Co–Analgetika – heute und morgen – Eine rezeptorbasierte Übersicht analgetischer Therapieoptionen

Zusammenfassung

Die Entstehung und Leitung des Schmerzes erfolgt über zahlreiche periphere und zentrale Rezeptoren und Ionenkanäle, zusätzlich unterliegt sie einer körpereigenen zentralen Modulation. Neben den herkömmlichen Analgetika wurden Medikamente untersucht, die an weiteren Angriffspunkten der Schmerzbahn ansetzen und dadurch die Wirkung klassischer Analgetika verstärken.

Im Weiteren werden periphere Ansatzpunkte der Co–Analgetika dargestellt, darunter der Wirkmechanismus von Cannabinoiden, Capsaicin, Bisphosphonaten, Steroiden und Somatostatin. Ebenfalls erwähnt werden die Hemmer peripherer und zentraler Ionenkanäle, die eine Dämpfung der Schmerzleitung ermöglichen: Lokalanästhetika, Carbamazepin und Tolperison über Blockade des Natriumkanals; Gabapentin und Pregabalin über Blockade des Kalziumkanals.

Zuletzt werden zentrale analgetische Mechanismen beschrieben wie die NMDA–Rezeptor–Blockade durch Ketamin und Magnesium, die Stimulation der α2–Rezeptoren durch Clonidin, Tizanidin und Antidepressiva, die Stimulation des GABA–Rezeptors durch Baclofen und weitere Angriffspunkte von Ondansetron und Neostigmin.

Abstract

The sensation of pain arises through stimulation of peripheral nociceptors and is transmitted centrally involving several receptors and ion channels. In addition many endogenous physiologic painmodulating mechanisms exist. Besides of classical analgesics, numerous other drugs showed analgesic properties based on diverse modes of actions along the pain pathway. These co–analgesics, administered in combination with classical drugs, are able to reduce painful states of different origin.

We describe the peripheral action sites of co–analgesics, such as cannabinoids, capsaicin, bisphosphonates, steroids and somatostatin. We also summarise the effect of peripherally and centrally acting ion–channel blockers, e.g. local anaesthetics, carbamazepine and tolperisone working on sodium channels and gabapentine and pregabaline working on calcium channels.

Finally, central analgesic mechanisms are discussed, for instance the inhibition of NMDA–receptors by ketamine or magnesium, the stimulation of α2–receptors by clonidine, tizanidine or antidepressants, the activation of GABA–receptors through baclofen and other analgesic mechanisms of i.e. ondansetrone and neostigmine.

Schlüsselwörter:

Co–Analgetika - Schmerzmechanismen - akuter Schmerz - chronischer Schmerz

Keywords:

Co–analgesics - nociceptor - pain mechanism - acute pain - chronic pain

Kernaussagen

• Periphere analgetische Mechanismen sind die Blockade der Reizleitung durch Cannabinoide, die Überstimulation und damit Degeneration der Nervenbahn durch Capsaicin, die Hemmung der Entstehung von Reizstoffen durch Steroide und Bisphosphonate sowie die Stimulation schmerzhemmender Rezeptoren durch Somatostatin.

• Die Blockade peripherer und zentraler Ionenkanäle ermöglicht eine Dämpfung der Schmerzleitung. Lokalanästhetika, Carbamazepin, Oxcarbamazepin, Lamotrigin und Tolperison wirken über eine Natriumkanalblockade; Gabapentin und Pregabalin wirken über eine Kalziumkanalblockade.

• Zu den zentralen analgetischen Mechanismen zählen:

  • die Blockade des Schmerzrezeptors NMDA durch Ketamin, Dextrometorphan und Magnesium

  • die Stimulation des schmerzhemmenden α2–Rezeptors durch Clonidin, Dexmedetomidin, Tizanidin und Antidepressiva

  • die Stimulation des schmerzhemmenden GABA–Rezeptors durch Baclofen

  • die Blockade der deszendierenden Schmerzverstärkung am Serotoninrezeptor durch Ondansetron

  • die Stimulation des schmerzhemmenden Acetylcholinrezeptors durch Abbauverminderung mittels Neostigmin.

• Durch das Eingreifen an mehreren Orten in die Schmerzbahn mittels herkömmlicher Analgetika in Kombination mit oben beschriebenen Co–Analgetika kann die Schmerztherapie verbessert werden. Die Pharmakotherapie macht jedoch nur einen Teil der Schmerzbehandlung aus. Die psychische Schmerzwahrnehmung und –verarbeitung stellt einen weiteren wichtigen Angriffspunkt in der Schmerzbehandlung dar.

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