RATIONALE: Studies have demonstrated that both pain and opioids have actions on the central nervous system that may interfere with cognitive function, but their effects have mainly been analysed separately and not as an integrated process.

OBJECTIVE: The objective of this study is to test two hypotheses: (1) the analgesic effect of opioids improves cognitive function by decreasing pain, and (2) pain antagonizes cognitive effects of opioids.

METHODS: Randomized, placebo-controlled, crossover study. Three experiments were conducted with 22 healthy males. Sustained attention, memory and motor function/attention/mental flexibility were evaluated by continuous reaction time (CRT), verbal fluency test (VFT) and trail making test-B (TMT-B), respectively. In the 1st experiment, the cognitive effects of experimental tonic pain of mild and moderate intensities produced by a computer-controlled pneumatic tourniquet cuff were assessed; in the 2nd, the effects of saline solution and remifentanil were assessed in the absence of pain; and in the 3rd experiment, the cognitive effects of moderate pain intensity relieved by remifentanil infusion were assessed followed by increasing pain to moderate intensity during a constant remifentanil infusion.

RESULTS: The first two experiments demonstrated that pain and remifentanil impaired CRT. In the 3rd experiment, remifentanil infusion relieving pain significantly impaired CRT and further deterioration was noted following increasing pain intensity.

CONCLUSION: Pain and remifentanil seemed to have additive deleterious cognitive effects. This study represents an initial step to enhance our basic understanding of some of the cognitive effects following a painful stimulus and an opioid infusion separately and combined in a sequence comparable to clinical settings.