on lower urinary tract dysfunctions, with emphasis on the mechanism of pharmacological action and clinical effects. Review articles and original articles related to the theme of this Special Issue are welcome.

Prof. Hann-Chorng Kuo
Guest Editor

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Keywords

  • Botulinum toxin
  • Functional urological disorders
  • Pain
  • Inflammation
  • Botulinum toxin treatment
  • Overactive bladder
  • Neurogenic detrusor overactivity
  • Interstitial cystitis
  • Chronic pelvic pain syndrome

Published Papers (15 papers)

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Editorial

Jump to: Research, Review

3 pages, 185 KiB  
Editorial
Botulinum Toxin Paves the Way for the Treatment of Functional Lower Urinary Tract Dysfunction
by Hann-Chorng Kuo
Toxins 2020, 12(6), 394; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12060394 - 14 Jun 2020
Cited by 4 | Viewed by 2276
Abstract
Botulinum toxin A (BoNT-A) is a potent protein that can selectively modulate neurotransmission from nerve endings, resulting in the blocking of neurotransmitter releases and causing muscular paralysis [...] Full article
(This article belongs to the Special Issue Botulinum Toxin Treatment for Pain and Inflammation in Functional Urological Disorders)

Research

Jump to: Editorial, Review

8 pages, 263 KiB  
Article
A Comparative Observational Study to Evaluate the Efficacy of Mid-Urethral Sling with Botulinum Toxin A Injection in Urinary Incontinence Patients
by Yi-Huei Chang, Po-Jen Hsiao, Huang Chi-Ping, Hsi-Chin Wu, Po-Fan Hsieh and Eric Chieh-Lung Chou
Toxins 2020, 12(6), 365; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12060365 - 02 Jun 2020
Cited by 2 | Viewed by 2474
Abstract
This study aimed to evaluate and compare the efficacy and safety of mid-urethral sling (MUS) with botulinum toxin A (BoNT-A) versus MUS only in women with mixed urinary incontinence. This was a comparative observational study, and total of 73 patients were enrolled. A [...] Read more.
This study aimed to evaluate and compare the efficacy and safety of mid-urethral sling (MUS) with botulinum toxin A (BoNT-A) versus MUS only in women with mixed urinary incontinence. This was a comparative observational study, and total of 73 patients were enrolled. A total of 38 and 35 patients received MUS only and MUS with BoNT-A injection, respectively. The efficacy outcome included change in Urinary Incontinence Outcome Scores (UIOS), change in Overactive Bladder Symptom Score (OABSS), and use of antimuscarinic agent or beta-3 agonist. Safety assessments included adverse events including urinary retention, increased postvoid residual volumes, and urinary tract infection. MUS with BoNT-A injection was insignificantly better than MUS only in urinary incontinence outcome (88% vs. 71%, respectively, p = 0.085) at week three. Among the 33 patients with detrusor overactivity (DO), patients who received BoNT-A had a higher cure rate of incontinence (88% vs. 41%, p = 0.01) and less required antimuscarinic agent or beta-3 agonist (31% vs. 94%, p < 0.001) compared to patients who did not receive BoNT-A injection. There was no significant difference in the incidences of adverse events between two groups. BoNT-A injection with MUS demonstrated efficacy and safety in the treatment of mixed urinary incontinence, specifically for women with DO. Full article
(This article belongs to the Special Issue Botulinum Toxin Treatment for Pain and Inflammation in Functional Urological Disorders)
9 pages, 239 KiB  
Article
Predictive Factors for a Satisfactory Treatment Outcome with Intravesical Botulinum Toxin A Injection in Patients with Interstitial Cystitis/Bladder Pain Syndrome
by Hsiu-Jen Wang, Wan-Ru Yu, Hueih-Ling Ong and Hann-Chorng Kuo
Toxins 2019, 11(11), 676; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins11110676 - 19 Nov 2019
Cited by 10 | Viewed by 2680
Abstract
A botulinum toxin A (BoNT-A) intravesical injection can improve the symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS). Patients with IC/BPS have different clinical characteristics, urodynamic features, and cystoscopic findings. This study assessed the treatment outcomes of a BoNT-A intravesical injection and aimed to [...] Read more.
