Onabotulinumtoxina Intradetrusorial Injections and NGF Expression
Condition: Overactive Detrusor; Detrusor Hyperreflexia of Bladder
MeSH terms: Reflex, Abnormal; Urinary Bladder, Overactive
Study type: Observational

Summary: 
      In the last years, botulinum toxin type A (onab/A) has been increasingly used as a treatment
      option for overactive bladder symptoms in patients affected by either neurogenic and
      idiopathic detrusor overactivity (DO). How onab/A injected into the detrusor muscle improves
      overactive bladder symptoms in neurologic patients has been only partially investigated.Some
      evidence suggested that the neurotoxin probably reduces detrusor muscle contraction blocking
      detrusor muscle cholinergic innervation. However, recent experimental observations indicated
      that onab/A determines more complex effects on bladder activity acting on afferent
      innervations as well as on the efferent one. Only few experimental studies have investigated
      the activity of onab/A on bladder afferent nervous transmission. Experimental studies in
      animals showed that Nerve Growth Factor (NGF) elicits increased sensation, urgency and DO.
      Although there are some evidence on the ability of onab/A to improve DO and to reduce bladder
      and urinary content of NGF, how onab/A influences NGF expression and the expression of TrKa,
      p75 and TRPV1 receptors is still unclear. The hypothesis is that onab/A reduces NGF bladder
      tissue levels and in the same time it modulates the gene expression of NGF associated
      receptors (TrkA, p75 and TRPV1).
    

Detailed description: 
      NGF has been suggested to modulate neurotransmitters' release, induces synaptic
      reorganization and influences neuronal excitability acting on Trk/A and p75 associated
      receptors. Moreover, recent observations indicated that NGF-induced DO and noxious input
      depend on the interaction of NGF with TRPV1, that is over-expressed in overactive bladders
      and interstitial cystitis/painful bladder syndrome. From a clinical point of view, a decrease
      in urinary NGF levels has been detected in patients with DO treated with onab/A. Although
      there are some evidence on the ability of onab/A to improve DO and to reduce bladder and
      urinary content of NGF, how onab/A influences NGF expression and the expression of TrKa, p75
      and TRPV1 receptors is still unclear.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        We consecutively enrolled 18 patients with neurogenic DO (8 patients with spinal cord
        injury: 7 men and 1 women, mean age: 46±2 yrs, disease duration 6.25±1 yrs; 10 patients
        with suprapontine bilateral lesions: 4 men and 6 women, mean age: 55±4 yrs, disease
        duration 6.6±1.49 yrs ) and 7 with idiopathic DO (3 men and 4 female, mean age: 53±5 yrs,
        disease duration 7.1±1.53 yrs). All the patients had overactive bladder (OAB) symptoms and
        DO refractory to conventional anticholinergics (at least 3 antimuscarinic agents --
        tolterodine, oxybutynin and solifenacin -- each taken for at least 1 month).
        Anticholinergics were discontinued one month before entry into the study.
      
Biospecimen description: 
      Bladder biopsy specimens obtained from the postero-lateral wall of the bladder with cold cup
      resection. Deep bladder wall biopsy including urothelium and smooth muscle were performed. No
      biopsies were taken from the bladder neck or the trigone.
    
Keywords: idiopathic detrusor overactivity; neurogenic dysfunction; onabotulinumtoxinA