title: Combination of foot stimulation and tramadol treatment reverses irritation induced bladder overactivity in cats.
abstract: OBJECTIVE
  We determined whether transcutaneous electrical foot stimulation combined with a low dose of tramadol (Sigma-Aldrich®) could completely suppress bladder overactivity.
  
  
  METHODS
  Repeat cystometrograms were performed in 18 α-chloralose anesthetized cats by infusing the bladder with saline or 0.25% acetic acid. Transcutaneous electrical stimulation (5 Hz) of the cat hind foot at 2 to 4 times the threshold intensity needed to induce observable toe movement was applied to suppress acetic acid induced bladder overactivity. Tramadol (1 to 3 mg/kg intravenously) was administered to enhance foot inhibition.
  
  
  RESULTS
  Acetic acid irritated the bladder, induced bladder overactivity and significantly decreased bladder capacity to a mean ± SE of 26% ± 5% of saline control capacity (p <0.01). Without tramadol, foot stimulation at 2 and 4 threshold intensity applied during acetic acid cystometrograms significantly increased bladder capacity to a mean of 47% ± 5% and 62% ± 6% of saline control capacity, respectively (p <0.05). Without foot stimulation, tramadol (1 mg/kg) only slightly changed bladder capacity to a mean of 39% ± 2% of saline control capacity (p >0.05), while 3 mg/kg significantly increased capacity to 85% ± 14% that of control (p <0.05). However, 1 mg/kg tramadol combined with foot stimulation increased bladder capacity to a mean of 71% ± 18% (2 threshold intensity) and 84% ± 14% (4 threshold intensity), respectively, which did not significantly differ from saline control capacity. In addition, long lasting (greater than 1.5 to 2 hours) post-stimulation inhibition was induced by foot stimulation combined with 3 mg/kg tramadol treatment.
  
  
  CONCLUSIONS
  This study suggests a new treatment strategy for overactive bladder by combining foot stimulation with a low dose of tramadol, which is noninvasive and has potentially high efficacy and fewer adverse effects.
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Abhijith D
authors.initials: AD
authors.lastname: Mally
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Matsuta
authors.forename: Bing
authors.initials: B
authors.lastname: Shen
authors.forename: Jicheng
authors.initials: J
authors.lastname: Wang
authors.forename: James R
authors.initials: JR
authors.lastname: Roppolo
authors.forename: William C
authors.initials: WC
authors.lastname: de Groat
authors.forename: Changfeng
authors.initials: C
authors.lastname: Tai
mesh_terms: D019342:Acetic Acid / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000818:Animals; D002415:Cats; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004558:Electric Stimulation / Q000379:methods*; D005260:Female; D005528:Foot; D007262:Infusions, Intravenous; D008297:Male; D011897:Random Allocation; D012016:Reference Values; D014147:Tramadol / Q000008:administration & dosage*; D016896:Treatment Outcome; D053201:Urinary Bladder, Overactive / Q000139:chemically induced / Q000628:therapy*
chemical_list: D000701:Analgesics, Opioid; D014147:Tramadol; D019342:Acetic Acid