Antihyperalgesic effect of TRPV1 receptor antagonists SB705498, BCTC, AMG9810 in the rat measured with an increasing-temperature water bath
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1
University of Pécs and Gedeon Richter Ltd, Analgesic Research Laboratory, Hungary
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2
Pharmacology and Drug Safety Research, Gedeon Richter Plc., Laboratory of Neuropharmacology, Hungary
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3
University of Pecs, Department of Pharmacology and Pharmacotherapy, Hungary
The TRPV1 receptor is a non-selective cation channel expressed in the membranes of polymodal nociceptors activated by various noxious stimuli such as noxious heat, acid (low pH), and various endogenous mediators and exogenous irritants. The aim of the present study was to characterise TRPV1 antagonists (SB705498, BCTC, AMG9810) in rat models of thermal hyperalgesia.
The noxious heat threshold of rats, defined as the lowest temperature evoking nocifensive reaction, was measured with a novel increasing-temperature water bath. Thermal hyperalgesia was induced by 1; intraplantar injection of the TRPV1 receptor agonist resiniferatoxin (RTX, 0.01µg) 2; mild heat injury (51°C, 20 s), 3; surgical incision of the paw.
The control noxious heat threshold of rats was 43.2±0.4°C. After RTX injection a marked, 8-10°C drop of heat threshold was measured. Pretreatment with any of the three TRPV1 receptor antagonists dose-dependently inhibited the RTX-induced heat hyperalgesia with minimum effective doses (MED) of 1 mg/kg p.o. for each compound. In contrast, measurement of paw withdrawal latency with a plantar test apparatus to assess RTX hyperalgesia yielded much higher MEDs. Heat injury induced a 7-8°C noxious heat threshold drop which was reversed by posttreatment with any of the three compounds (MED: SB705498 10 mg/kg i.p., BCTC 3 mg/kg i.p., AMG9810 1 mg/kg i.p.) Surgical incision decreased the noxious heat threshold by 7-8 °C. All three antagonists applied as a posttreatment dose-dependently diminished the postoperative noxious heat threshold drop (MED: SB705498 10 mg/kg i.p., BCTC 3 mg/kg i.p., AMG9810 3 mg/kg i.p.).
Measurement of the noxious heat threshold with the increasing-temperature water bath was remarkably sensitive to detect the effect of TRPV1 antagonists in the RTX-induced thermal hyperalgesia model. These compounds also attenuated heat injury or incision-induced thermal hyperalgesia, which confirms the role of TRPV1 receptor in these conditions.
Conference:
IBRO International Workshop 2010, Pécs, Hungary, 21 Jan - 23 Jan, 2010.
Presentation Type:
Poster Presentation
Topic:
Sensory and motor systems
Citation:
Tékus
V,
Bölcskei
K,
Kis-Varga
Á,
Dézsi
L,
Horváth
C,
Szolcsányi
J and
Petho
G
(2010). Antihyperalgesic effect of TRPV1 receptor antagonists SB705498, BCTC, AMG9810 in the rat measured with an increasing-temperature water bath.
Front. Neurosci.
Conference Abstract:
IBRO International Workshop 2010.
doi: 10.3389/conf.fnins.2010.10.00154
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Received:
29 Apr 2010;
Published Online:
29 Apr 2010.
*
Correspondence:
Kata Bölcskei, University of Pécs and Gedeon Richter Ltd, Analgesic Research Laboratory, Pecs, Hungary, kata.bolcskei@aok.pte.hu