Heat injury-induced drop of the noxious heat threshold measured with an increasing-temperature water bath: A novel rat thermal hyperalgesia model

Abstract

Conventional thermonociceptive tests are based on measurement of the latency of nocifensive reactions evoked by constant, suprathreshold heat stimuli. In the present study, a novel, increasing-temperature water bath was developed for determination of the noxious heat threshold temperature of lightly restrained conscious rats. One of the hindpaws of a rat was immersed into the water bath whose temperature was increased from 30 °C at a rate of 24 °C/min until the animal withdrew its hindpaw from the water. The corresponding bath temperature was considered as behavioural noxious heat threshold. The heat threshold of untreated rats was 43.5±0.4 °C (n=10) and was reproducible upon repeated measurements at intervals of 10 min for 60 min. Thermal hyperalgesia was induced by mild heat injury (51 °C water for 20 s) which led to a 7–8 °C decrease of the noxious heat threshold. Thermal hyperalgesia was detected at least for 60 min after heat injury. Morphine, diclofenac, ibuprofen and paracetamol administered intraperitoneally 20 min after heat injury dose-dependently inhibited the drop of heat threshold with minimum effective doses of 0.3, 0.3, 10 and 30 mg/kg, and ED50 values of 0.5, 3, 18 and 100 mg/kg, respectively. Thermal hyperalgesia was also decreased by intraplantar treatment with morphine (10 μg), diclofenac (10 μg) or ibuprofen (100 μg). In conclusion, the mild heat injury-induced drop of the noxious heat threshold measured with the increasing-temperature water bath is a novel thermal hyperalgesia model highly sensitive to both opioid and non-opioid analgesics upon systemic or local administration.