title: Onabotulinumtoxin-A intradetrusorial injections modulate bladder expression of NGF, TrkA, p75 and TRPV1 in patients with detrusor overactivity.
abstract: How onabotulinumtoxinA (onab/A) injected in the detrusor muscle improves detrusor overactivity (DO) is still a matter of debate. Nerve growth factor (NGF) seems to play a role in determining urgency and DO. Recent studies showed that NGF decreases in patients with DO who respond to onab/A treatment. We investigated onab/A-induced changes on gene expression of NGF, TRPV1, TrkA and p75 in bladder wall tissue of patients affected by neurogenic and idiopathic DO. Twenty-five patients (18 with neurogenic DO and 7 with idiopathic DO) received onab/A injections into the detrusor muscle. Urodynamic studies and cystoscopies with sampling of the bladder wall were performed before and 1 month after onab/A injections. Onab/A-induced changes in urodynamic variables (first volume and maximum pressure of uninhibited detrusor contractions and maximum cystometric capacity) and NGF, TRPV1, TRKA, p75 gene expression by means of quantitative Real Time-Polymerase Chain Reaction. NGF protein levels were assessed in tissue homogenates by enzyme-linked immunosorbent assay. Onab/A significantly improved urodynamic findings (as shown by the increase in maximum cystometric capacity), decreased the bladder tissue levels of NGF protein and significantly increased NGF, TrkA, p75 and TRPV1 gene expression independently from the etiology of DO. No significant correlation has been found between NGF down-regulation and the increase in MCC. Correlations between NGF gene expression and NGF receptors' gene expression were influenced by onab/A dosages. In the short time follow-up, onab/A decreases NGF protein levels and increases NGF and associated receptors' gene expression possibly by inhibiting NGF release. Further studies with longer follow-up will clarify time course of onab/A-induced modifications in NGF expression.
authors.affiliation: Department of Urology and Andrology, University of Perugia, Perugia, Italy. agianton@libero.it
authors.forename: Antonella
authors.initials: A
authors.lastname: Giannantoni
authors.forename: Antonella
authors.initials: A
authors.lastname: Conte
authors.forename: Valerio
authors.initials: V
authors.lastname: Farfariello
authors.forename: Silvia
authors.initials: S
authors.lastname: Proietti
authors.forename: Alberto
authors.initials: A
authors.lastname: Vianello
authors.forename: Vincenza
authors.initials: V
authors.lastname: Nardicchi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Santoni
authors.forename: Consuelo
authors.initials: C
authors.lastname: Amantini
mesh_terms: D000328:Adult; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D020917:Receptor, trkA / Q000235:genetics; D017475:Receptors, Nerve Growth Factor / Q000235:genetics; D050916:TRPV Cation Channels; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism; D053201:Urinary Bladder, Overactive / Q000235:genetics*
chemical_list: C502240:NGF protein, human; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D019274:Botulinum Toxins, Type A