Trigeminal antihyperalgesic effect of intranasal carbon dioxide.
Trigeminal antihyperalgesic effect of intranasal carbon dioxide.
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DOI：
10.1016/j.lfs.2010.05.013
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发表时间：
2010-07-03
期刊：
影响因子：
6.1
通讯作者：
Yeomans, David C.
中科院分区：
文献类型：
--
作者：
Tzabazis, Alexander Z.;Niv, Sharon H.;Manering, Neil A.;Klyukinov, Mikhail;Cuellar, Jason M.;Bhatnagar, Anish;Yeomans, David C.
临床研究表明，鼻腔应用二氧化碳可以缓解三叉神经相关的疼痛状态，如偏头痛。这项研究调查了这种观察的潜在机制以及它在逆转三叉神经疼痛和过敏方面的潜在用途。我们采用辣椒素诱导的大鼠三叉神经热痛敏行为模型，鼻腔注射CO2，并用碳酸氢酶、酸敏离子通道(ASICs)、TRPV1阻滞剂以及酸性缓冲溶液等药物来研究和模拟其潜在的机制。鼻腔应用二氧化碳在大鼠身上产生了强烈的剂量依赖的止痛作用，持续了至少一个小时。用多唑胺溶液(Trusopt®眼用溶液)阻断鼻腔碳酸酐酶，仅显示鼻腔应用二氧化碳的止痛作用没有明显降低。药物阻断ASICs或TRPV1受体可显著减弱CO2的止痛作用。鼻腔内应用CO2的效果可以通过向鼻黏膜施加pH 4的缓冲液来模拟，但不能通过向鼻黏膜施加pH 5来模拟。与CO2应用一样，鼻腔应用拮抗剂对ASICs和TRPV1受体的拮抗剂可阻断鼻内pH 4缓冲液的止痛作用。我们的结果表明，鼻腔应用二氧化碳可导致三叉神经伤害性感觉的随后减弱，这是由TRPV1和ASIC通道的质子激活所介导的。讨论了这种衰减的一种潜在的中心机制。鼻腔应用CO2的止痛作用可能有助于三叉神经痛状态的治疗。
Clinical studies demonstrate attenuation of trigeminal-related pain states such as migraine by intranasal CO2 application. This study investigated the underlying mechanisms of this observation and its potential use to reverse trigeminal pain and hypersensitivity. We used a behavioral rat model of capsaicin-induced trigeminal thermal hyperalgesia, intranasal CO2 application and several pharmacologic agents such as carbonic anhydrase, acid-sensing ion channels (ASICs), and TRPV1 blocker as well as acidic buffer solutions to investigate and mimick the underlying mechanism. Intranasal CO2 application produced a robust dose-dependent antihyperalgesic effect in rats that lasted at least one hour. Blockade of nasal carbonic anhydrase with a dorzolamide solution (Trusopt® ophthalmic solution) showed only a non-significant decrease of the antihyperalgesic effect of intranasal CO2 application. Pharmacologic blockade of ASICs or TRPV1 receptor significantly attenuated the antihyperalgesic effect of CO2 application. The effect of intranasal CO2 application could be mimicked by application of pH4, but not pH 5, buffer solution to the nasal mucosa. As with CO2 application, the antihyperalgesic effect of intranasal pH4 buffer was blocked by nasal application of antagonists to ASICs and TRPV1 receptors. Our results indicate that intranasal CO2 application results in a subsequent attenuation of trigeminal nociception, mediated by protonic activation of TRPV1 and ASIC channels. A potential central mechanism for this attenuation is discussed. The antihyperalgesic effects of intranasal CO2 application might be useful for the treatment of trigeminal pain states.
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影响因子：
3
作者：
Hummel, T;Mohammadian, P;Lötsch, J
通讯作者：
Lötsch, J
DOI：
10.1124/jpet.102.040394
发表时间：
2002-12-01
影响因子：
3.5
作者：
Seabrook, GR;Sutton, KG;Jones, AB
通讯作者：
Jones, AB
影响因子：
7.4
作者：
Yeomans, DC;Pirec, V;Proudfit, HK
通讯作者：
Proudfit, HK
影响因子：
2.9
作者：
Tanimoto, T;Takeda, M;Matsumoto, S
通讯作者：
Matsumoto, S
影响因子：
7.4
作者：
Yeomans, DC;Proudfit, HK
通讯作者：
Proudfit, HK