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Opioid-induzierte Hyperalgesie

Pathophysiologie und Klinik

Opioid-induced hyperalgesia

Pathophysiology and clinical relevance

  • Schmerztherapie
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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, die auf einer Aktivierung pronozizeptiver Systeme beruht. Es konnte gezeigt werden, dass neben einer akute Rezeptordesensibilisierung und einer Hochregulation der Adenylylzyklaseaktivität insbesondere die Aktivierung des N-Methyl-D-Aspartat- (NMDA-)Rezeptor-Systems und die deszendierende Fazilitierung den antinozizeptiven Eigenschaften des Opioids entgegengerichtet sind. 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. Klinische Relevanz erhalten diese Befunde aus Studien, in denen nach der intraoperativen Anwendung hoher Dosen von μ-Agonisten vermehrte Schmerzen und ein erhöhter postoperativer Schmerzmittelverbrauch beobachtet wurde. Weiterhin werden nach länger dauernder Anwendung von μ-Agonisten oftmals 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 nichtsteroidalen antiinflammatorischen Analgetika (NSAIDs), durch Opioidrotationen oder Kombinationen von Opioiden mit unterschiedlicher Rezeptorselektivität können diese Sensibilisierungsprozesse unterdrückt und die Schmerztherapie optimiert werden.

Abstract

Opioids are the drugs of choice 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, up-regulation of the cAMP pathway, activation of the N-methyl-D-aspartate (NMDA) receptor system, as well as descending facilitation, have been proposed as potential mechanisms underlying opioid-induced hyperalgesia. Numerous reports exist demonstrating that opioid-induced hyperalgesia is observed both in animal and human experimental models. Brief exposures to μ-receptor agonists induce long-lasting hyperalgesic effects for days, which might by reflected by clinical observations that large doses of intraoperative μ-receptor agonists increased postoperative pain and morphine consumption. 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 like NMDA-antagonists, α2-agonists, or non-steroidal anti-inflammatory drugs (NSAIDs), opioid rotation or combinations of opioids with different receptor selectivity.

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Koppert, W. Opioid-induzierte Hyperalgesie. Anaesthesist 53, 455–466 (2004). https://doi.org/10.1007/s00101-004-0669-1

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