Objective: The present study tested analgesia produced by a new controlled release formulation of tramadol. The investigation employed an experimental pain model based on chemo-somatosensory event-related potentials (CSSERP) in response to painful chemical stimuli applied to the nasal mucosa.Study: Twenty healthy volunteers participated in the experiments, which followed a controlled, randomised, double-blind, 3-way cross-over design. Each of the three medications (tramadol 100 mg [T100], tramadol controlled release 100 mg [TCR100] and tramadol controlled release 150 mg [TCR150]) was administered orally to fasting subjects. There was at least a 6 day washout period between tests. Each experiment was divided into five sessions, which took place before and 2, 4, 6, and 12 h after drug administration. In addition to the assessment of CSSERP, subjects rated the intensity of both the tonic and phasic painful stimuli. Nonspecific drug effects were also monitored by means of frequency analysis of the spontaneous EEG, ratings of adverse effects, and the subjects' performance in a tracking task.Results: The significant reduction of amplitude N1 at central recording positions indicated that TCR150 was the most effective analgesic 12 h after administration. Both 6 and 12 h after administration TCR100 was more effective in terms of analgesia compared to T100. In addition, TCR100 appeared to produce fewer adverse effects than the standard formulation of tramadol.Conclusions: The controlled release formulation can be expected to become a valuable tool in peroral therapeutic regimens for chronic pain.