PMID- 26536146
OWN - NLM
STAT- MEDLINE
DCOM- 20171207
LR  - 20181202
IS  - 1520-6777 (Electronic)
IS  - 0733-2467 (Linking)
VI  - 36
IP  - 2
DP  - 2017 Feb
TI  - Inhibitory effects of retigabine, a Kv7 channel activator, on mechanosensitive 
      primary bladder afferent activities and nociceptive behaviors in rats.
PG  - 280-285
LID - 10.1002/nau.22920 [doi]
AB  - AIMS: 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. METHODS: 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 Adelta- 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 microM, 0.3 ml). RESULTS: 
      Retigabine dose-dependently decreased both the frequency and the amplitude of 
      RBCs and SAAs of both Adelta- 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. CONCLUSION: Kv7 channels are likely to be implicated 
      in inhibition of bladder mechano- and nociceptive sensory transduction. 
      Neurourol. Urodynam. 36:280-285, 2017. (c) 2015 Wiley Periodicals, Inc.
CI  - (c) 2015 Wiley Periodicals, Inc.
FAU - Aizawa, Naoki
AU  - Aizawa N
AD  - Department of Continence Medicine, The University of Tokyo Graduate School of 
      Medicine, Tokyo, Japan.
FAU - Wakamatsu, Daisuke
AU  - Wakamatsu D
AD  - Discovery Research Laboratories 4, Department of Biology & Pharmacology, ONO 
      Pharmaceutical Co., Ltd., Osaka, Japan.
FAU - Kida, Jun
AU  - Kida J
AD  - Discovery Research Laboratories 4, Department of Biology & Pharmacology, ONO 
      Pharmaceutical Co., Ltd., Osaka, Japan.
FAU - Otsuki, Takeya
AU  - Otsuki T
AD  - Discovery Research Laboratories 4, Department of Biology & Pharmacology, ONO 
      Pharmaceutical Co., Ltd., Osaka, Japan.
FAU - Saito, Yasuho
AU  - Saito Y
AD  - Department of Urology, The University of Tokyo Graduate School of Medicine, 
      Tokyo, Japan.
FAU - Matsuya, Hidekazu
AU  - Matsuya H
AD  - Discovery Research Laboratories 4, Department of Biology & Pharmacology, ONO 
      Pharmaceutical Co., Ltd., Osaka, Japan.
FAU - Homma, Yukio
AU  - Homma Y
AD  - Department of Urology, The University of Tokyo Graduate School of Medicine, 
      Tokyo, Japan.
FAU - Igawa, Yasuhiko
AU  - Igawa Y
AD  - Department of Continence Medicine, The University of Tokyo Graduate School of 
      Medicine, Tokyo, Japan.
LA  - eng
PT  - Journal Article
DEP - 20151104
PL  - United States
TA  - Neurourol Urodyn
JT  - Neurourology and urodynamics
JID - 8303326
RN  - 0 (Carbamates)
RN  - 0 (Membrane Transport Modulators)
RN  - 0 (Phenylenediamines)
RN  - 0 (Potassium Channels, Voltage-Gated)
RN  - 12G01I6BBU (ezogabine)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/*drug effects
MH  - Carbamates/*pharmacology
MH  - Female
MH  - Mechanotransduction, Cellular/*drug effects
MH  - Membrane Transport Modulators/*pharmacology
MH  - Neurons, Afferent/*drug effects
MH  - Nociception/*drug effects
MH  - Phenylenediamines/*pharmacology
MH  - Potassium Channels, Voltage-Gated/*agonists
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Urinary Bladder/*innervation
OTO - NOTNLM
OT  - KCNQ potassium channels
OT  - Sprague Dawley rats
OT  - afferent
OT  - retigabine
OT  - urinary bladder
EDAT- 2015/11/05 06:00
MHDA- 2017/12/08 06:00
CRDT- 2015/11/05 06:00
PHST- 2015/08/04 00:00 [received]
PHST- 2015/10/13 00:00 [accepted]
PHST- 2015/11/05 06:00 [pubmed]
PHST- 2017/12/08 06:00 [medline]
PHST- 2015/11/05 06:00 [entrez]
AID - 10.1002/nau.22920 [doi]
PST - ppublish
SO  - Neurourol Urodyn. 2017 Feb;36(2):280-285. doi: 10.1002/nau.22920. Epub 2015 Nov 
      4.