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[Abstract Title]. - Society for Neuroscience

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have agonist properties at selective TRP channels. Some of these chemicals produce a<br />

neurogenic inflammatory response, which is produced by a locally-, as well as a centrallymediated<br />

release of vasoactive peptides and thought to be important in some types of<br />

inflammatory pain. For example, the TRPV1 agonist, capsaicin, produces an intense „burning‟<br />

pain sensation followed by radiating areas of hyperalgesia and allodynia following intradermal or<br />

topical administration. This inflammatory response is visible as a “flare” surrounding the site of<br />

injection. Quantification of flare can be accomplished by using laser Doppler imaging, which<br />

measures superficial blood flow in the skin.<br />

In the present study, laser Doppler imaging was used to evaluate the flare response to TRP<br />

agonists. The TRPV1, TRPA1, and TRPM8 agonists capsaicin (0.1 - 3 mg), mustard oil (0.3%-<br />

10%), and menthol (50%), respectively, were topically administered in anesthetized rats.<br />

Capsaicin dose-dependently produced flare, with the maximal flare response occurring 45 min<br />

(191% increase from baseline) after application of 1 mg. When administered 120 min be<strong>for</strong>e<br />

capsaicin, the selective TRPV1 antagonist, JNJ-17203212 (30 mg/kg; p.o), blocked the flare<br />

response induced by topical administration of 0.3 mg capsaicin. Mustard oil, produced the<br />

greatest flare response at 30 min (120% increase from baseline) at a concentration of 0.3%.<br />

Higher concentrations of mustard oil produced less flare at the site of application, though flare<br />

outside the area of application was substantially greater. The flare response to menthol was not<br />

substantially different than that of vehicle. These results suggest that laser Doppler imaging can<br />

be useful <strong>for</strong> evaluating compounds <strong>for</strong> their ability to modify the flare response produced by<br />

TRP agonists.<br />

Disclosures: V.A. Kenigs, Johnson & Johnson PR&D, A. Employment (full or part-time); M.R.<br />

Brandt, Johnson & Johnson PRD, A. Employment (full or part-time); C.M. Flores, Johnson &<br />

Johnson PR&D, A. Employment (full or part-time).<br />

Poster<br />

265. Nociceptors II<br />

Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm<br />

Program#/Poster#: 265.21/EE22<br />

Topic: B.02.t. TRP Channels<br />

<strong>Title</strong>: Development of a high-content automated electrophysiological assay combining TRPV1<br />

pH and voltage-dependent activations<br />

Authors: O. RADRESA, *S. ZICHA, M. VALIQUETTE, J. DUCHARME;<br />

AstraZeneca R&D Montreal, St-Laurent, QC, Canada

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