title: Central inhibitory effect of intravesically applied botulinum toxin A in chronic spinal cord injury.
abstract: OBJECTIVE
  We evaluated a putative central inhibitory effect of intravesical botulinum toxin A (BoNT-A) on the activity of lumbosacral spinal neurons in a chronic spinal cord injury (SCI) model of bladder overactivity.
  
  
  METHODS
  Female Sprague-Dawley rats underwent T8 spinal cord transection. Four weeks later, once overactive neuropathic detrusor pathways had developed, the animals underwent intravesical instillation with either saline (1 ml) or BoNT-A (Botox®, 20 U/1 ml) for 1 hr. Two days later, the rats then completed a cystometric evaluation prior to spinal cord harvest. Sections from the L4-S1 spinal cord segments were examined for the total number of c-fos immunoreactive cells.
  
  
  RESULTS
  Comparison of the saline and BoNT-A treated groups showed a significant decrease in L6 (i.e., 67%, P < 0.001) and S1 (i.e., 47%, P < 0.01) c-fos expression (43%) in BoNT-A treated rats compared to saline controls. Cystometrogram studies revealed that the frequency of non-voiding bladder contractions was reduced by 73% (P < 0.05) in BoNT-A compared to saline treated rats. No change in the frequency of voiding bladder contractions or amplitude of bladder contraction was observed between the saline and BoNT-A treated groups.
  
  
  CONCLUSIONS
  In a SCI model of bladder overactivity, intravesical BoNT-A significantly inhibits the response of bladder afferent activated lumbosacral neurons without significantly impairing efferent bladder function.
authors.affiliation: Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Munoz
authors.forename: George T
authors.initials: GT
authors.lastname: Somogyi
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Boone
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Smith
mesh_terms: D000283:Administration, Intravesical; D000818:Animals; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage*; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D009119:Muscle Contraction / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects*; D009465:Neuromuscular Agents / Q000008:administration & dosage*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D013127:Spinal Nerves / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors; D001743:Urinary Bladder / Q000294:innervation*; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D014563:Urodynamics / Q000187:drug effects
chemical_list: D009465:Neuromuscular Agents; D016760:Proto-Oncogene Proteins c-fos; D019274:Botulinum Toxins, Type A