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Schmerzinhibition durch Opioide – neue Konzepte

Pain inhibition by opioids—new concepts

Zusammenfassung

Hintergrund

Opioide sind die ältesten und stärksten Schmerzmedikamente, allerdings sind sie durch gefährliche Nebenwirkungen wie Atemdepression, Suchtpotenzial, Sedierung, Übelkeit und Obstipation limitiert. Die klinische Anwendung ist unbestritten in der Behandlung von akutem (z.B. perioperativem) und tumorassoziiertem Schmerz, jedoch hat die Langzeitanwendung bei chronischem Nichttumorschmerz zunehmend Kritik erfahren und zur aktuellen „Opioidkrise“ beigetragen.

Fragestellung und Ziele

Diese Übersicht behandelt pharmakologische Grundlagen und neue Forschungsstrategien zur Reduktion von Nebenwirkungen. Mechanismen der Schmerzentstehung und -inhibition sowie anderer Opioidwirkungen werden beschrieben. Zur Illustration der klinischen Situation und medizinischer Probleme werden pathophysiologische Veränderungen des Opioidsystems wie Plastizität von Opioidrezeptoren, Signalwegen, endogener Opioide, zentraler und peripherer Wirkorte diskutiert.

Schlussfolgerungen

Der epidemische Fehlgebrauch und Missbrauch von Opioiden hat gezeigt, dass große Wissenslücken in der Behandlung von chronischem Schmerz bestehen, dass Interessenkonflikte und die Validität von Modellen in der Medikamentenentwicklung stärker berücksichtigt werden müssen, und dass dringend neue Schmerzmedikamente ohne Suchtpotenzial gebraucht werden. Aktuell erscheinen die Verstärkung endogener Opioidwirkungen und die selektive Aktivierung peripherer Opioidrezeptoren am vielversprechendsten.

Abstract

Background

Opioids are the oldest and most potent drugs for the treatment of severe pain but they are burdened by detrimental side effects, such as respiratory depression, addiction potential, sedation, nausea and constipation. Their clinical application is undisputed in the treatment of acute (e.g. perioperative) and cancer pain but their long-term use in chronic pain has met increasing criticism and has contributed to the current “opioid crisis”.

Objectives

This article reviews the pharmacological principles and new research strategies aiming at novel opioids with reduced side effects. The basic mechanisms underlying pain and opioid analgesia and other effects of opioids are outlined. To illustrate the clinical situation and medical problems, the plasticity of opioid receptors, intracellular signaling pathways, endogenous and exogenous opioid receptor ligands, central and peripheral sites of analgesic and side effects are discussed.

Conclusion

The epidemic of opioid misuse has shown that there is a lack of fundamental knowledge about the characteristics and management of chronic pain, that conflicts of interest and validity of models must be more intensively considered in the context of drug development and that novel analgesics with less addictive potential are urgently needed. Currently, the most promising perspectives appear to be augmenting endogenous opioid actions and the selective activation of peripheral opioid receptors.

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Förderung

Unterstützung durch Bundesministerium für Bildung und Forschung (0316177B/C1, 01EC1403E, 01EC1403F) und Europäische Kommission (EU FP7-HEALTH-2013-INNOVATION-1; No. 602891-2).

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Correspondence to C. Stein.

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C. Stein ist als Erfinder im US Patent 9133120 B2 und Europäischen Patent 2 801 046 gelistet.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

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Stein, C. Schmerzinhibition durch Opioide – neue Konzepte. Schmerz 33, 295–302 (2019). https://doi.org/10.1007/s00482-019-0386-y

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Schlüsselwörter

  • Analgesie
  • Entzündung
  • Verletzung
  • Opioidrezeptoren
  • Signalwege

Keywords

  • Analgesia
  • Inflammation
  • Injury
  • Opioid receptors
  • Signaling pathways