Maximum tolerated temperature in the rat tail: a broadly sensitive test of analgesic activity

The methods most frequently employed for the study of analgesic activity of opiates are those based on thermal stimuli (hot-plate, tail-flick, TWR). These tests, however, are only sensitive for opiates which are pure agonists. In this work, we propose a modification of the TWR method capable of detecting analgesic activity in both agonist and agonist-antagonist opiates. In addition, non-opiate analgesics also show activity in this test. The ED50 (mg/kg, i.p.) of the substances studied, administered 30 min before commencement of the test, were as follows: buprenorphine: 0.02; methadone: 0.08; morphine: 1.9; pentazocine: 4.5; d-propoxyphene: 5.5; codeine: 7.6; pethidine: 9.2; zomepirac: 20.1; suprofen: 138.0; acetylsalicylic acid: 453.4. There was a statistically significant linear correlation between the results obtained by the proposed method (MTT) and those of some of the most frequently used methods for the study of analgesic agents (writhing induced by phenylbenzoquinone, acetic acid, acetylcholine bromide, hot-plate test and rat tail withdrawal test). The simplicity of the method makes it suitable for use in the battery of screening tests for analgesic activity of both narcotic and non-narcotic substances.