Decreased sensory receptors P2X3 and TRPV1 in suburothelial nerve fibers following intradetrusor injections of botulinum toxin for human detrusor overactivity

J Urol. 2005 Sep;174(3):977-82; discussion 982-3. doi: 10.1097/01.ju.0000169481.42259.54.


Purpose: Botulinum neurotoxin type A (BoNT/A) is effective in the treatment of intractable detrusor overactivity (DO). In addition to its known inhibitory effect on presynaptic release of acetylcholine by motor terminals, there is increasing evidence that BoNT/A may affect sensory fibers. We investigated a possible effect of BoNT/A on human bladder afferent mechanisms by studying the sensory receptors P2X3 and TRPV1 in biopsies from patients with neurogenic or idiopathic DO.

Materials and methods: A total of 38 patients (22 with neurogenic DO, 16 with idiopathic DO) with intractable DO were treated with intradetrusor BoNT/A, and bladder biopsies were taken at 4 and 16 weeks. Urodynamics and voiding diary were also recorded. Specimens were studied immunohistochemically for P2X3, TRPV1 and the pan-neuronal marker PGP9.5, in comparison with controls.

Results: P2X3-immunoreactive and TRPV1-immunoreactive (-IR) fibers were decreased at 4 weeks after BoNT/A, and more significantly at 16 weeks (paired t test p=0.0004 and p=0.0008, respectively), when significant improvements were observed in clinical and urodynamic parameters. P2X3-IR fiber decrease was significantly correlated with reduction of urgency episodes at 4 and 16 weeks (p=0.0013 at 4 weeks and p=0.02 at 16 weeks), but not maximum cystometric capacity or detrusor pressures. TRPV1-IR fiber decrease showed a similar trend. PGP9.5-IR suburothelial fibers remained unchanged after treatment at both followups (p=0.85 and p=0.21 at 4 and 16 weeks, respectively). Urothelial cell P2X3-IR and TRPV1-IR also appeared unchanged.

Conclusions: Decreased levels of sensory receptors P2X3 and/or TRPV1 may contribute to the clinical effect of BoNT/A in detrusor overactivity.

MeSH terms

  • Adult
  • Afferent Pathways / drug effects
  • Aged
  • Biopsy
  • Botulinum Toxins, Type A / administration & dosage*
  • Botulinum Toxins, Type A / adverse effects
  • Cystoscopy
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Injections, Intramuscular
  • Ion Channels / drug effects*
  • Male
  • Middle Aged
  • Muscle Hypertonia / drug therapy*
  • Muscle Hypertonia / pathology
  • Nerve Fibers / drug effects*
  • Nerve Fibers / pathology
  • Nerve Fibers, Unmyelinated / drug effects
  • Nerve Fibers, Unmyelinated / pathology
  • Neuromuscular Agents / administration & dosage*
  • Neuromuscular Agents / adverse effects
  • Receptors, Purinergic P2 / drug effects*
  • Receptors, Purinergic P2X3
  • Sensitivity and Specificity
  • Sensory Receptor Cells / drug effects*
  • Synaptic Transmission / drug effects*
  • TRPV Cation Channels
  • Treatment Outcome
  • Urinary Bladder / innervation*
  • Urinary Bladder / pathology
  • Urinary Bladder, Neurogenic / drug therapy*
  • Urinary Bladder, Neurogenic / pathology
  • Urinary Incontinence / drug therapy*
  • Urinary Incontinence / pathology
  • Urodynamics / drug effects
  • Urothelium / innervation
  • Urothelium / pathology


  • Ion Channels
  • Neuromuscular Agents
  • P2RX3 protein, human
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X3
  • TRPV Cation Channels
  • TRPV1 protein, human
  • Botulinum Toxins, Type A