Skip to main content

Advertisement

SpringerLink
Log in

Intravesical instillation of botulinum toxin A: an in vivo murine study and pilot clinical trial

  • Urology – Original Paper
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Aim

The objectives of this study were to compare the urodynamic effects of botulinum toxin A (BoNT-A) delivered via intramural injection into the bladder wall to that of intravesical instillation in a rat model of detrusor overactivity and to evaluate the effects of intravesical instillation of BoNT-A in female patients with idiopathic overactive bladder.

Materials and methods

Detrusor overactivity was induced in female Wistar rats using partial bladder outflow obstruction. Animals were treated with 5 units (U) of BoNT-A via intramural bladder injection (n = 6) or intravesical instillation (n = 7). Conscious cystometrograms were performed prior to BoNT-A administration and then repeated 7 days and 2 weeks following treatment. In the subsequent pilot clinical study, 16 female patients with overactive bladder refractory to antimuscarinics were treated with 200 units of BoNT-A in 50 mL of 0.9% saline instilled using a 12-F urethral catheter. Treatment outcome was evaluated immediately prior to and 1 month after BoNT-A administration.

Results

In the preclinical study, the average intermicturition and threshold pressures, as well as the number and amplitude of non-voiding bladder contractions, decreased significantly in both instillation and injection groups. Micturition pressure decreased significantly only in the intramural injection group. In the pilot clinical study, seven patients reported improvement in symptoms. The average number of incontinence episodes was significantly reduced, and the volume at which the first non-voiding contraction was recorded increased by 52.8%.

Conclusion

The results of our urodynamic studies support the hypothesis that BoNT-A instilled into the urinary bladder affects bladder sensation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Apostolidis A, Fowler CJ (2008) The use of botulinum neurotoxin type A (BoNTA) in urology. J Neural Transm 115:593

    Article  PubMed  CAS  Google Scholar 

  2. Chancellor MB, Fowler CJ, Apostolidis A et al (2008) Drug Insight: biological effects of botulinum toxin A in the lower urinary tract. Nat Clin Pract Urol 5:319

    PubMed  CAS  Google Scholar 

  3. Chancellor MB (2009) Ten years single surgeon experience with botulinum toxin in the urinary tract; clinical observations and research discovery. Int Urol Nephrol

  4. Ghalayini IF, Al-Ghazo MA, Elnasser ZA (2009) Is efficacy of repeated intradetrusor botulinum toxin type A (Dysport((R)) injections dose dependent? Clinical and urodynamic results after four injections in patients with drug-resistant neurogenic detrusor overactivity. Int Urol Nephrol

  5. Smith CP, Vemulakonda VM, Kiss S et al (2005) Enhanced ATP release from rat bladder urothelium during chronic bladder inflammation: effect of botulinum toxin A. Neurochem Int 47:291

    Article  PubMed  CAS  Google Scholar 

  6. Smith CP, Gangitano DA, Munoz A et al (2008) Botulinum toxin type A normalizes alterations in urothelial ATP and NO release induced by chronic spinal cord injury. Neurochem Int 52:1068

    Article  PubMed  CAS  Google Scholar 

  7. Aoki KR (2001) Pharmacology and immunology of botulinum toxin serotypes. J Neurol 248(Suppl 1):3

    Article  PubMed  CAS  Google Scholar 

  8. Drake MJ (2008) Mechanisms of action of intravesical botulinum treatment in refractory detrusor overactivity. BJU Int 102(Suppl 1):11

    Article  PubMed  CAS  Google Scholar 

  9. Jankovic J, Brin MF (1997) Botulinum toxin: historical perspective and potential new indications. Muscle Nerve Suppl 6:S129

    Article  PubMed  CAS  Google Scholar 

  10. Schurch B, Stohrer M, Kramer G et al (2000) Botulinum-A toxin for treating detrusor hyperreflexia in spinal cord injured patients: a new alternative to anticholinergic drugs? Preliminary results. J Urol 164:692

    Article  PubMed  CAS  Google Scholar 

  11. Smith CP, Somogyi GT, Chancellor MB (2002) Emerging role of botulinum toxin in the treatment of neurogenic and non-neurogenic voiding dysfunction. Curr Urol Rep 3:382

    Article  PubMed  Google Scholar 

  12. Birder LA, de Groat WC (2007) Mechanisms of disease: involvement of the urothelium in bladder dysfunction. Nat Clin Pract Urol 4:46

    Article  PubMed  CAS  Google Scholar 

  13. Wiseman OJ, Brady CM, Hussain IF et al (2002) The ultrastructure of bladder lamina propria nerves in healthy subjects and patients with detrusor hyperreflexia. J Urol 168:2040

    Article  PubMed  Google Scholar 

  14. Apodaca G, Kiss S, Ruiz W et al (2003) Disruption of bladder epithelium barrier function after spinal cord injury. Am J Physiol Renal Physiol 284:F966

