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.
Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Neuropharmacology Research Group of the Hungarian Academy of Sciences, University of Pécs, Szigeti u. 12, H-7624 Pécs, Hungary.
Róbert
R
Almási
Gábor
G
Pethö
Kata
K
Bölcskei
János
J
Szolcsányi
D000082:Acetaminophen / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004008:Diclofenac / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006614:Hindlimb; D006358:Hot Temperature; D051379:Mice; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects; D010146:Pain / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods; D010812:Physical Stimulation; D051381:Rats; D017208:Rats, Wistar; D011955:Receptors, Drug / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics; D015203:Reproducibility of Results; D012684:Sensory Thresholds / Q000187:drug effects*; D013697:Thermosensing / Q000187:drug effects*; D013997:Time Factors
D000700:Analgesics; D004224:Diterpenes; D011955:Receptors, Drug; D004008:Diclofenac; D000082:Acetaminophen; D009020:Morphine; C024353:resiniferatoxin