Trigeminal antihyperalgesic effect of intranasal carbon dioxide

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• 作者：Alex ; er Z. Tzabazis ; Sharon H. Niv ; Neil A. Manering ; Mikhail Klyukinov ; Jason M. Cuellar ; Anish Bhatnagar ; David C. Yeomans
• 关键词：Trigeminal ; Pain ; Hyperalgesia ; Hypersensitivity ; Capsaicin ; TRPV₁ ; ASIC ; Carbon dioxide
• 刊名：Life Sciences
• 出版年：2010
• 出版时间：3 July 2010
• 年：2010
• 卷：87
• 期：1-2
• 页码：36-41
• 全文大小：318 K

文摘

class=""h4"">Aims

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.

class=""h4"">Main methods

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 mimic the underlying mechanism.

class=""h4"">Key findings

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 pH 4, but not pH 5, buffer solution to the nasal mucosa. As with CO₂ application, the antihyperalgesic effect of intranasal pH 4 buffer was blocked by nasal application of antagonists to ASICs and TRPV₁ receptors.

class=""h4"">Significance

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.