A botulinum toxin A (BoNT-A) intravesical injection can improve the symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS). Patients with IC/BPS have different clinical characteristics, urodynamic features, and cystoscopic findings. This study assessed the treatment outcomes of a BoNT-A intravesical injection and aimed to identify the predictive factors of a satisfactory outcome. This retrospective study included IC/BPS patients treated with 100 U BoNT-A. The treatment outcomes were assessed by global response assessment (GRA) at 6 months. We classified patients according to different clinical, urodynamic, and cystoscopic characteristics and evaluated the treatment outcomes and predictive factors. A total of 238 patients were included. Among these patients, 113 (47.5%) had a satisfactory outcome (GRA ≥ 2) and 125 (52.5%) had an unsatisfactory outcome. Improvements in the IC symptom score, IC problem score, O’Leary–Sant symptom score, and visual analog scale score for pain were significantly greater in patients with a satisfactory outcome than in patients with an unsatisfactory outcome (all p = 0.000). The IC disease duration and maximal bladder capacity (MBC) were significantly different between patients with and without a satisfactory outcome. Multivariate analysis revealed that only the MBC was a predictor for a satisfactory outcome. Patients with a MBC of ≥760 mL and glomerulations of 0/1 (58.7%) or glomerulations of 2/3 (75.0%) frequently had a satisfactory outcome. We found that BoNT-A intravesical injection can effectively improve symptoms among patients with IC/BPS, with a remarkable reduction in bladder pain. A MBC of ≥760 mL is a predictive factor for a satisfactory treatment outcome. Full article
(This article belongs to the Special Issue Botulinum Toxin Treatment for Pain and Inflammation in Functional Urological Disorders)
10 pages, 275 KiB  
Article
Therapeutic Effects of Botulinum Toxin A, via Urethral Sphincter Injection on Voiding Dysfunction Due to Different Bladder and Urethral Sphincter Dysfunctions
by Yu-Khun Lee and Hann-Chorng Kuo
Toxins 2019, 11(9), 487; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins11090487 - 23 Aug 2019
Cited by 13 | Viewed by 2957
Abstract
Botulinum toxin A (BoNT-A) urethral sphincter injections have been applied in treating voiding dysfunction but the treatment outcome is not consistent. This study analyzed treatment outcomes between patients with different bladder and urethral sphincter dysfunctions. Patients with refractory voiding dysfunction due to neurogenic [...] Read more.
Botulinum toxin A (BoNT-A) urethral sphincter injections have been applied in treating voiding dysfunction but the treatment outcome is not consistent. This study analyzed treatment outcomes between patients with different bladder and urethral sphincter dysfunctions. Patients with refractory voiding dysfunction due to neurogenic or non-neurogenic etiology were treated with urethral sphincter 100 U BoNT-A injections. The treatment outcomes were assessed by a global response assessment one month after treatment. The bladder neck opening and urodynamic parameters in preoperative videourodynamic study were compared between successful and failed treatment groups. A total of 80 non-neurogenic and 75 neurogenic patients were included. A successful outcome was noted in 92 (59.4%) patients and a failed outcome in 63 (40.6%). The treatment outcome was not affected by the gender, voiding dysfunction subtype, bladder dysfunction, or sphincter dysfunction subtypes. Except an open bladder neck and higher maximum flow rate, no significant difference was noted in the other variables between groups. Non-neurogenic patients with successful outcomes had a significantly higher detrusor pressure, and patients with neurogenic voiding dysfunction with successful results had higher maximum flow rates and smaller post-void residuals than those who failed the treatment. However, increased urinary incontinence was reported in 12 (13%) patients. BoNT-A urethral sphincter injection is effective in about 60% of either neurogenic or non-neurogenic patients with voiding dysfunction. An open bladder neck during voiding and a higher maximum flow rate indicate a successful treatment outcome. Full article
(This article belongs to the Special Issue Botulinum Toxin Treatment for Pain and Inflammation in Functional Urological Disorders)

