title: Kv7.2-7.5 voltage-gated potassium channel (KCNQ2-5) opener, retigabine, reduces capsaicin-induced visceral pain in mice.
abstract: K(v)7.2-7.5 voltage-gated potassium channels (KCNQ2-5) are associated with M-current and known to distribute in the nociceptive sensory pathway (e.g., dorsal root ganglia and spinal cord). Opening of these channels leads to cell membrane hyperpolarization that results in decreased neuronal action potentials. Since, KCNQ/M-current is located in the visceral sensory system, we examined the anti-nociceptive effect of the KCNQ opener, retigabine, on visceral pain induced by an intracolonic injection of capsaicin in mice. Intraperitoneal administration of retigabine (1, 3 and 10 mg/kg) dose-dependently suppressed visceral pain behavior (i.e., the number of licking) induced by the capsaicin treatment and prolonged the latency to first licking. These data provide the first evidence that increased KCNQ channel conductance plays an inhibitory role in the visceral pain pathway.
authors.affiliation: Pharmacology Department, Tsukuba Research Laboratories, High Throughput Biology, Discovery Research, GlaxoSmithKline, 43 Wadai, Tsukuba 300-4247, Japan.
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Hirano
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kuratani
authors.forename: Masato
authors.initials: M
authors.lastname: Fujiyoshi
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Tashiro
authors.forename: Etsuko
authors.initials: E
authors.lastname: Hayashi
authors.forename: Mine
authors.initials: M
authors.lastname: Kinoshita
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use; D002211:Capsaicin / Q000037:antagonists & inhibitors; D002219:Carbamates / Q000494:pharmacology* / Q000627:therapeutic use; D003106:Colon / Q000187:drug effects / Q000294:innervation; D051658:KCNQ2 Potassium Channel / Q000819:agonists* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009619:Nociceptors / Q000187:drug effects* / Q000378:metabolism; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010655:Phenylenediamines / Q000494:pharmacology* / Q000627:therapeutic use; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism; D017833:Visceral Afferents / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D002219:Carbamates; D051658:KCNQ2 Potassium Channel; D010655:Phenylenediamines; C101866:ezogabine; D002211:Capsaicin