The development of acute opioid tolerance in humans remains controversial. We tested the hypothesis that continuous remifentanil infusion leads to rapid development of opioid tolerance. Twenty healthy male volunteers were enrolled onto a randomized, placebo-controlled, double-blinded, cross-over design study to receive a 3 h continuous infusion of remifentanil (0.08 microg x kg(-1) x min(-1)) or saline. Test procedures included determination of pain perception thresholds and pain tolerance thresholds to heat and cold and neuroselective sine wave constant current at 5 Hz and 250 Hz. Test procedures were performed at baseline and then repeated at 25, 55, 85, 115, and 160 min (heat/cold) and at 35, 65, 95, 125, and 170 min (electrical current) during infusion. No significant decrease of the pain threshold devolutions between 55 and 180 min after the start of infusion of remifentanil could be detected. In conclusion, no development of acute opioid tolerance was observed during constant remifentanil infusion of 3 h in volunteers.
Implications: The opioid remifentanil was applied to 20 volunteers at a constant concentration for 3 h while pain thresholds to temperature and current were repeatedly assessed. Our aim was to study whether thresholds decrease over time because of the rapid development of opioid tolerance. No development of rapid opioid tolerance was observed.