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

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. 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. 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) 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. 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. 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 μ mol 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). 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.British Journal of Pharmacology (2003) 139 , 49–58. doi: 10.1038/sj.bjp.0705234