title: Tannic acid modulates excitability of sensory neurons and nociceptive behavior and the Ionic mechanism.
abstract: M/Kv7 K(+) channels, Ca(2+)-activated Cl(-) channels (CaCCs) and voltage gated Na(+) channels expressed in dorsal root ganglia (DRG) play an important role in nociception. Tannic acid has been proposed to be involved in multiple beneficial health effects; tannic acid has also been described to be analgesic. However the underlying mechanism is unknown. In this study, we investigated the effects of tannic acid on M/Kv7 K(+), Na(+) currents and CaCCs, and the effects on bradykinin-induced nociceptive behavior. A perforated patch technique was used. The bradykinin-induced rat pain model was used to assess the analgesic effect of tannic acid. We demonstrated that tannic acid enhanced M/Kv7 K(+) currents but inhibited bradykinin-induced activation of CaCC/TMEM16A currents in rat small DRG neurons. Tannic acid potentiated Kv7.2/7.3 and Kv7.2 currents expressed in HEK293B cells, with an EC50 of 7.38 and 5.40 µM, respectively. Tannic acid inhibited TTX-sensitive and TTX-insensitive currents of small DRG neurons with IC50 of 5.25 and 8.43 µM, respectively. Tannic acid also potently suppressed the excitability of small DRG neurons. Furthermore, tannic acid greatly reduced bradykinin-induced pain behavior of rats. This study thus demonstrates that tannic acid is an activator of M/Kv7 K(+) and an inhibitor of voltage-gated Na(+) channels and CaCC/TMEM16A, which may underlie its inhibitory effects on excitability of DRG neurons and its analgesic effect. Tannic acid could be a useful agent in treatment of inflammatory pain conditions such as osteoarthritis, rheumatic arthritis and burn pain.
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang, China; Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Huiran
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang, China.
authors.forename: Najing
authors.initials: N
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang, China; Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang, China.
authors.forename: Jiaxi
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang, China.
authors.forename: Man
authors.initials: M
authors.lastname: Si
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang, China.
authors.forename: Zhanfeng
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang, China.
authors.forename: Xiaona
authors.initials: X
authors.lastname: Du
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang, China. Electronic address: zhanghl@hebmu.edu.cn.
authors.forename: Hailin
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000075369:Anoctamin-1; D001522:Behavior, Animal / Q000187:drug effects; D001920:Bradykinin; D018118:Chloride Channels / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D057809:HEK293 Cells; D006801:Humans; D051656:KCNQ Potassium Channels / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D051658:KCNQ2 Potassium Channel / Q000819:agonists / Q000378:metabolism; D051659:KCNQ3 Potassium Channel / Q000819:agonists / Q000378:metabolism; D008564:Membrane Potentials; D059225:Nociception / Q000187:drug effects*; D059226:Nociceptive Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000378:metabolism; D013634:Tannins / Q000494:pharmacology*; D014162:Transfection; D061567:Voltage-Gated Sodium Channel Blockers / Q000494:pharmacology*; D061566:Voltage-Gated Sodium Channels / Q000187:drug effects* / Q000378:metabolism
chemical_list: C552942:ANO1 protein, rat; D000700:Analgesics; D000075369:Anoctamin-1; D018118:Chloride Channels; D051656:KCNQ Potassium Channels; D051658:KCNQ2 Potassium Channel; C496914:KCNQ2 protein, human; D051659:KCNQ3 Potassium Channel; C496916:KCNQ3 protein, human; D013634:Tannins; D061567:Voltage-Gated Sodium Channel Blockers; D061566:Voltage-Gated Sodium Channels; D001920:Bradykinin
keywords: Bradykinin; CaCCs; M/Kv7 K(+) currents; Pain; Tannic acid; Voltage-gated Na(+) currents