title: A bladder-cooling reflex in the anaesthetised guinea-pig: a model of the positive clinical ice-water test.
abstract: BACKGROUND
  In patients with detrusor hyperreflexia, intravesical instillation of ice-cold water results in the development of involuntary bladder contractions at volumes less than normal cystometric capacity. This is referred to as a positive ice-water test (+IWT) and can be reversed by vanilloid receptor agonists and potentiated by menthol. The present study was designed to investigate the existence of an analogous cooling reflex in the guinea-pig bladder that could be used as a small animal model in order to test the effects of drugs on the reflex.
  
  
  METHODS
  Bladder pressure and external urethral sphincter electromyogram (EUS EMG) were recorded in alpha-chloralose/urethane anaesthetised guinea-pigs during rapid infusion of cold or warm saline into the bladder with or without prior intravesical exposure to menthol or resiniferatoxin (RTX).
  
  
  RESULTS
  The mean control micturition threshold volume (TV) of 2.58 ml at 38 degrees C was reduced to 1.52 ml in response to saline infusion at 3 degrees C (P=0.001). The cold-induced reduction in TV was reproducible during several subsequent repeat infusions at 38 degrees C and 3 degrees C and was accompanied by decreases in bladder voiding pressure. The duration of the micturition reflex was markedly increased following cold compared with warm saline infusion (mean 24.5 s at 3 degrees C, 10.2 s at 38 degrees C, P=0.001) and was associated with oscillations in bladder pressure and concomitant bursting activity in the EUS EMG. During step-wise decreases in infusate temperature from 38 degrees C to 23 degrees C, 15 degrees C, 7 degrees C and 3 degrees C, the threshold infusate temperature to elicit a significant reduction in TV was 15 degrees C. The reduction in TV at 3 degrees C was potentiated by intravesical infusion of 0.6 mM menthol whilst intravesical infusion of 500 nM RTX reversed the reduction in TV at 3 degrees C.
  
  
  CONCLUSIONS
  These data suggest that a bladder-cooling reflex is present in the anaesthetised guinea-pig and represents a useful small animal model of the clinical +IWT.
authors.affiliation: Department of Discovery Biology, i.p.c. 664, Pfizer Global R&D, Sandwich, Kent CT13 9NJ, UK. jennifer.gardiner@pfizer.com
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Gardiner
authors.forename: Gordon
authors.initials: G
authors.lastname: McMurray
authors.forename: Simon
authors.initials: S
authors.lastname: Westbrook
mesh_terms: D000758:Anesthesia; D000818:Animals; D003080:Cold Temperature; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology; D004576:Electromyography / Q000379:methods; D005260:Female; D006168:Guinea Pigs; D008610:Menthol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D012018:Reflex / Q000502:physiology*; D012965:Sodium Chloride / Q000008:administration & dosage / Q000494:pharmacology; D013696:Temperature; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D014554:Urination / Q000187:drug effects / Q000502:physiology; D014867:Water
chemical_list: D004224:Diterpenes; D014867:Water; D008610:Menthol; D012965:Sodium Chloride; C024353:resiniferatoxin