Hyperalgesia during sedation: effects of barbiturates and propofol in the rat

Subhypnotic doses of thiopentone are considered to possess antianalgesic or hyperalgesic properties. In this study, we have tested the hypothesis that the coincidence of sedation and hyperalgesia is a property of both barbiturate and non-barbiturate anaesthetic agents. In a randomized, prospective, blinded study, the effects of slow (20 min) iv infusions of thiopentone, pentobarbitone, methohexitone or propofol on nociceptive threshold were measured in rats by tail pressure analgesimetry and compared with saline-infused control animals. Nociceptive thresholds were correlated with measurements of plasma drug concentrations and behavioural assessments. Comparison of pre-infusion nociceptive threshold with the lowest threshold obtained during drug infusion revealed decreases in all four treatment groups. As a percentage of the pre-infusion values, the decreases were: thiopentone: 42.5% (P < 0.001), pentobarbitone: 27.8% (P = 0.014), methohexitone: 24.9% (P = 0.013), propofol: 21.6% (P = 0.006). There were no changes in nociceptive threshold in the control groups. The relationship between nociceptive threshold and plasma drug concentration was usually characterized by an initial decline followed by a rise in nociceptive threshold as the plasma concentration and degree of sedation increased. The results support the hypothesis that hyperalgesia is a property of different anaesthetic agents when administered at sub-hynotic concentrations.