Proposed Mechanism for the Efficacy of Injected Botulinum Toxin in the Treatment of Human Detrusor Overactivity

Apostolidis, Apostolos; Dasgupta, Prokar; Fowler, Clare J.

doi:10.1016/j.eururo.2005.12.010

Cited by 303 publications

(185 citation statements)

References 57 publications

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“…19 The proposed mechanisms of BoNT-A on neuronal hyperactivity are inhibition of vesicular release of excitatory neurotransmitters and neuropeptides, such as ACh, norepinephrine, adenosine triphosphate, nerve growth factor and substance P, as well as suppression of the axonal expression of the transient receptor potential vanilloid 1 channel and purinergic receptors, from the urothelium and suburothelial nerve endings. [19][20][21] In the present study, we delivered BoNT-A not into the detrusor layer, but mainly into the suburothelial layer, and achieved symptom relief in patients with refractory IC.…”

Section: Discussionmentioning

confidence: 99%

Botulinum toxin type A injection for refractory interstitial cystitis: A randomized comparative study and predictors of treatment response

et al. 2015

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Objectives: To determine whether botulinum toxin type A can represent an alternative treatment option for patients with interstitial cystitis refractory to conventional therapies. Methods: This is a single-center, prospective, open labeled, randomized comparative study. Patients with refractory interstitial cystitis were randomly divided into two groups: immediate injection (group A) or 1-month delayed injection (group B) of botulinum toxin type A after allocation. The rate of treatment response (global response assessment ≥+1: slightly improved), and changes in symptom scores and frequency volume chart variables were compared between groups 1 month after allocation. Using subjects of both groups as a single cohort, predictive factors for treatment response at 1 month post-injection and the duration of response were explored. Results: A total of 34 patients (group A n = 18, group B n = 16) were allocated. The response rate was significantly higher in group A than group B (72.2% vs 25.0%, P = 0.01). All symptom measures showed significant improvement in group A than group B. When both groups were combined as a single cohort, the response rate was 73.5% at 1 month, 58.8% at 3 months, 38.2% at 6 months and 20.6% at 12 months. The mean duration of response was 5.4 months. Multivariate analysis showed that past exposure to hydrodistension more than three times correlated with better outcomes. Conclusions: Botulinum toxin type A injection could be an alternative treatment option for patients with interstitial cystitis refractory to conventional therapies, especially for those who have received repeated hydrodistensions and transurethral fulguration.

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Section: Discussionmentioning

confidence: 99%

Botulinum toxin type A injection for refractory interstitial cystitis: A randomized comparative study and predictors of treatment response

et al. 2015

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“…72,73 In conditions of increased sensory nerve transmission after chronic inflammation and spinal cord injury, 74 increased release of ATP from the urothelium might activate the ATP receptor P2X 3 in epithelial and subepithelial layers to increase afferent nerve activity, which would account for the higher frequency of bladder contractions that are reported in both human and animal models of spinal cord injury. 74 A study in 2004 showed that BTX-A inhibits ATP release from the urothelial but not the serosal side of the bladder, suggesting that BTX-A inhibits transmitter release not only from efferent nerve endings but from sensory nerve terminals or urothelium as well.…”

Section: Effects On Acetylcholine and Atp Releasementioning

confidence: 99%

“…81 The progressive reduction in suburothelial sensory receptor levels suggests either a cascade mechanism of action involving complex inhibition at a local and central level, or a prolonged inhibitory effect of the cleaved product of SNAP-25. 72 A 2007 study showed the possible persistence of a SNAP-25 cleavage product in biopsy specimens of detrusor muscle injected with BTX-A from patients with myelomeningocele who did not respond adequately to BTX-A treatment. 82 …”

Section: Effect On P2x 3 and Capsaicin-sensitive Trpv1 Sensory Receptorsmentioning

confidence: 99%

Drug Insight: biological effects of botulinum toxin A in the lower urinary tract

et al. 2008

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SUMMARYBotulinum toxins can effectively and selectively disrupt and modulate neurotransmission in striated muscle. Recently, urologists have become interested in the use of these toxins in patients with detrusor overactivity and other urological disorders. In both striated and smooth muscle, botulinum toxin A (BTX-A) is internalized by presynaptic neurons after binding to an extracellular receptor (ganglioside and presumably synaptic vesicle protein 2C). In the neuronal cytosol, BTX-A disrupts fusion of the acetylcholine-containing vesicle with the neuronal wall by cleaving the SNAP-25 protein in the synaptic fusion complex. The net effect is selective paralysis of the low-grade contractions of the unstable detrusor, while still allowing high-grade contraction that initiates micturition. Additionally, BTX-A seems to have effects on afferent nerve activity by modulating the release of ATP in the urothelium, blocking the release of substance P, calcitonin gene-related peptide and glutamate from afferent nerves, and reducing levels of nerve growth factor. These effects on sensory feedback loops might not only help to explain the mechanism of BTX-A in relieving symptoms of overactive bladder, but also suggest a potential role for BTX-A in the relief of hyperalgesia associated with lower urinary tract disorders.