Review

Jump to: Editorial, Research

9 pages, 677 KiB  
Review
The Pharmacological Mechanism of Diabetes Mellitus-Associated Overactive Bladder and Its Treatment with Botulinum Toxin A
by Chung-Cheng Wang, Yung-Hong Jiang and Hann-Chorng Kuo
Toxins 2020, 12(3), 186; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12030186 - 16 Mar 2020
Cited by 11 | Viewed by 3577
Abstract
Diabetes mellitus (DM) is an independent risk factor for overactive bladder (OAB). The pathophysiology of DM-associated OAB is multifactorial and time-dependent. Diabetic bladder dysfunction is highly associated with diabetic complications, mainly including diabetic neuropathy and atherosclerosis. Chronic systemic inflammation and bladder urothelial inflammation [...] Read more.
Diabetes mellitus (DM) is an independent risk factor for overactive bladder (OAB). The pathophysiology of DM-associated OAB is multifactorial and time-dependent. Diabetic bladder dysfunction is highly associated with diabetic complications, mainly including diabetic neuropathy and atherosclerosis. Chronic systemic inflammation and bladder urothelial inflammation may contribute to the onset of OAB. Intravesical botulinum toxin A (BoNT-A) injection has proved to be a successful treatment for idiopathic and neurogenic OAB. BoNT-A can inhibit the efferent pathways of the bladder as well as the chronic inflammation and hypersensitivity via the afferent pathways. We conducted a review of the published literature in Pubmed using a combination of two keywords, namely “botulinum toxin A” (BoNT-A) and “overactive bladder”, with or without the additional keywords “detrusor overactivity”, “diabetes mellitus”, “inflammation”, and “urodynamic study”. We also reviewed the experience of our research teams, who have published several studies of the association between DM and OAB. Since limited data support the effectiveness and safety of BoNT-A for treating patients with DM-associated OAB, a comprehensive evaluation of diabetic complications and urodynamic study is needed before treatment. In the future, it is imperative to explore the clinical characteristics and inflammatory biomarkers of diabetes as determining predictors of the treatment efficacy. Full article
(This article belongs to the Special Issue Botulinum Toxin Treatment for Pain and Inflammation in Functional Urological Disorders)
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16 pages, 329 KiB  
Review
Therapeutic Effect of Botulinum Toxin A on Sensory Bladder Disorders—From Bench to Bedside
by Yuan-Hong Jiang, Wan-Ru Yu and Hann-Chorng Kuo
Toxins 2020, 12(3), 166; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12030166 - 09 Mar 2020
Cited by 11 | Viewed by 2932
Abstract
Bladder oversensitivity arises from several different conditions involving the bladder, bladder outlet, systemic or central nervous system diseases. Increase of the bladder sensation results from activation of the sensory receptors in the urothelial cells or suburothelial tissues. Medical treatment targeting the overactive bladder [...] Read more.
Bladder oversensitivity arises from several different conditions involving the bladder, bladder outlet, systemic or central nervous system diseases. Increase of the bladder sensation results from activation of the sensory receptors in the urothelial cells or suburothelial tissues. Medical treatment targeting the overactive bladder (OAB) or interstitial cystitis (IC) might relieve oversensitive bladder symptoms (frequency, urgency and pain) in a portion of patients, but a certain percentage of patients still need active management. Botulinum toxin A (BoNT-A) has been demonstrated to have anti-inflammatory and antinociceptive effects in bladder sensory disorders and has been shown effective in the reduction of bladder oversensitivity and the increase of functional bladder capacity. For patients with OAB, urgency and urinary incontinence improved, while in patients with IC, bladder pain could be relieved in association with reduction of bladder oversensitivity after BoNT-A intravesical injection. Histological evidence has confirmed the therapeutic mechanism and clinical efficacy of intravesical BoNT-A injection on patients with OAB or IC. Bladder oversensitivity can also be relieved with the instillation of liposome encapsulated BoNT-A or low energy show waves (LESWs), which enable the BoNT-A molecule to penetrate into the urothelium and suburothelial space without affecting the detrusor contractility. Liposome encapsulated BoNT-A or combined LESWs and BoNT-A instillation might be future treatment alternatives for bladder oversensitivity in sensory bladder disorders. Full article
(This article belongs to the Special Issue Botulinum Toxin Treatment for Pain and Inflammation in Functional Urological Disorders)
11 pages, 295 KiB  
Review
Mechanism of Action of Botulinum Toxin A in Treatment of Functional Urological Disorders
