title: Urethral afferent nerve activity affects the micturition reflex; implication for the relationship between stress incontinence and detrusor instability.
abstract: OBJECTIVE
  A causative relationship between stress urinary incontinence (SUI) and detrusor instability has been suspected but never proven. Many women with mixed incontinence have resolution of detrusor instability after surgical correction of SUI. We sought experimental support that stimulation of urethral afferent nerves can induce or change reflex detrusor contractions.
  
  
  METHODS
  Urethral perfusion pressure and isovolumetric bladder pressure were measured with catheters inserted through the bladder dome in urethane anesthetized female S.D. rats (250 to 300 grams; n = 12). The catheter assembly was seated securely in the bladder neck to block passage of fluid between the bladder and urethra without affecting the nerve supply to the organs. The external urethra was not catheterized. Responses were examined in the control state at a urethral saline perfusion speed of 0.075 ml. per minute. Intraurethral drugs were administered following blockade of striated sphincter activity with intravenous alpha-bungarotoxin (0.1 mg./kg.).
  
  
  RESULTS
  Stopping the urethral saline infusion caused a significant decrease in micturition frequency in approximately 50% of the animals studied (n = 12). Intraurethral lidocaine (1%) infused at 0.075 ml. per minute caused a slight decrease in urethral perfusion pressure but no change in detrusor contraction amplitude. However, intraurethral lidocaine caused a significant (45%) decrease in the bladder contraction frequency (n = 5). The micturition frequency returned to baseline 30 minutes after stopping lidocaine infusion. Intraurethral infusion of nitric oxide (NO) donors (S-nitroso-N-acetylpenicillamine [SNAP] (2 mM) or nitroprusside (1 mM) immediately decreased urethral perfusion pressure by 30 to 37% (n = 5). A 45 to 75% decrease (n = 5) in bladder contraction frequency was also seen, which was similar to that observed following lidocaine. Neither NO donor changed the amplitude of bladder contractions.
  
  
  CONCLUSIONS
  These results indicate that in the anesthetized rat activation of urethral afferents by urethral perfusion can modulate the micturition reflex. Thus in patients with stress urinary incontinence, leakage of urine into the proximal urethra may stimulate urethral afferents and facilitate voiding reflexes. This implies that stress incontinence can induce and/or increase detrusor instability. These findings have significant implications for the treatment of patients with mixed urge and stress incontinence. Correction of stress incontinence by surgery or pelvic floor exercise in patients with mixed incontinence may resolve the detrusor instability.
authors.affiliation: Department of Pharmacology, University of Pittsburgh School of Medicine, Pennsylvania, USA.
authors.forename: S Y
authors.initials: SY
authors.lastname: Jung
authors.forename: M O
authors.initials: MO
authors.lastname: Fraser
authors.forename: H
authors.initials: H
authors.lastname: Ozawa
authors.forename: O
authors.initials: O
authors.lastname: Yokoyama
authors.forename: M
authors.initials: M
authors.lastname: Yoshiyama
authors.forename: W C
authors.initials: WC
authors.lastname: De Groat
authors.forename: M B
authors.initials: MB
authors.lastname: Chancellor
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D008012:Lidocaine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012021:Reflex, Abnormal / Q000187:drug effects; D012965:Sodium Chloride / Q000494:pharmacology; D014521:Urethra / Q000187:drug effects / Q000294:innervation* / Q000503:physiopathology*; D001743:Urinary Bladder / Q000187:drug effects / Q000503:physiopathology; D014550:Urinary Incontinence, Stress / Q000503:physiopathology*; D014554:Urination / Q000502:physiology
chemical_list: D000779:Anesthetics, Local; D004791:Enzyme Inhibitors; D012965:Sodium Chloride; D008012:Lidocaine; D002211:Capsaicin; D019331:NG-Nitroarginine Methyl Ester