Aspects on tail-flick, hot-plate and electrical stimulation tests for morphine antinociception.
The objective of this study was to compare the results of three nociceptive tests, tail-flick, hot-plate and electrical stimulation vocalisation, reflecting the responses from different sites in the CNS. A subcutaneous morphine dose (5 mg/kg) was administered to three parallel groups of rats in which the nociceptive response was measured by one of the three methods. The baseline decreased during the period of measurement for the hot-plate test, but remained stable for the other methods. The spinally mediated tail-flick response was more sensitive to the morphine effects as compared to the supraspinally mediated hot-plate and electrical stimulation vocalisation responses. The electrical stimulation vocalisation-test demonstrated more even effect-time profiles and less variability among the rats than did the tail-flick and the hot-plate methods. In the tail-flick group, 59% of the observations attained the cut-off latency at this morphine dose, leading to underestimation of the peak effect, the area under the effect curve (AUEC), and the variability among the rats. In the hot-plate group, 13% of the observations were at the cut-off latency, and 2% in the electrical stimulation vocalisation group. Different ways of presenting the data are discussed. In conclusion, the test selected for measuring the nociceptive response will influence the effect-time profile and subsequently any pharmacodynamic parameters describing it.
Gårdmark
M
M
Division of Biopharmaceutics and Pharmacokinetics, Uppsala, Sweden.
Höglund
A U
AU
Hammarlund-Udenaes
M
M
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D019540:Area Under Curve; D002490:Central Nervous System / Q000187:drug effects*; D004558:Electric Stimulation; D006358:Hot Temperature / Q000009:adverse effects; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D010147:Pain Measurement / Q000592:standards*; D011237:Predictive Value of Tests; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D000701:Analgesics, Opioid; D009020:Morphine