Effect of transient receptor potential vanilloid 1 (TRPV1) receptor antagonist compounds SB705498, BCTC and AMG9810 in rat models of thermal hyperalgesia measured with an increasing-temperature water bath.

Abstract

The transient receptor potential vanilloid 1 (TRPV1) receptor is activated by noxious heat, various endogenous mediators and exogenous irritants. The aim of the present study was to compare three TRPV1 receptor antagonists (SB705498, BCTC and AMG9810) in rat models of heat hyperalgesia. The behavioural noxious heat threshold, defined as the lowest temperature evoking nocifensive reaction, was measured with an increasing-temperature water bath. The effects of TRPV1 receptor antagonists were assessed in thermal hyperalgesia induced by the TRPV1 agonist resiniferatoxin (RTX), mild heat injury (51 degrees C, 20s) or plantar incision in rats. The control heat threshold was 43.2+/-0.4 degrees C. RTX induced an 8-10 degrees C decrease in heat threshold which was dose-dependently inhibited by oral pre-treatment with any of the TRPV1 receptor antagonists with a minimum effective dose of 1mg/kg. The mild heat injury-evoked 7-8 degrees C heat threshold drop was significantly reversed by all three antagonists injected i.p. as post-treatment. The minimum effective doses were as follows: SB705498 10, BCTC 3 and AMG9810 1mg/kg. Plantar incision-induced heat threshold drop (7-8 degrees C) was dose-dependently diminished by an oral post-treatment with any of the antagonists with minimum effective doses of 10, 3 and 3mg/kg, respectively. Assessment of RTX hyperalgesia by measurement of the paw withdrawal latency with a plantar test apparatus yielded 30 mg/kg minimum effective dose for each antagonist. In conclusion, measurement of the noxious heat threshold with the increasing-temperature water bath is suitable to sensitively detect the effects of TRPV1 receptor antagonists in thermal hyperalgesia models.

• Authors: Valéria Tékus, Kata Bölcskei, Agnes Kis-Varga, László Dézsi, Eva Szentirmay, András Visegrády, Csilla Horváth, János Szolcsányi, Gábor Petho
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 641 Issue 2-3 Pg. 135-41 (Sep 01 2010) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 20534382 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2010 Elsevier B.V. All rights reserved.

Chemical References

• 3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo(b)(1,4)dioxin-6-yl)acrylamide
• Acrylamides
• Bridged Bicyclo Compounds, Heterocyclic
• Diterpenes
• N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carboxamide
• Pyrazines
• Pyridines
• Pyrrolidines
• SB 705498
• TRPV Cation Channels
• TRPV1 receptor
• Urea
• resiniferatoxin

Topics

• Acrylamides (antagonists & inhibitors)
• Animals
• Bridged Bicyclo Compounds, Heterocyclic (antagonists & inhibitors)
• Cold Temperature
• Disease Models, Animal
• Diterpenes (pharmacology)
• Dose-Response Relationship, Drug
• Female
• Hot Temperature (adverse effects)
• Hyperalgesia (chemically induced, drug therapy)
• Pain (drug therapy)
• Pyrazines (antagonists & inhibitors)
• Pyridines (antagonists & inhibitors)
• Pyrrolidines (antagonists & inhibitors)
• Rats
• Rats, Sprague-Dawley
• TRPV Cation Channels (antagonists & inhibitors)
• Urea (analogs & derivatives, antagonists & inhibitors)