Effect of resiniferatoxin on the noxious heat threshold temperature in the rat: A novel heat allodynia model sensitive to analgesics

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Abstract

1. An increasing-temperature hot plate (ITHP) was introduced to measure the noxious heat threshold (45.3±0.3°C) of unrestrained rats which was reproducible upon repeated determinations at intervals of 5 or 30 min or 1 day. 2. Morphine, diclofenac and paracetamol caused an elevation of the noxious heat threshold following i.p. pretreatment, the minimum effective doses being 3, 10 and 200mg kg -1 respectively. 3. Unilateral intraplantar injection of the VR1 receptor agonist resiniferatoxin (RTX, 0.048 nmol) induced a profound drop of heat threshold to the innocuous range with a maximal effect (8-10°C drop) 5min after RTX administration. This heat allodynia was inhibited by pretreatment with morphine, diclofenac and paracetamol, the minimum effective doses being 1, 1 and 100 mg kg -1 i.p., respectively. 4. The long-term sensory desensitizing effect of RTX was examined by bilateral intraplantar injection (0.048 nmol per paw) which produced, after an initial threshold drop, an elevation (up to 2.9±0.5°C) of heat threshold lasting for 5 days. 5. The VR1 receptor antagonist iodo-resiniferatoxin (I-RTX, 0.05 nmol intraplantarly) inhibited by 51% the heat threshold-lowering effect of intraplantar RTX but not α,β-methylene-ATP (0.3 μmol per paw). I-RTX (0.1 or 1 nmol per paw) failed to alter the heat threshold either acutely (5-60 min) or on the long-term (5 days). The heat threshold of VR1 receptor knockout mice was not different from that of wild-type animals (45.6±0.5 vs 45.2±0.4°C). 6. In conclusion, the RTX-induced drop of heat threshold measured by the ITHP is a novel heat allodynia model exhibiting a high sensitivity to analgesics.

Original languageEnglish
Pages (from-to)49-58
Number of pages10
JournalBritish journal of pharmacology
Volume139
Issue number1
DOIs
Publication statusPublished - May 2003

Keywords

  • Diclofenac
  • Heat allodynia
  • Increasing-temperature hot plate
  • Iodo-resiniferatoxin
  • Morphine
  • Noxious heat threshold temperature
  • Paracetamol
  • Resiniferatoxin
  • Sensory desensitization
  • α,β-methylene-ATP

ASJC Scopus subject areas

  • Pharmacology

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