Opioide und periphere Entzündungsmechanismen

Zusammenfassung

Lange galten Opioide als ausschließlich zentral wirksame Analgetika. Ende der 1980-iger Jahre gelang es erstmals, Opioidrezeptoren auf sensorischen Nervenfasern in peripheren Geweben nachzuweisen. Inzwischen kennen wir detailliert untersuchte Mechanismen eines peripheren Opioidsystems, das den Einfluss pathologischer Gewebeveränderungen auf Schmerzen, die lokale Wirkung von Opioiden an peripheren Nervenenden, die Produktion und Freisetzung von endogenen Opioidpeptiden aus Entzündungszellen sowie peripher vermittelte analgetische und anti-inflammatorische Effekte von Opioiden beinhaltet. Infolge dieser Fortschritte in der Grundlagenforschung kommen Erkenntnisse zum Wirkmechanismus von Opioiden in peripherem Gewebe mittlerweile in der Klinik zur Anwendung und haben sich in der Formulierung von Leitlinien niedergeschlagen. So wird z. B. zur postoperativen Analgesie nach Kniegelenksoperationen die intraartikuläre Injektion von Morphin als Therapiestandard empfohlen (http://www.guidelines.gov). Periphere opioidvermittelte Mechanismen zeichnen sich als vielversprechende Therapieansätze ab, insbesondere bei bereits länger bestehenden Entzündungserkrankungen. Zentrale Nebenwirkungen von Opioiden können bei ausschließlich peripherer Opioidwirkung ebenso umgangen werden wie die gefürchteten Nebenwirkungen einer chronischen Therapie mit nicht-steroidalen Antiphlogistika (NSAIDs).

Abstract

For ages opioids were believed to act solely as central analgesic drugs. In the late 1980s studies began to show that opioids not only activate opioid receptors in the brain and spinal cord but also those on peripheral sensory neurons. Since then, a detailed model of opioid pathways outside the central nervous system has been developed. It provides insight into the effects of pathological tissue changes on the generation of pain, the local action of opioids on peripheral neurons, the production and release of endogenous opioid peptides in immune cells, as well as endogenous peripherally mediated analgesic and anti-inflammatory effects of opioids. Subsequent to this progress in basic research, peripheral opioid effects have made their way from the bench to the bedside. For example, current clinical guidelines recommend the intra-articular injection of morphine after knee joint surgery for effective postoperative pain control (http://www.guidelines.gov). Peripheral mechanisms of opioid analgesia provide a tempting approach to pain treatment avoiding the adverse effects of centrally acting opioids and offering anti-inflammatory action without the dreaded side effects of non-steroidal anti-inflammatory drugs (NSAIDs).

Schlüsselwörter

periphere Analgesie - Opioidrezeptoren - Opioide - Entzündung

Key words

peripheral analgesia - opioid receptors - opioids - inflammation

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