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.