    PubMed  CAS  Google Scholar 

  15. Zvara P, Kliment J Jr, DeRoss AL et al (2002) Differential expression of bladder neurotrophic factor mRNA in male and female rats after bladder outflow obstruction. J Urol 168:2682

    Article  PubMed  CAS  Google Scholar 

  16. Tan TL, Bergmann MA, Griffiths D et al (2004) Stop test or pressure-flow study? Measuring detrusor contractility in older females. Neurourol Urodyn 23:184

    Article  PubMed  Google Scholar 

  17. Smith CP, Chancellor MB (2004) Emerging role of botulinum toxin in the management of voiding dysfunction. J Urol 171:2128

    Article  PubMed  CAS  Google Scholar 

  18. Brendler CB, Radebaugh LC, Mohler JL (1989) Topical oxybutynin chloride for relaxation of dysfunctional bladders. J Urol 141:1350

    PubMed  CAS  Google Scholar 

  19. Fowler CJ, Jewkes D, McDonald WI et al (1992) Intravesical capsaicin for neurogenic bladder dysfunction. Lancet 339:1239

    Article  PubMed  CAS  Google Scholar 

  20. Chancellor MB, de Groat WC (1999) Intravesical capsaicin and resiniferatoxin therapy: spicing up the ways to treat the overactive bladder. J Urol 162:3

    Article  PubMed  CAS  Google Scholar 

  21. De Ridder D, Chandiramani V, Dasgupta P et al (1997) Intravesical capsaicin as a treatment for refractory detrusor hyperreflexia: a dual center study with long-term followup. J Urol 158:2087

    Article  PubMed  Google Scholar 

  22. Szallasi A, Fowler CJ (2002) After a decade of intravesical vanilloid therapy: still more questions than answers. Lancet Neurol 1:167

    Article  PubMed  CAS  Google Scholar 

  23. Smith CP, Radziszewski P, Borkowski A et al (2004) Botulinum toxin a has antinociceptive effects in treating interstitial cystitis. Urology 64:871

    Article  PubMed  Google Scholar 

  24. Giannantoni A, Costantini E, Di Stasi SM et al (2006) Botulinum A toxin intravesical injections in the treatment of painful bladder syndrome: a pilot study. Eur Urol 49:704

    Article  PubMed  CAS  Google Scholar 

  25. Chuang YC, Yoshimura N, Huang CC et al (2004) Intravesical botulinum toxin a administration produces analgesia against acetic acid induced bladder pain responses in rats. J Urol 172:1529

    Article  PubMed  CAS  Google Scholar 

  26. Atiemo H, Wynes J, Chuo J et al (2005) Effect of botulinum toxin on detrusor overactivity induced by intravesical adenosine triphosphate and capsaicin in a rat model. Urology 65:622

    Article  PubMed  Google Scholar 

  27. Apostolidis A, Popat R, Yiangou Y et al (2005) Decreased sensory receptors P2X3 and TRPV1 in suburothelial nerve fibers following intradetrusor injections of botulinum toxin for human detrusor overactivity. J Urol 174:977

    Article  PubMed  CAS  Google Scholar 

  28. Birder LA, Kanai AJ, de Groat WC et al (2001) Vanilloid receptor expression suggests a sensory role for urinary bladder epithelial cells. Proc Natl Acad Sci USA 98:13396

    Article  PubMed  CAS  Google Scholar 

  29. Khera M, Somogyi GT, Salas NA et al (2005) In vivo effects of botulinum toxin A on visceral sensory function in chronic spinal cord-injured rats. Urology 66:208

    Article  PubMed  Google Scholar 

  30. Petrou SP, Parker AS, Crook JE et al (2009) Botulinum a toxin/dimethyl sulfoxide bladder instillations for women with refractory idiopathic detrusor overactivity: a phase 1/2 study. Mayo Clin Proc 84:702

    Article  PubMed  CAS  Google Scholar 

  31. Chuang YC, Tyagi P, Huang CC et al (2009) Urodynamic and immunohistochemical evaluation of intravesical botulinum toxin A delivery using liposomes. J Urol 182:786

    Article  PubMed  CAS  Google Scholar 

  32. Sahai A, Sangster P, Kalsi V et al (2009) Assessment of urodynamic and detrusor contractility variables in patients with overactive bladder syndrome treated with botulinum toxin-A: is incomplete bladder emptying predictable? BJU Int 103:630

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Urology, University Hospital Ostrava, Ostrava, Czech Republic

    Jan Krhut

  2. Department of Surgery, Division of Urology, University of Vermont, D319 Given Building, 89 Beaumont Avenue, Burlington, VT, 05405, USA

    Peter Zvara

Authors
  1. Jan Krhut
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter Zvara
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter Zvara.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Krhut, J., Zvara, P. Intravesical instillation of botulinum toxin A: an in vivo murine study and pilot clinical trial. Int Urol Nephrol 43, 337–343 (2011). https://doi.org/10.1007/s11255-010-9790-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-010-9790-z

Keywords

Search

Navigation