title: Botulinum toxin A detrusor injections reduce postsynaptic muscular M2, M3, P2X2, and P2X3 receptors in children and adolescents who have neurogenic detrusor overactivity: a single-blind study.
abstract: OBJECTIVE
  To analyze the effect of OnabotulinumtoxinA detrusor injections on postsynaptic muscular receptors in children and adolescents with neurogenic detrusor overactivity.
  
  
  METHODS
  A bladder augmentation became necessary in 10 children and adolescents (7 males, 3 females; median age, 12 years) who had neurogenic detrusor overactivity. Seven had previously received 1 to 8 (average 3.86) OnabotulinumtoxinA detrusor injections, but their detrusor pressure could not be maintained at tolerable levels because of low-compliance bladder. The last injection session had been completed an average of 3 months (range, 1.5-3.5 months) previously. Three patients had never received that therapy and were considered controls. On the bladder dome resections, a specific receptor analysis (muscarinic M2 and M3 and purinergic P2X1, P2X2, and P2X3) was performed with confocal immunofluorescence, and nerve fiber density was analyzed with light-microscopic 3,3'-diaminobenzidine-immunohistochemical staining.
  
  
  RESULTS
  Receptor analysis showed a downregulation of all examined receptors after OnabotulinumtoxinA injections; the reductions in M2, M3, P2X2, and P2X3 receptors reached a significance level of P <.05 (Mann-Whitney test). The ratios of means (OnabotulinumtoxinA-to-control) were 0.26 for M2, 0.33 for M3, 0.35 for P2X1, 0.19 for P2X2, and 0.37 for P2X3.
  
  
  CONCLUSIONS
  OnabotulinumtoxinA detrusor injections led to significant reductions in muscular M2, M3, P2X2, and P2X3 receptors. The reductions probably affect the generated force in the urinary bladder and could contribute to the clinically observed increase in residual urine.
authors: Department of Urology, St. Hedwig Hospital, Medical School of Charité Universitätsmedizin Berlin, Germany. hschultebaukloh@hotmail.com
authors: Heinrich
authors: H
authors: Schulte-Baukloh
authors: Judith
authors: J
authors: Priefert
authors: Helmut H
authors: HH
authors: Knispel
authors: Gary W
authors: GW
authors: Lawrence
authors: Kurt
authors: K
authors: Miller
authors: Jochen
authors: J
authors: Neuhaus
mesh_terms: D000293:Adolescent; D000328:Adult; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage*; D002648:Child; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007267:Injections; D008297:Male; D009465:Neuromuscular Agents / Q000008:administration & dosage; D011446:Prospective Studies; D043585:Receptor, Muscarinic M2 / Q000096:biosynthesis* / Q000187:drug effects; D043587:Receptor, Muscarinic M3 / Q000096:biosynthesis* / Q000187:drug effects; D058476:Receptors, Purinergic P2X2 / Q000096:biosynthesis* / Q000187:drug effects; D058477:Receptors, Purinergic P2X3 / Q000096:biosynthesis* / Q000187:drug effects; D016037:Single-Blind Method; D016896:Treatment Outcome; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D014563:Urodynamics / Q000187:drug effects; D055815:Young Adult
chemical_list: D009465:Neuromuscular Agents; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D058476:Receptors, Purinergic P2X2; D058477:Receptors, Purinergic P2X3; D019274:Botulinum Toxins, Type A