DOSE-DEPENDENT TIME-COURSE OF THE ANALGESIC EFFECT OF A SUSTAINED-RELEASE PREPARATION OF TRAMADOL ON EXPERIMENTAL PHASIC AND TONIC PAIN

1 The aim of this study was to investigate the analgesic effect and it s duration of a new sustained-release preparation of tramadol in an ex perimental pain model based on pain-related chemosomatosensory evoked potentials (CSSEPs) and subjective intensity estimates of painful phas ic and tonic stimuli. 2 Twenty volunteers participated in a randomised , double-blind, three-fold crossover study. Measurements were obtained before and 0.5, 1, 4, 6, and 12 h after administration of the drug (1 00 mg, 200 mg and placebo orally). CSSEPs were recorded after stimulat ion of one nostril with phasic, painful CO2 pulses. The other nostril was stimulated with a constant stream of dry air, which produced a ton ic painful sensation. Subjects rated the perceived intensity of phasic and tonic stimuli via visual analogue scales. In order to test for no nspecific effects, acoustic evoked potentials (AEPs) were recorded, th e spontaneous EEG was analysed in the frequency domain, the subject's vigilance was assessed in a tracking task, and the side effects of the drug were monitored. 3 The sustained-release preparation of tramadol produced a significant dose-related decrease in CSSEP amplitudes when compared with placebo. The reduction in amplitudes outlasted the obser vation period of 12 h, demonstrating the prolonged duration of the ana lgesic effect. 4 A dose-related significant decrease could be observed for the estimates of tonic pain. Similar to the decrease of amplitude s of the CSSEP, the reduction of the ratings of tonic pain outlasted t he observation period of 12 h. The observed slight decrease in the est imates of phasic pain under medication did not reach a statistically s ignificant level when compared with placebo, No significant effect cou ld be demonstrated for the perception of the phasic and the tonic pain as determined by the McGill-Questionnaire. 5 A significant dose-relat ed increase in the estimates of the side effects 'drowsiness', 'vertig o' and 'sickness' but not for 'tiredness' could be demonstrated.