title: Combination of foot stimulation and tolterodine treatment eliminates bladder overactivity in cats.
abstract: OBJECTIVE
  To determine whether transcutaneous foot stimulation combined with a lower dose tolterodine would inhibit bladder overactivity more effectively than either treatment alone.
  
  
  METHODS
  Cystometrograms were performed on α-chloralose anesthetized cats (N = 6) by infusing 0.25% acetic acid (AA) to induce bladder overactivity. Foot stimulation (5 Hz) was applied at 2 and 4 times the threshold (T) intensity in volts (i.e., 2T or 4T) for inducing toe movement to inhibit bladder overactivity. Cumulative doses of tolterodine (0.003-0.3 mg/kg, i.v.) were also administered to determine the effect of combination treatment.
  
  
  RESULTS
  AA irritation of the bladder significantly (P < 0.0001) reduced bladder capacity to 23.6 ± 7.1% of saline control capacity. Foot stimulation alone at 2T and 4T inhibited bladder overactivity and significantly (P < 0.0001) increased bladder capacity to 50.7 ± 6.8% and 79.0 ± 11.6% of saline control, respectively. Tolterodine alone at 0.3 mg/kg significantly (P < 0.05) increased bladder capacity to 65.6 ± 15.5% of saline control. However, when tolterodine at a threshold dose (0.3 mg/kg) was combined with foot stimulation, the bladder capacity was significantly (P < 0.05) increased to 86.2 ± 6.2% and 107.9 ± 10.6% by 2T and 4T stimulation, respectively. Complete inhibition of bladder overactivity could be achieved at a lower tolterodine dose (0.1 mg/kg) when combined with 4T stimulation (97.0 ± 11.2% of saline control). The amplitude of micturition contraction was not changed by tolterodine treatment.
  
  
  CONCLUSIONS
  This study suggests a novel, efficacious, non-invasive therapy by combining foot stimulation with a lower dose tolterodine to treat bladder overactivity. It also provides the first objective evidence supporting an additive therapeutic benefit of neuromodulation and antimuscarinic combination treatment.
authors.affiliation: Department of Urology, University of Pittsburgh, PA.
authors.forename: Zeyad
authors.initials: Z
authors.lastname: Schwen
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: D000818:Animals; D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D002415:Cats; D003131:Combined Modality Therapy; D003408:Cresols / Q000627:therapeutic use*; D005260:Female; D005528:Foot; D008297:Male; D018727:Muscarinic Antagonists / Q000627:therapeutic use*; D010665:Phenylpropanolamine / Q000627:therapeutic use*; D000068737:Tolterodine Tartrate; D004561:Transcutaneous Electric Nerve Stimulation; D053201:Urinary Bladder, Overactive / Q000628:therapy*
chemical_list: D001559:Benzhydryl Compounds; D003408:Cresols; D018727:Muscarinic Antagonists; D010665:Phenylpropanolamine; D000068737:Tolterodine Tartrate
keywords: antimuscarinics; cat; neuromodulation; overactive bladder; tolterodine
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