title: Roles of opiate in lower urinary tract dysfunction associated with spinal cord injury in rats.
abstract: OBJECTIVE
  It has been reported that the opiate receptor system in the spinal cord is involved in bladder and urethral function. We determined whether U-50488 (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide), a kappa opioid receptor agonist, could decrease detrusor-sphincter dyssynergia (DSD) and, thus, improve voiding efficiency in conscious, spinal cord injured (SCI) rats.
  
  
  METHODS
  Experiments were done in female Sprague-Dawley rats in which the spinal cord was completely transected at the T6-8 level 4 weeks prior to performing cystometry while conscious and held in a restraining cage. Experiments were also performed in normal spinal cord rats. Saline was infused (0.1 ml per minute) via the cystostomy catheter into the bladder. Voiding efficiency was determined by measuring voided and residual volumes. After performing a control cystometrogram increasing doses of U-50488 (0.01, 0.1, 1 and 10 mg/kg) were administered intravenously at 1-hour intervals. The effects of nor-binaltorphimine dihydrochloride, a kappa opioid receptor antagonist, on U-50488 induced changes in voiding parameters were also examined.
  
  
  RESULTS
  A high dose of U-50488 (1 to 10 mg/kg) significantly decreased contraction amplitude and bladder capacity (p <0.01 to 0.05) in normal spinal cord and SCI rats. A low dose of U-50488 (0.01 mg/kg) increased voiding efficiency by 32.7% without decreasing bladder capacity in SCI rats. Nor-binaltorphimine hydroparameters counteracted the effect of U-50488 induced changes.
  
  
  CONCLUSIONS
  These results suggest that the kappa opioid receptor system is related to DSD caused by spinal cord injury. The kappa opioid receptor agent is believed to have therapeutic potential for treating DSD associated with SCI.
authors.affiliation: Department of Urology, University of Fukui, Matsuoka, Japan. oyoko@fmsrsa.fukui-med.ac.jp
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokoyama
authors.forename: Eiko
authors.initials: E
authors.lastname: Mita
authors.forename: Hironobu
authors.initials: H
authors.lastname: Akino
authors.forename: Kazuya
authors.initials: K
authors.lastname: Tanase
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Ishida
authors.forename: Mikio
authors.initials: M
authors.lastname: Namiki
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000818:Animals; D005260:Female; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D001743:Urinary Bladder / Q000187:drug effects / Q000503:physiopathology*
chemical_list: D011957:Receptors, Opioid; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer