The increasing-temperature hot-plate test: An improved test of nociception in mice and rats

Abstract

The increasing-temperature hot-plate test has several advantages compared to the conventional hot-plate test, but available equipment has been impractical and restricted with regard to stimulus control. We now describe an apparatus consisting of an aluminum plate that is heated and cooled by Peltier elements in contact with its lower surface. Several plates can be used simultaneously, individually controlled by electronic proportional feedback circuits. The set temperature of the feedback circuit is controlled by a computer program run on an IBM XT-compatible PC, so that a linear increase in temperature is achieved. Experiments were performed using rats and mice, with hindpaw licking as an end-point criterion. Experiments with various heating rates showed that 3.0° C/min is the lowest rate that can be applied without signs of stress in the animals. On the basis of the recorded data, nociceptive temperature thresholds were calculated to be approximately 44.5°C for both rats and mice. Inspection of the paws after analgesic treatment and exposure to different end-point temperatures suggested that a cutoff temperature of 50°C should be employed to minimize tissue damage. Testing at ambient temperatures of 18° and 28°C yielded similar results for rats, whereas mice responded at significantly higher plate temperatures in the colder environment. Dose-related antinociceptive effects were demonstrated for morphine and paracetamol in both species. The results confirm that the increasingtemperature hot-plate test is a valuable test of nociception, which is also suitable for demonstrating the antinociceptive effects of nonopioid analgesics. The test may also be used to estimate the nociceptive temperature threshold.