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

Canadian Journal of Anaesthesia volume 42, pages 532–540 (1995)Cite this article

Abstract

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.

Résumé

On considère que les doses sous- hypotiques de thiopentone possèdent des propriétés antianalgésiques ou hyperalgésiques. Cette étude vérifie l’hypothèse selon laquelle la coïncidence de la sédation avec l’hyperalgie constitue à la fois une propriété des agents anesthésiques barbituriques et des non barbituriques. Au cours d’une élude randomisée, prospective et à l’aveugle, les répercussions sur le seuil nociceptif d’une perfusion lente (20 min) de thiopentone, pentobarbitone, méthohexitone et de propofol sont mesurées par analgésiométrie de compression sur la queue du rat et comparées avec des animaux de contrôle sous perfusion au soluté physiologique. Les seuils nociceptifs sont correlés avec les mesures de concentration plasmatique des drogues et par l’évaluation du comportement. La comparaison du seuil nociceptif avant la perfusion avec le seuil le plus bas obtenu pendant la perfusion révèle des diminutions dans tous les groupes de traitement. En pourcentage des valeurs de préinfusion, les diminutions sont les suivantes: thiopentone: 42,5% (P < 0.001), pentobarbitone: 27,8% (P = 0,014), méthohexitone: 24.9% (P = 0,013), propofol: 21,6% (P = 0,006). Il n’y a pas de changement dans les groupes contrôle au regard du seuil nociceptif. La relation entre le seuil nociceptif et la concentration plasmatique des drogues est ordinairement caractérisée par une baisse initiale suivie par une augmentation du seuil nociceptif à mesure que la concentration plasmatique et le niveau de sédation augmentent. Ces résultats supportent l’hypothèse selon laquelle l’hyperalgie serait une propriété de plusieurs anesthésiques quand ils sont administrés à des concentrations sous- hypnotiques.

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Affiliations

  1. Department of Anaesthesia, University of Calgary, Canada

    Alastair Ewen, David P. Archer, Naaznin Samanani & Sheldon H. Roth

  2. Department of Pharmacology and Therapeutics, University of Calgary, Canada

    Sheldon H. Roth

Authors
  1. Alastair Ewen
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  2. David P. Archer
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  3. Naaznin Samanani
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  4. Sheldon H. Roth
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Ewen, A., Archer, D.P., Samanani, N. et al. Hyperalgesia during sedation: effects of barbiturates and propofol in the rat. Can J Anaesth 42, 532–540 (1995). https://doi.org/10.1007/BF03011694

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Key words

  • anaesthetics, intravenous: methohexitone, pentobarbitone, propofol, thiopentone
  • measurement: nociceptive threshold, sedation
  • pain: hyperalgesia, nociception