title: Inhibitory effects of retigabine, a Kv7 channel activator, on mechanosensitive primary bladder afferent activities and nociceptive behaviors in rats.
abstract: Kv7 voltage-gated potassium channels have been suggested to modulate mechano-afferent transduction and nociception in the bladder. We investigated the effects of retigabine, a Kv7 channel activator, on rhythmic bladder contractions (RBCs), and single-unit afferent activities (SAAs) of the primary bladder mechanosensitive afferent nerve fibers in urethane-anesthetized rats. In addition, the effects of pretreatment with retigabine on the nociceptive behaviors provoked by an intravesical instillation of resiniferatoxin (RTX) were evaluated in the conscious condition.
  
  
  
  Female Sprague-Dawley rats were used. Under urethane anesthesia, saline was instilled into the bladder until RBCs were induced reproducibly. Then, the effects of intravenous, cumulative administrations of retigabine (0.1-3 mg/kg) or vehicle (saline) on RBCs were assessed. In separate animals, SAAs of Aδ- and C-fibers were identified by electrical stimulation of the pelvic nerve and by bladder distention with saline. After baseline recording, vehicle or retigabine (0.01-1 mg/kg) was administered intravenously and further recordings were performed. Under pretreatment with vehicle or retigabine (3 mg/kg intraperitoneally), the frequencies of lower abdominal licking and freezing were counted and scored as the bladder nociceptive behaviors induced by intravesical RTX instillation (3 µM, 0.3 ml).
  
  
  
  Retigabine dose-dependently decreased both the frequency and the amplitude of RBCs and SAAs of both Aδ- and C-fibers. The effect on RBCs was more potent on the frequency than the amplitude. Retigabine inhibited the RTX-induced abdominal licking, but not freezing.
  
  
  
  Kv7 channels are likely to be implicated in inhibition of bladder mechano- and nociceptive sensory transduction. Neurourol. Urodynam. 36:280-285, 2017. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Department of Continence Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Aizawa
authors.affiliation: Discovery Research Laboratories 4, Department of Biology & Pharmacology, ONO Pharmaceutical Co., Ltd., Osaka, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Wakamatsu
authors.affiliation: Discovery Research Laboratories 4, Department of Biology & Pharmacology, ONO Pharmaceutical Co., Ltd., Osaka, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kida
authors.affiliation: Discovery Research Laboratories 4, Department of Biology & Pharmacology, ONO Pharmaceutical Co., Ltd., Osaka, Japan.
authors.forename: Takeya
authors.initials: T
authors.lastname: Otsuki
authors.affiliation: Department of Urology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Yasuho
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Discovery Research Laboratories 4, Department of Biology & Pharmacology, ONO Pharmaceutical Co., Ltd., Osaka, Japan.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Matsuya
authors.affiliation: Department of Urology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Homma
authors.affiliation: Department of Continence Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Igawa
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002219:Carbamates / Q000494:pharmacology*; D005260:Female; D040542:Mechanotransduction, Cellular / Q000187:drug effects*; D049990:Membrane Transport Modulators / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000187:drug effects*; D059225:Nociception / Q000187:drug effects*; D010655:Phenylenediamines / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000819:agonists*; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000294:innervation*
chemical_list: D002219:Carbamates; D049990:Membrane Transport Modulators; D010655:Phenylenediamines; D024642:Potassium Channels, Voltage-Gated; C101866:ezogabine
keywords: KCNQ potassium channels; Sprague Dawley rats; afferent; retigabine; urinary bladder