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

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 P2X(3) and TRPVl 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 P2X(3), TRPVl and the pan-neuronal marker PGP9.5, in comparison with controls. Results: P2X(3)-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. P2X(3)-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 P2X(3)-IR and TRPV1-IR also appeared unchanged. Conclusions: Decreased levels of sensory receptors P2X(3) and/or TRPV1 may contribute to the clinical effect of BoNT/A in detrusor overactivity.