by Yu-Hua Lin, Bing-Juin Chiang and Chun-Hou Liao
Toxins 2020, 12(2), 129; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12020129 - 18 Feb 2020
Cited by 22 | Viewed by 3374
Abstract
Intravesical botulinum toxin (BoNT) injection is effective in reducing urgency and urinary incontinence. It temporarily inhibits the detrusor muscle contraction by blocking the release of acetylcholine (Ach) from the preganglionic and postganglionic nerves in the efferent nerves. BoNT-A also blocks ATP release from [...] Read more.
Intravesical botulinum toxin (BoNT) injection is effective in reducing urgency and urinary incontinence. It temporarily inhibits the detrusor muscle contraction by blocking the release of acetylcholine (Ach) from the preganglionic and postganglionic nerves in the efferent nerves. BoNT-A also blocks ATP release from purinergic efferent nerves in the detrusor muscle. In afferent nerves, BoNT-A injection markedly reduces the urothelial ATP release and increases nitric oxide (NO) release from the urothelium. BoNT-A injection in the urethra or bladder has been developed in the past few decades as the treatment method for detrusor sphincter dyssyndergia, incontinence due to neurogenic or idiopathic detrusor overactivity, sensory disorders, including bladder hypersensitivity, overactive bladder, and interstitial cystitis/chronic pelvic pain syndrome. Although the FDA only approved BoNT-A injection treatment for neurogenic detrusor overactivity and for refractory overactive bladder, emerging clinical trials have demonstrated the benefits of BoNT-A treatment in functional urological disorders. Cautious selection of patients and urodynamic evaluation for confirmation of diagnosis are crucial to maximize the successful outcomes of BoNT-A treatment. Full article
(This article belongs to the Special Issue Botulinum Toxin Treatment for Pain and Inflammation in Functional Urological Disorders)
17 pages, 2678 KiB  
Review
Comparing the Efficacy of OnabotulinumtoxinA, Sacral Neuromodulation, and Peripheral Tibial Nerve Stimulation as Third Line Treatment for the Management of Overactive Bladder Symptoms in Adults: Systematic Review and Network Meta-Analysis
by Chi-Wen Lo, Mei-Yi Wu, Stephen Shei-Dei Yang, Fu-Shan Jaw and Shang-Jen Chang
Toxins 2020, 12(2), 128; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12020128 - 18 Feb 2020
Cited by 25 | Viewed by 4862
Abstract
The American Urological Association guidelines for the management of non-neurogenic overactive bladder (OAB) recommend the use of OnabotulinumtoxinA, sacral neuromodulation (SNM), and peripheral tibial nerve stimulation (PTNS) as third line treatment options with no treatment hierarchy. The current study used network meta-analysis to [...] Read more.
The American Urological Association guidelines for the management of non-neurogenic overactive bladder (OAB) recommend the use of OnabotulinumtoxinA, sacral neuromodulation (SNM), and peripheral tibial nerve stimulation (PTNS) as third line treatment options with no treatment hierarchy. The current study used network meta-analysis to compare the efficacy of these three modalities for managing adult OAB syndrome. We performed systematic literature searches of several databases from January 1995 to September 2019 with language restricted to English. All randomized control trials that compared any dose of OnabotulinumtoxinA, SNM, and PTNS with each other or a placebo for the management of adult OAB were included in the study. Overall, 17 randomized control trials, with a follow up of 3–6 months in the predominance of trials (range 1.5–24 months), were included for analysis. For each trial outcome, the results were reported as an average number of episodes of the outcome at baseline. Compared with the placebo, all three treatments were more efficacious for the selected outcome parameters. OnabotulinumtoxinA resulted in a higher number of complications, including urinary tract infection and urine retention. Compared with OnabotulinumtoxinA and PTNS, SNM resulted in the greatest reduction in urinary incontinence episodes and voiding frequency. However, comparison of their long-term efficacy was lacking. Further studies on the long-term effectiveness of the three treatment options, with standardized questionnaires and parameters are warranted. Full article
(This article belongs to the Special Issue Botulinum Toxin Treatment for Pain and Inflammation in Functional Urological Disorders)
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18 pages, 300 KiB  
Review
Can Botulinum Toxin A Play a Role in Treatment of Chronic Pelvic Pain Syndrome in Female Patients?—Clinical and Animal Evidence
by Chin-Li Chen and En Meng
Toxins 2020, 12(2), 110; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12020110 - 10 Feb 2020
Cited by 12 | Viewed by 4143
