Fig. 4. Influence of 0.4 mg/kg morphine-6β-glucuronide (M6G) and placebo on experimental heat pain responses in human volunteers during background exposure to saline and background exposure to naloxone. During a saline (  A ) and naloxone (  B ) background infusion, M6G causes an immediate and persistent hyperalgesic response. In contrast, placebo produces no consistency in response independent of the background infusion (  C, saline, and  D, naloxone). Naloxone and saline were given as an intravenous bolus of 0.043 mg/kg (  down arrows ), 30 min before M6G or placebo injection (  up arrows ), followed by a continuous infusion of 0.043 mg/kg per hour. Values are mean ± SEM; different  symbols indicate different groups of 10 subjects. Significant main effects: (  A ) M6G–saline,  P < 0.01; (  B ) M6G–naloxone,  P < 0.001.  Post hoc comparisons: *  P < 0.05  versus t = 0. NRS = numerical rating pain scale.