Capsaicin Indirectly Suppresses Voltage-Gated Na+ Currents Through TRPV1 in Rat Dorsal Root Ganglion Neurons
Capsaicin Indirectly Suppresses Voltage-Gated Na+ Currents Through TRPV1 in Rat Dorsal Root Ganglion Neurons
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DOI：
10.1213/ane.0b013e318204ea5b
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发表时间：
2011-03-01
影响因子：
5.7
通讯作者：
Tsuneyoshi, Isao
中科院分区：
文献类型：
--
作者：
Onizuka, Shin;Yonaha, Tetsu;Tsuneyoshi, Isao
背景：辣椒素用于治疗各种类型的慢性疼痛，包括关节炎和三叉神经痛。尽管辣椒素的细胞效应已被广泛研究，但辣椒素对伤害性传入神经元细胞内钠离子浓度和电压门控性钠电流的影响知之甚少。方法：采用全细胞膜片钳技术和细胞内钠成像技术，研究辣椒素对河豚毒素敏感(TTx-S)和抗性(TTx-r)Ina+的影响。方法：采用全细胞膜片钳技术和细胞内钠成像技术，研究辣椒素对大鼠背根神经节神经元TTx-S和TTx-r组分Ina+的影响。结果：在TTx-S和TTx-r Ina+细胞中，辣椒素(0.1~10mU M)均以剂量依赖的方式减少内向电流。辣椒素可引起稳态失活曲线的超极化位移。强而选择性的瞬时受体电位香草素1(TRPV1)拮抗剂SB366791(10 MU M)可显著减弱INa+的还原。辣椒素可引起心肌细胞[Na+]i升高，SB366791(10 MU M)可显著抑制[Na+]i升高。辣椒素可通过增加[Na+]i来抑制[Na+]i，并引起稳态失活曲线的超极化漂移。结论：辣椒素通过TRPV1使[Na+]i升高，从而降低TTx-S和TTx-r INA+。(Anesth Analg 2011；112：703-9)
BACKGROUND: Capsaicin is used to treat a variety of types of chronic pain, including arthritis and trigeminal neuralgia. Although the cellular effects of capsaicin have been widely studied, little is known about the effects of capsaicin on intracellular sodium ([Na+]i) concentrations and voltage-gated Na+ currents (INa+) in nociceptive afferent neurons. Therefore, in this study we sought to characterize the effect of capsaicin on tetrodotoxin-sensitive (TTX-s) and resistant (TTX-r) INa+.METHODS: The effects of capsaicin on INa+ in rat dorsal root ganglion neurons were studied for both TTX-s and TTX-r components using whole-cell patch-clamp techniques and intracellular sodium imaging.RESULTS: In both TTX-s and TTX-r INa+ of capsaicin-sensitive neurons, capsaicin (0.1 to 10 mu M) reduced inward currents in a dose-dependent manner. Capsaicin induced a hyperpolarization shift in the steady-state inactivation curves. SB366791 (10 mu M), a potent and selective transient receptor potential vanilloid member1 (TRPV1) antagonist, significantly attenuated the reduction in INa+. Capsaicin induced an increase in the [Na+]i, and SB366791 (10 mu M) significantly reduced the [Na+]i increase. An increase in [Na+]i with gramicidin also dependently suppressed INa+ and induced a hyperpolarization shift in the steady-state inactivation curves by increasing the [Na+]i.CONCLUSION: The findings suggest that capsaicin decreases both TTX-s and TTX-r INa+ as a result of an increase in [Na+]i through TRPV1. (Anesth Analg 2011;112:703-9)