Abstract
Chronic pelvic pain (CPP) is defined as chronic pain and inflammation in the pelvic organs for more than six months. There are wide ranges of clinical presentations, including pelvic pain, painful intercourse, irritable bowel syndrome, and pain during urinating. Chronic pelvic pain syndrome [...] Read more.
Chronic pelvic pain (CPP) is defined as chronic pain and inflammation in the pelvic organs for more than six months. There are wide ranges of clinical presentations, including pelvic pain, painful intercourse, irritable bowel syndrome, and pain during urinating. Chronic pelvic pain syndrome (CPPS) is a subdivision of CPP, and the pain syndrome may be focused within a single organ or more than one pelvic organ. As there is uncertain pathogenesis, no standard treatment is currently available for CPPS. Botulinum toxin A (BoNT-A) is a potent neurotoxin that blocks acetylcholine release to paralyze muscles. Intravesical BoNT-A injection can reduce bladder pain in patients with interstitial cystitis/bladder pain syndrome. BoNT-A injected into the pelvic floor muscles of women has also been reported to improve chronic pain syndrome. Due to the reversible effect of BoNT-A, repeated injection appears to be necessary and effective in reducing symptoms. Adverse effects of BoNT-A may worsen the preexisting conditions, including constipation, stress urinary incontinence, and fecal incontinence. This review summarizes the evidence of BoNT-A treatment for CPPS in animal studies and clinical studies regarding the therapeutic effects of BoNT-A for CPPS in female patients. Full article
(This article belongs to the Special Issue Botulinum Toxin Treatment for Pain and Inflammation in Functional Urological Disorders)
13 pages, 954 KiB  
Review
Effect of Botulinum Toxin A on Bladder Pain—Molecular Evidence and Animal Studies
by Ting-Chun Yeh, Po-Cheng Chen, Yann-Rong Su and Hann-Chorng Kuo
Toxins 2020, 12(2), 98; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12020098 - 03 Feb 2020
Cited by 10 | Viewed by 3607
Abstract
Botulinum toxin A (BTX-A) is a powerful neurotoxin with long-lasting activity that blocks muscle contractions. In addition to effects on neuromuscular junctions, BTX-A also plays a role in sensory feedback loops, suggesting the potentiality for pain relief. Although the only approved indications for [...] Read more.
Botulinum toxin A (BTX-A) is a powerful neurotoxin with long-lasting activity that blocks muscle contractions. In addition to effects on neuromuscular junctions, BTX-A also plays a role in sensory feedback loops, suggesting the potentiality for pain relief. Although the only approved indications for BTX-A in the bladder are neurogenic detrusor overactivity and refractory overactive bladder, BTX-A injections to treat bladder pain refractory to conventional therapies are also recommended. The mechanism of BTX-A activity in bladder pain is complex, with several hypotheses proposed in recent studies. Here we comprehensively reviewed properties of BTX-A in peripheral afferent and efferent nerves, the inhibition of nociceptive neurotransmitter release, the reduction of stretch-related visceral pain, and its anti-inflammatory effects on the bladder urothelium. Studies have also revealed possible effects of BTX-A in the human brain. However, further basic and clinical studies are warranted to provide solid evidence-based support in using BTX-A to treat bladder pain. Full article
(This article belongs to the Special Issue Botulinum Toxin Treatment for Pain and Inflammation in Functional Urological Disorders)
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11 pages, 1592 KiB  
Review
Therapeutic Efficacy of onabotulinumtoxinA Delivered Using Various Approaches in Sensory Bladder Disorder
by Po-Yen Chen, Wei-Chia Lee, Hung-Jen Wang and Yao-Chi Chuang
Toxins 2020, 12(2), 75; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12020075 - 23 Jan 2020
Cited by 6 | Viewed by 3176
Abstract
Cystoscopic onabotulinumtoxinA (onaBoNTA) intradetrusor injection is an efficient and durable modality for treating sensory bladder disorders. However, the inconvenience of using the cystoscopic technique and anesthesia, and the adverse effects of direct needle injection (e.g., haematuria, pain, and infections) have motivated researchers and [...] Read more.
