Interleukin-17 sensitizes joint nociceptors to mechanical stimuli and contributes to arthritic pain through neuronal interleukin-17 receptors in rodents.

Autor:	Richter, Frank, Natura, Gabriel, Ebbinghaus, Matthias, Von Banchet, Gisela Segond, Hensellek, Susanne, König, Christian, Bräuer, Rolf, Schaible, Hans-Georg
Předmět:	ACADEMIC medical centers ANIMAL experimentation ARTHRITIS CHI-squared test ELECTROPHYSIOLOGY INFLAMMATION INTERLEUKINS MICE PAIN POLYMERASE chain reaction RESEARCH funding STATISTICS T-test (Statistics) WESTERN immunoblotting DATA analysis EQUIPMENT & supplies DISEASE complications
Zdroj:	Arthritis & Rheumatism; Dec2012, Vol. 64 Issue 12, p4125-4134, 10p
Abstrakt:	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. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
Externí odkaz:	Zobrazit plný text záznamu Plný text