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Aktuelle Rheumatologie 2020; 45(05): 402-412
DOI: 10.1055/a-1203-1192
Übersichtsarbeit

Physiologie der Schmerzentstehung in der Peripherie

Physiology of Pain Generation in the Periphery
Annett Eitner
1   Klinik für Unfall-, Hand-, Wiederherstellungschirurgie, Universitätsklinikum Jena, Jena
,
Frank Richter
2   Institut für Physiologie 1, Universitätsklinikum Jena, Jena
,
Hans-Georg Schaible
2   Institut für Physiologie 1, Universitätsklinikum Jena, Jena
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Zusammenfassung

Dieser Beitrag gibt einen Überblick über den Kenntnisstand zu den Mechanismen der Schmerzentstehung im Gelenk. Er fokussiert sich auf den Vorgang der Nozizeption in nozizeptiven Nervenfasern des Gelenks und stellt dar, wie Krankheitsprozesse im Gelenk auf Nozizeptoren wirken. Während Nozizeptoren im normalen Gelenk eine hohe Erregungsschwelle besitzen und nur durch hochintensive Reize aktiviert werden, kommt es bei Gelenkerkrankungen häufig zu einer Sensibilisierung dieser Nervenfasern, sodass sie bereits auf leichte Reize (Bewegungen, Palpation) ansprechen und nach zentraler Verarbeitung Schmerzempfindungen auslösen. Eine Sensibilisierung wird meistens durch Entzündungsmediatoren ausgelöst, für die die Nozizeptoren Rezeptoren besitzen. Werden Nervenfasern im Erkrankungsprozess geschädigt, können neuropathische Schmerzmechanismen hinzukommen. Chronische Gelenkerkrankungen sind durch entzündliche und destruktive Prozesse charakterisiert. Sowohl bei primären Arthritiden als auch bei Arthrosen sind entzündliche Prozesse für die Sensibilisierung der Nozizeptoren verantwortlich. Dafür werden neben den Prostaglandinen auch proinflammatorische Zytokine und der Nervenwachstumsfaktor (NGF) verantwortlich gemacht, für die viele Nozizeptoren Rezeptoren exprimieren. Demgemäß sind diese Moleküle auch Target innovativer Schmerztherapien, z. B. die Gabe von Antikörpern gegen NGF bei Arthrose. Besonders für die Neutralisation von TNF ist ein direkt schmerzlindernder Effekt nachgewiesen, der aus der Unterbrechung von nozizeptiven Vorgängen am Nozizeptor resultiert. Der direkte pronozizeptive Effekt der Zytokine und Bindungsstellen für Fc-Fragmente von Antikörpern an Nozizeptoren zeigen, dass Immunmechanismen auch für die Schmerzentstehung große Bedeutung haben. Auch destruktive Gelenkprozesse können Schmerzen verursachen. So kann bereits die Osteoklastenaktivität im präklinischen Stadium einer Arthritis Schmerzen verursachen, und nach Ausbruch der Arthritis tragen Destruktionsprozesse zu Schmerzen bei. Inwieweit die Hemmung der Osteoklastenaktivität Gelenkschmerzen lindert, wird derzeit erforscht. Auch weitere neue Ansätze, peripher wirksame Opioide, Cannabinoide und Ionenkanalblocker werden dargestellt. Schließlich geht der Beitrag auf generelle/systemische Faktoren ein, die Krankheitsprozesse im Gelenk und die Schmerzentstehung beeinflussen. Hier wird in erster Linie die Bedeutung des Diabetes mellitus angesprochen. Diese Stoffwechselerkrankung stellt einen Risikofaktor für die Entwicklung von Arthrosen dar, und sie trägt zur Schmerzintensivierung bei. Dabei können verstärkte Entzündungsprozesse und auch neuropathische Schmerzkomponenten beteiligt sein.

Abstract

This review addresses our current knowledge on the mechanisms of pain generation in the joint. It focuses on the process of nociception in nociceptive nerve fibres of the joint and describes how disease processes in the joint act on nociceptors. While nociceptors of the normal joint have a high threshold for excitation and are activated only by stimuli of high intensity, disease processes in the joint often sensitise these nerve fibres such that they respond to stimuli of low intensity (movements, palpation) and, after processing in the central nervous system, elicit pain sensation. Sensitisation is frequently elicited by inflammatory mediators for which nociceptors express receptors. If nerve fibres are damaged during the disease process, neuropathic pain mechanisms may be triggered as well. Chronic joint diseases are characterised by inflammatory and destructive processes. In primary arthritis as well as osteoarthritis, inflammatory processes are responsible for the sensitisation of nociceptors. This process has been attributed to prostaglandins as well as, more recently, to proinflammatory cytokines and the nerve growth factor (NGF). For all of these mediators, receptors are expressed in nociceptors. Accordingly, these molecules are targets of innovative therapies, e. g. the application of antibodies to NGF to treat osteoarthritis pain. In particular, the neutralisation of TNF has been shown to elicit a direct rapid pain-reducing effect resulting from the interruption of nociceptive processes at the nociceptor. The direct pro-nociceptive effect of cytokines and the expression of binding sites for Fc fragments of antibodies in nociceptors show that immune mechanisms are important for the generation of pain. Pain can also be elicited by destructive joint processes. The activity of osteoclasts may elicit pain at the preclinical stage of arthritis, and after the outbreak of manifest arthritis, destructive processes contribute to pain. The extent to which the inhibition of osteoclast activity might alleviate pain is currently being investigated. This review also presents other novel approaches, peripherally acting opioids, cannabinoids and ion channel blockers. Finally, it addresses the importance of general/systemic factors which influence disease processes in the joint and pain generation. In particular, the importance of diabetes mellitus is addressed. This metabolic disease is a risk factor for the development of osteoarthritis and it contributes to pain aggravation, possibly by the involvement of more intense inflammatory processes as well as neuropathic pain components.

Schlüsselwörter

Nozizeptor - Sensibilisierung - Gelenkschmerz - Entzündungsmediatoren - Neuropathischer Schmerz

Key words

neuropathic pain - sensitization - inflammatory mediators - nociceptor - joint pain


Publikationsverlauf

Artikel online veröffentlicht:
25. August 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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