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

1. An increasing-temperature hot plate (ITHP) was introduced to measure the noxious heat threshold (45.3+/-0.3 degrees 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 200 mg 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 degrees C drop) 5 min 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 degrees 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 alpha,beta-methylene-ATP (0.3 micromol 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 degrees 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.