Document Detail

Interleukin-17 sensitizes joint nociceptors to mechanical stimuli and contributes to arthritic pain through neuronal interleukin-17 receptors in rodents.
MedLine Citation:
PMID:  23192794     Owner:  NLM     Status:  In-Data-Review    
OBJECTIVE: Interleukin-17 (IL-17) is considered a proinflammatory cytokine, but whether neuronal IL-17 receptors contribute to the generation of arthritic pain is unknown. This study was undertaken to explore whether IL-17A acts on neurons, whether it sensitizes joint nociceptors, and whether neutralization of IL-17 is antinociceptive.
METHODS: We recorded action potentials from rat joint nociceptors after intraarticular injection of IL-17A. We studied the expression of the IL-17A receptor in the rat dorsal root ganglia (DRG), explored the effect of IL-17A on signaling pathways in cultured rat DRG neurons, and using patch clamp recordings, monitored changes of excitability by IL-17A. We tested whether an antibody to IL-17 influences pain behaviors in mice with antigen-induced arthritis (AIA).
RESULTS: A single injection of IL-17A into the rat knee joint elicited a slowly developing and long-lasting sensitization of nociceptive C fibers of the joint to mechanical stimuli, which was not attenuated by neutralizing tumor necrosis factor α or IL-6. The IL-17A receptor was visualized in most rat DRG neurons, the cell bodies of primary sensory neurons. In isolated and cultured rat DRG neurons, IL-17A caused rapid phosphorylation of protein kinase B and ERK, and it rapidly enhanced excitability. In mice with unilateral AIA in the knee, an antibody against IL-17 improved the guarding score and reduced secondary mechanical hyperalgesia at the ipsilateral paw.
CONCLUSION: Our findings indicate that IL-17A has the potential to act as a pain mediator by targeting IL-17 receptors in nociceptive neurons, and these receptors are particularly involved in inflammation-evoked mechanical hyperalgesia.
Frank Richter; Gabriel Natura; Matthias Ebbinghaus; Gisela Segond von Banchet; Susanne Hensellek; Christian König; Rolf Bräuer; Hans-Georg Schaible
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  64     ISSN:  1529-0131     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4125-34     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2012 by the American College of Rheumatology.
Institute of Physiology I/Neurophysiology, Jena University Hospital-Friedrich Schiller University Jena, Jena, Germany.
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