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“…Toksinas autonominius nervus (gydant hiperaktyvią šlapimo pūslę) veikia 6-9 mėnesius, skersaruožius raumenis -3-4 mėnesius [36]. Šlapimo pūslei botulino toksinas A atlieka gydomąjį vaidmenį moduliuodamas aferentinius ir referentinius impulsus, vadinasi, tiek motorines, tiek sensorines skaidulas [37].…”

Section: Gydymo Algoritmasunclassified

Šlapinimosi sutrikimai po stuburo traumų ir jų gydymas botulino toksino A endovezikinėmis injekcijomis

Černiauskienė¹,

Genytė²,

Jukna³

2017

LietChirur

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Neurogeninės kilmės šlapinimosi sutrikimai, atsiradę dėl stuburo traumos, yra aktuali problema. Sunkus stuburo pažeidimas gali sukelti padidėjusį šlapimo pūslės jautrumą, tuštinamojo pūslės raumens (detruzoriaus) hiperaktyvumą, o dėl to šlapimo nelaikymą kaupimo fazės metu. Praradus spinalinę kontrolę, kuri normaliai koordinuoja detruzoriaus susitraukimą ir šlaplės sfinkterio atsipalaidavimą šlapinantis, vystosi detruzoriaus ir sfinkterio sinerginis susitraukinėjimas arba, atvirkščiai -veziko sfinkterinė dissinergija, sukelianti fiziologiškai nenormalų šlapimo pasišalinimą. Šie pokyčiai gali pakenkti paciento gyvenimo kokybei, todėl taikomi įvairūs gydymo būdai. Pirmo pasirinkimo medikamentai yra anticholinerginiai vaistai. Jiems tapus nebeveiksmingais ir norint išvengti chirurginio gydymo, naudojamos botulino toksino A inkekcijos į šlapimo pūslės raumenį arba šlaplės sfinkterį. Botulino toksino A injekcijos -tai naujas gydymo metodas šlapinimosi sutrikimams gydyti. Jis yra veiks mingas ir sukelia mažai nepageidaujamų reiškinių, todėl ši procedūra vis dažniau atliekama klinikinėje praktikoje. Injekcijomis siekiama sumažinti slėgį pūslėje ir retinti šlapimo nelaikymo epizodų skaičių, be to, galima atlikti kartotines injekcijas. Reikšminiai žodžiai: stuburo trauma, šlapinimosi sutrikimai, botulino toksinas Neurogenic bladder in patients after spinal cord injury is a significant problem. A severe spinal cord injury might produce overactive bladder, detrusor's hyperactivity which results in urine leaking during storage phase. The loss of supraspinal control that normally coordinates detrusor contraction and sphincter relaxation during urination, can lead to segmental spinal cord reflexmediated simultaneous contractions of detrusor and sphincter or on the contrary to detrusorsphincter dyssynergia, resulting in inefficient urine voiding and high residual volume. These diseaserelated alterations may deteriorate patient's qual ity of life, therefore different approaches are being applied for patient's wellbeing. Anticholinergic medications are currently first choice for treatment of neurogenic detrusor overactivity. If anticholinergic drugs are not effective and surgery is not an option, injections of botulinum toxinA to detrusor or urethral sphincter can be chosen for lowering bladder pressure and decreasing the number of urinary incontinence episodes. Botulinum toxinA injections is a new highly efficient method with rare side effects, therefore this procedure is becoming a promising future in bladder dysfunction treatment. The botulinum toxinA treatment can be performed repeatedly.

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Proposed Mechanism for the Efficacy of Injected Botulinum Toxin in the Treatment of Human Detrusor Overactivity

Cited by 303 publications

References 57 publications

Botulinum toxin type A injection for refractory interstitial cystitis: A randomized comparative study and predictors of treatment response

Botulinum toxin type A injection for refractory interstitial cystitis: A randomized comparative study and predictors of treatment response

Drug Insight: biological effects of botulinum toxin A in the lower urinary tract

Šlapinimosi sutrikimai po stuburo traumų ir jų gydymas botulino toksino A endovezikinėmis injekcijomis

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