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Inhibitory effects of retigabine, a Kv7 channel activator, on mechanosensitive primary bladder afferent activities and nociceptive behaviors in rats
Author(s) -
Aizawa Naoki,
Wakamatsu Daisuke,
Kida Jun,
Otsuki Takeya,
Saito Yasuho,
Matsuya Hidekazu,
Homma Yukio,
Igawa Yasuhiko
Publication year - 2017
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.22920
Subject(s) - nociception , medicine , resiniferatoxin , mechanosensitive channels , licking , anesthesia , pharmacology , stimulation , trpv1 , ion channel , transient receptor potential channel , receptor
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 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). Results 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. Conclusion 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.