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Opioidvermittelte Analgesie und Hyperalgesie

Dr. Jekyll und Mr. Hyde der Schmerztherapie

Opioid-induced analgesia and hyperalgesia

  • Schwerpunkt: Opioide
  • Published:
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Zusammenfassung

Opioide sind Mittel der ersten Wahl in der Therapie mittelschwerer bis starker akuter und chronischer Schmerzzustände. Allerdings können Opioide auch zu einer Schmerzverstärkung führen, welche auf einer Aktivierung pronozizeptiver Systeme beruht.

Neben einer akuten Rezeptordesensibilisierung und einer Hochregulation der Adenylylzyklaseaktivität sind insbesondere die Aktivierung des N-Methyl-D-Aspartat- (NMDA-)Rezeptorsystems und die deszendierende Fazilitierung den antinozizeptiven Eigenschaften des Opioids entgegengerichtet. So können schon nach kurzzeitiger Anwendung Sensibilisierungsprozesse induziert werden, die einen Teil der analgetischen Wirkung des Opioids maskieren und noch viele Tage nach dem Absetzen nachweisbar sein können.

Die Toleranzentwicklung muss als Ungleichgewicht pronozizeptiver und antinozizeptiver Systeme gedeutet werden. Nach länger dauernder Anwendung von μ-Agonisten wurden neben einem ansteigenden Bedarf an Schmerzmitteln paradoxe Schmerzzustände beobachtet. Durch eine Kombination der Opioide mit Substanzen anderer Klassen wie NMDA-Rezeptor-Antagonisten, α2-Agonisten oder nicht steroidalen antiinflammatorischen Analgetika (NSAID), durch Opioidrotationen oder Kombinationen von Opioiden mit unterschiedlicher Rezeptorselektivität können diese Sensibilisierungsprozesse unterdrückt und die Schmerztherapie optimiert werden.

Abstract

Opioids are frequently used for the treatment of moderate to severe acute and chronic pain. However, clinical evidence suggests that opioids can elicit increased sensitivity to noxious stimuli suggesting that administration of opioids can activate both, pain inhibitory and pain facilitatory systems.

Acute receptor desensitization via uncoupling of the receptor from G proteins, upregulation of the cAMP pathway, activation of the N-methyl-D-aspartate (NMDA) receptor system and descending facilitation have been proposed as potential mechanisms underlying opioid-induced hyperalgesia.

The tolerance results from a pain sensitization process more than from a decrease in the opioid effectiveness. Opioid-induced hyperalgesia and tolerance are observed both in animal and human experimental models. Brief exposures to μ-receptor agonists induce long-lasting hyperalgesic effects for days. Furthermore, the prolonged use of opioids in patients often requires increasing doses and may be accompanied by the development of abnormal pain. Successful strategies that may decrease or prevent opioid-induced hyperalgesia include the concomitant administration of drugs such as NMDA antagonists, α2-agonists, or nonsteroidal anti-inflammatory drugs (NSAID), opioid rotation, or combinations of opioids with different receptor selectivity.

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  1. Klinik für Anästhesiologie, Universitätsklinikum, Erlangen

    W. Koppert

  2. Klinik für Anästhesiologie, Universitätsklinikum, Krankenhausstraße 12, 91054, Erlangen

    W. Koppert

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Koppert, W. Opioidvermittelte Analgesie und Hyperalgesie. Schmerz 19, 386–394 (2005). https://doi.org/10.1007/s00482-005-0424-9

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