Cystoscopic onabotulinumtoxinA (onaBoNTA) intradetrusor injection is an efficient and durable modality for treating sensory bladder disorders. However, the inconvenience of using the cystoscopic technique and anesthesia, and the adverse effects of direct needle injection (e.g., haematuria, pain, and infections) have motivated researchers and clinicians to develop diverse injection-free procedures to improve accessibility and prevent adverse effects. However, determining suitable approaches to transfer onaBoNTA, a large molecular and hydrophilic protein, through the impermeable urothelium to reach therapeutic efficacy remains an unmet medical need. Researchers have provided potential solutions in three categories: To disrupt the barrier of the urothelium (e.g., protamine sulfate), to increase the permeability of the urothelium (e.g., electromotive drug delivery and low-energy shock wave), and to create a carrier for transportation (e.g., liposomes, thermosensitive hydrogel, and hyaluronan-phosphatidylethanolamine). Thus far, most of these novel administration techniques have not been well established in their long-term efficacy; therefore, additional clinical trials are warranted to validate the therapeutic efficacy and durability of these techniques. Finally, researchers may make progress with new combinations or biomaterials to change clinical practices in the future. Full article
(This article belongs to the Special Issue Botulinum Toxin Treatment for Pain and Inflammation in Functional Urological Disorders)
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17 pages, 341 KiB  
Review
The Therapeutic Effects and Pathophysiology of Botulinum Toxin A on Voiding Dysfunction Due to Urethral Sphincter Dysfunction
by Yao-Lin Kao, Kuan-Hsun Huang, Hann-Chorng Kuo and Yin-Chien Ou
Toxins 2019, 11(12), 728; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins11120728 - 13 Dec 2019
Cited by 19 | Viewed by 3521
Abstract
Neurogenic and non-neurogenic urethral sphincter dysfunction are common causes of voiding dysfunction. Injections of botulinum toxin A (BoNT-A) into the urethral sphincter have been used to treat urethral sphincter dysfunction (USD) refractory to conventional treatment. Since its first use for patients with detrusor [...] Read more.
Neurogenic and non-neurogenic urethral sphincter dysfunction are common causes of voiding dysfunction. Injections of botulinum toxin A (BoNT-A) into the urethral sphincter have been used to treat urethral sphincter dysfunction (USD) refractory to conventional treatment. Since its first use for patients with detrusor sphincter dyssynergia in 1988, BoNT-A has been applied to various causes of USD, including dysfunctional voiding, Fowler’s syndrome, and poor relaxation of the external urethral sphincter. BoNT-A is believed to decrease urethral resistance via paralysis of the striated sphincter muscle through inhibition of acetylcholine release in the neuromuscular junction. Recovery of detrusor function in patients with detrusor underactivity combined with a hyperactive sphincter also suggested the potential neuromodulation effect of sphincteric BoNT-A injection. A large proportion of patients with different causes of USD report significant improvement in voiding after sphincteric BoNT-A injections. However, patient satisfaction might not increase with an improvement in the symptoms because of concomitant side effects including exacerbated incontinence, urinary urgency, and over-expectation. Nonetheless, in terms of efficacy and safety, BoNT-A is still a reasonable option for refractory voiding function. To date, studies focusing on urethral sphincter BoNT-A injections have been limited to the heterogeneous etiologies of USD. Further well-designed studies are thus needed. Full article
(This article belongs to the Special Issue Botulinum Toxin Treatment for Pain and Inflammation in Functional Urological Disorders)
12 pages, 249 KiB  
Review
Using Botulinum Toxin A for Treatment of Interstitial Cystitis/Bladder Pain Syndrome—Possible Pathomechanisms and Practical Issues
by Jia-Fong Jhang
Toxins 2019, 11(11), 641; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins11110641 - 04 Nov 2019
Cited by 9 | Viewed by 2688
Abstract
Treatment for patients with interstitial cystitis/bladder pain syndrome (IC/BPS) is always challenging for urologists. The main mechanism of the botulinum toxin A (BoNT-A) is inhibition of muscle contraction, but the indirect sensory modulation and anti-inflammatory effect in the bladder also play important roles [...] Read more.
Treatment for patients with interstitial cystitis/bladder pain syndrome (IC/BPS) is always challenging for urologists. The main mechanism of the botulinum toxin A (BoNT-A) is inhibition of muscle contraction, but the indirect sensory modulation and anti-inflammatory effect in the bladder also play important roles in treating patients with IC/BPS. Although current guidelines consider BoNT-A injection to be a standard treatment, some practical issues remain debatable. Most clinical evidence of this treatment comes from retrospective uncontrolled studies, and only two randomized placebo-control studies with limited patient numbers have been published. Although 100 U BoNT-A is effective for most patients with IC/BPS, the potential efficacy of 200 U BoNT-A has not been evaluated. Both trigone and diffuse body BoNT-A injections are effective and safe for IC/BPS, although comparison studies are lacking. For IC/BPS patients with Hunner’s lesion, the efficacy of BoNT-A injection remains controversial. Most patients with IC/BPS experience symptomatic relapse at six to nine months after a BoNT-A injection, although repeated injections exhibit a persistent therapeutic effect in long-term follow-up. Further randomized placebo-controlled studies with a larger number of patients are needed to support BoNT-A as standard treatment for patients with IC/BPS. Full article
