Trigeminal antihyperalgesic effect of intranasal carbon dioxide

• Published in: Life sciences (1973) 2010-07, Vol.87 (1), p.36-41
• Main Authors: Tzabazis, Alexander Z., Niv, Sharon H., Manering, Neil A., Klyukinov, Mikhail, Cuellar, Jason M., Bhatnagar, Anish, Yeomans, David C.
• Format: Article
• Language: English
• Subjects: Acid Sensing Ion Channels; Administration, Intranasal; Animals; ASIC; Behavior, Animal - drug effects; Capsaicin; Carbon dioxide; Carbon Dioxide - administration & dosage; Carbon Dioxide - pharmacology; Disease Models, Animal; Dose-Response Relationship, Drug; Hydrogen-Ion Concentration; Hyperalgesia; Hyperalgesia - drug therapy; Hypersensitivity; Male; Nasal Mucosa - metabolism; Nerve Tissue Proteins - drug effects; Nerve Tissue Proteins - metabolism; Pain; Pain Measurement; Rats; Rats, Sprague-Dawley; Sodium Channels - drug effects; Sodium Channels - metabolism; Trigeminal; Trigeminal Nerve; TRPV 1; TRPV Cation Channels - drug effects; TRPV Cation Channels - metabolism
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2010.05.013

Clinical studies demonstrate attenuation of trigeminal-related pain states such as migraine by intranasal CO 2 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 mimic the underlying mechanism. Intranasal CO 2 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 CO 2 application. Pharmacologic blockade of ASICs or TRPV 1 receptor significantly attenuated the antihyperalgesic effect of CO 2 application. The effect of intranasal CO 2 application could be mimicked by application of pH 4, but not pH 5, buffer solution to the nasal mucosa. As with CO 2 application, the antihyperalgesic effect of intranasal pH 4 buffer was blocked by nasal application of antagonists to ASICs and TRPV 1 receptors. Our results indicate that intranasal CO 2 application results in a subsequent attenuation of trigeminal nociception, mediated by protonic activation of TRPV 1 and ASIC channels. A potential central mechanism for this attenuation is discussed. The antihyperalgesic effects of intranasal CO 2 application might be useful for the treatment of trigeminal pain states.