Fig. 3. Influence of 0.4 mg/kg morphine-6β-glucuronide (M6G) on experimental heat pain responses in human volunteers during background exposure to naloxone. During a naloxone background infusion, M6G causes an immediate and persistent hyperalgesic response. Naloxone was given as an intravenous bolus of 0.043 mg/kg ( down arrow ), 30 min before M6G injection ( up arrow ), followed by a continuous infusion of 0.043 mg/kg per hour. Values are mean ± SEM; symbols indicate different groups of 10 subjects. Significant main effects: M6G-naloxone, P < 0.001. Post hoc comparisons: *P < 0.05 versus t = 0. NRS = numerical rating pain scale. Reprinted with permission from van Dorp ELA, et al. Anesthesiology 2009; 110:1356–63.