Tannic acid modulates excitability of sensory neurons and nociceptive behavior and the Ionic mechanism.
Tannic acid modulates excitability of sensory neurons and nociceptive behavior and the Ionic mechanism.
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DOI：
10.1016/j.ejphar.2015.06.048
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发表时间：
2015-10
影响因子：
5
通讯作者：
Xuan Zhang;Huiran Zhang;N. Zhou;Jiaxi Xu;M. Si;Zhanfeng Jia;Xiaona Du;Hailin Zhang
中科院分区：
文献类型：
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作者：
Xuan Zhang;Huiran Zhang;N. Zhou;Jiaxi Xu;M. Si;Zhanfeng Jia;Xiaona Du;Hailin Zhang
背根神经节（DRG）表达的M/Kv 7钾通道、钙激活的氯通道（CaCCs）和电压门控的钠通道在伤害性感受中起重要作用。单宁酸被认为具有多种有益健康的作用;单宁酸也被描述为镇痛剂。然而，其潜在机制尚不清楚。本实验研究了单宁酸对M/Kv 7细胞K+、Na+电流和CaCCs的影响，以及对缓激肽诱导的伤害性行为的影响。使用穿孔补片技术。采用缓激肽致痛大鼠模型观察鞣酸的镇痛作用。我们证明，鞣酸增强M/Kv 7 K+电流，但抑制缓激肽诱导的激活大鼠小DRG神经元的CaCC/TMEM 16 A电流。单宁酸增强HEK 293 B细胞中表达的Kv7.2/7.3和Kv7.2电流，EC 50分别为7.38和5.40 µM。单宁酸抑制小DRG神经元的TTX敏感和TTX不敏感电流，IC 50分别为5.25和8.43 µM。单宁酸还有效地抑制小DRG神经元的兴奋性。此外，鞣酸大大减少缓激肽诱导的大鼠疼痛行为。因此，本研究表明，单宁酸是M/Kv 7 K+的激活剂，也是电压门控Na+通道和CaCC/TMEM 16 A的抑制剂，这可能是其对背根神经节神经元兴奋性的抑制作用及其镇痛作用的基础。鞣酸可用于治疗炎性疼痛，如骨关节炎、风湿性关节炎和烧伤疼痛。
M/Kv7 K+channels, Ca2+-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 EC50of 7.38 and 5.40 µM, respectively. Tannic acid inhibited TTX-sensitive and TTX-insensitive currents of small DRG neurons with IC50of 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.