(This article belongs to the Special Issue Botulinum Toxin Treatment for Pain and Inflammation in Functional Urological Disorders)
9 pages, 2426 KiB  
Review
Promise and the Pharmacological Mechanism of Botulinum Toxin A in Chronic Prostatitis Syndrome
by Chien-Hsu Chen, Pradeep Tyagi and Yao-Chi Chuang
Toxins 2019, 11(10), 586; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins11100586 - 11 Oct 2019
Cited by 5 | Viewed by 4079
Abstract
Chronic prostatitis/chronic pelvic pain syndrome (CP/ CPPS) has a negative impact on the quality of life, and its etiology still remains unknown. Although many treatment protocols have been evaluated in CP/CPPS, the outcomes have usually been disappointing. Botulinum neurotoxin A (BoNT-A), produced from [...] Read more.
Chronic prostatitis/chronic pelvic pain syndrome (CP/ CPPS) has a negative impact on the quality of life, and its etiology still remains unknown. Although many treatment protocols have been evaluated in CP/CPPS, the outcomes have usually been disappointing. Botulinum neurotoxin A (BoNT-A), produced from Clostridium botulinum, has been widely used to lower urinary tract dysfunctions such as detrusor sphincter dyssynergia, refractory overactive bladder, interstitial cystitis/bladder pain syndromes, benign prostatic hyperplasia, and CP/ CPPS in urology. Here, we review the published evidence from animal models to clinical studies for inferring the mechanism of action underlying the therapeutic efficacy of BoNT in CP/CPPS. Animal studies demonstrated that BoNT-A, a potent inhibitor of neuroexocytosis, impacts the release of sensory neurotransmitters and inflammatory mediators. This pharmacological action of BoNT-A showed promise of relieving the pain of CP/CPPS in placebo-controlled and open-label BoNT-A and has the potential to serve as an adjunct treatment for achieving better treatment outcomes in CP/CPPS patients. Full article
(This article belongs to the Special Issue Botulinum Toxin Treatment for Pain and Inflammation in Functional Urological Disorders)
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11 pages, 244 KiB  
Review
Can Botulinum Toxin A Still Have a Role in Treatment of Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia Through Inhibition of Chronic Prostatic Inflammation?
by Bing-Juin Chiang, Hann-Chorng Kuo and Chun-Hou Liao
Toxins 2019, 11(9), 547; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins11090547 - 19 Sep 2019
Cited by 9 | Viewed by 3406
Abstract
Patients with benign prostatic hyperplasia (BPH) can exhibit various lower urinary tract symptoms (LUTS) owing to bladder outlet obstruction (BOO), prostatic inflammation, and bladder response to BOO. The pathogenesis of BPH involves an imbalance of internal hormones and chronic prostatic inflammation, possibly triggered [...] Read more.
Patients with benign prostatic hyperplasia (BPH) can exhibit various lower urinary tract symptoms (LUTS) owing to bladder outlet obstruction (BOO), prostatic inflammation, and bladder response to BOO. The pathogenesis of BPH involves an imbalance of internal hormones and chronic prostatic inflammation, possibly triggered by prostatic infection, autoimmune responses, neurogenic inflammation, oxidative stress, and autonomic dysfunction. Botulinum toxin A (BoNT-A) is well recognized for its ability to block acetylcholine release at the neuromuscular junction by cleaving synaptosomal-associated proteins. Although current large clinical trials have shown no clinical benefits of BoNT-A for the management of LUTS due to BPH, BoNT-A has demonstrated beneficial effects in certain subsets of BPH patients with LUTS, especially in males with concomitant chronic prostatitis/chronic pelvic pain syndrome and smaller prostate. We conducted a review of published literature in Pubmed, using Botulinum toxin, BPH, BOO, inflammation, LUTS, and prostatitis as the key words. This article reviewed the mechanisms of BPH pathogenesis and anti-inflammatory effects of BoNT-A. The results suggested that to achieve effectiveness, the treatment of BPH with BoNT-A should be tailored according to more detailed clinical information and reliable biomarkers. Full article
(This article belongs to the Special Issue Botulinum Toxin Treatment for Pain and Inflammation in Functional Urological Disorders)
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