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

• Published in: European journal of pharmacology 2010-09, Vol.641 (2), p.135-141
• Main Authors: TEKUS, Valéria, BÖLCSKEI, Kata, KIS-VARGA, Agnes, DEZSI, László, SZENTIRMAY, Eva, VISEGRADY, András, HORVATH, Csilla, SZOLCSANYI, János, PETHÖ, Gábor
• Format: Article
• Language: English
• Subjects: Acrylamides - antagonists & inhibitors; Animals; Baths; Biological and medical sciences; Bridged Bicyclo Compounds, Heterocyclic - antagonists & inhibitors; Capsaicin receptors; Cold Temperature; Disease Models, Animal; Diterpenes - pharmacology; Dose-Response Relationship, Drug; Female; Heat; Heat injury; Hot Temperature - adverse effects; Hyperalgesia - chemically induced; Hyperalgesia - drug therapy; Increasing-temperature water bath; Injuries; Medical sciences; Pain - drug therapy; Pain perception; Pharmacology. Drug treatments; Plantar incision; Pyrazines - antagonists & inhibitors; Pyridines - antagonists & inhibitors; Pyrrolidines - antagonists & inhibitors; Rats; Rats, Sprague-Dawley; Resiniferatoxin; Thermonociception; transient receptor potential proteins; Transient receptor potential vanilloid type 1 receptor antagonist; TRPV Cation Channels - antagonists & inhibitors; Urea - analogs & derivatives; Urea - antagonists & inhibitors; Water temperature
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2010.05.052

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 °C, 20 s) or plantar incision in rats. The control heat threshold was 43.2 ± 0.4 °C. RTX induced an 8–10 °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 1 mg/kg. The mild heat injury-evoked 7–8 °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 1 mg/kg. Plantar incision-induced heat threshold drop (7–8 °C) was dose-dependently diminished by an oral post-treatment with any of the antagonists with minimum effective doses of 10, 3 and 3 mg/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.