Interleukin-17 sensitizes joint nociceptors to mechanical stimuli and contributes to arthritic pain through neuronal interleukin-17 receptors in rodents
| Autor: | Matthias Ebbinghaus, Rolf Bräuer, Christian König, Gisela Segond von Banchet, Hans-Georg Schaible, Susanne Hensellek, Frank Richter, Gabriel Natura |
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| Rok vydání: | 2012 |
| Předmět: |
MAPK/ERK pathway
Male Patch-Clamp Techniques Knee Joint Immunology Arthritis Pain Pharmacology Proinflammatory cytokine Injections Intra-Articular Mice Rheumatology Ganglia Spinal Immunology and Allergy Medicine Animals Pharmacology (medical) Patch clamp Antigens Rats Wistar Receptor Extracellular Signal-Regulated MAP Kinases Cells Cultured Neurons Receptors Interleukin-17 business.industry Interleukin-17 Antibodies Monoclonal Nociceptors medicine.disease Arthritis Experimental Rats Mice Inbred C57BL Disease Models Animal Nociception nervous system Hyperalgesia Anesthesia Nociceptor Signal transduction business Proto-Oncogene Proteins c-akt |
| Zdroj: | Arthritis and rheumatism. 64(12) |
| ISSN: | 1529-0131 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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