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 its duration of a new sustained-release preparation of tramadol in an experimental pain model based on pain-related chemosomatosensory evoked potentials (CSSEPs) and subjective intensity estimates of painful phasic and tonic stimuli. 2. Twenty volunteers participated in a randomised, double-blind, three-fold cross-over study. Measurements were obtained before and 0.5, 1, 4, 6, and 12 h after administration of the drug (100 mg, 200 mg and placebo orally). CSSEPs were recorded after stimulation of one nostril with phasic, painful CO2 pulses. The other nostril was stimulated with a constant stream of dry air, which produced a tonic painful sensation. Subjects rated the perceived intensity of phasic and tonic stimuli via visual analogue scales. In order to test for nonspecific effects, acoustic evoked potentials (AEPs) were recorded, the 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 observation period of 12 h, demonstrating the prolonged duration of the analgesic effect. 4. A dose-related significant decrease could be observed for the estimates of tonic pain. Similar to the decrease of amplitudes of the CSSEP, the reduction of the ratings of tonic pain outlasted the observation period of 12 h. The observed slight decrease in the estimates of phasic pain under medication did not reach a statistically significant level when compared with placebo. No significant effect could be demonstrated for the perception of the phasic and the tonic pain as determined by the McGill-Questionnaire. 5. A significant dose-related increase in the estimates of the side effects 'drowsiness', 'vertigo' and 'sickness' but not for 'tiredness' could be demonstrated.

RCT Entities:   Population Interventions Outcomes