The Role of Interleukin-1β in Arthritic Pain Main Involvement in Thermal, but Not Mechanical, Hyperalgesia in Rat Antigen-Induced Arthritis

被引:88
作者
Ebbinghaus, Matthias
Uhlig, Benjamin
Richter, Frank
von Banchet, Gisela Segond
Gajda, Mieczyslaw
Braeuer, Rolf
Schaible, Hans-Georg
机构
[1] Jena University Hospital, Friedrich Schiller University of Jena, Institute of Physiology I/Neurophysiology, D-07740 Jena
来源
ARTHRITIS AND RHEUMATISM | 2012年 / 64卷 / 12期
关键词
TUMOR-NECROSIS-FACTOR; COLLAGEN-INDUCED ARTHRITIS; DORSAL-ROOT GANGLION; RECEPTOR ANTAGONIST; JOINT PAIN; KNEE-JOINT; TNF-ALPHA; CUTANEOUS HYPERALGESIA; INFLAMMATION; SENSITIZATION;
D O I
10.1002/art.34675
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective. Interleukin-1 beta (IL-1 beta) is considered a pronociceptive cytokine, but its role in the generation of arthritic pain is unknown. The aim of this study was to investigate the role of IL-1 beta in arthritic pain and to explore the antinociceptive potential of the IL-1 receptor type I (IL-1RI) antagonist anakinra. Methods. Antigen-induced arthritis (AIA) was induced in rats. Expression of IL-1RI in the dorsal root ganglia (DRGs) was determined, and the effects of anakinra on inflammation, pain-related behavior, and receptor expression were assessed. In cultured DRG neurons, the effect of IL-1 beta on the expression of the transient receptor potential vanilloid 1 (TRPV-1) ion channel was examined. Recordings of action potentials from joint nociceptors were made after intraarticular injection of IL-1 beta into the rat knee joints. Results. AIA generated pronounced and persistent mechanical and thermal hyperalgesia, and IL-1RI expression in the lumbar DRGs was significantly up-regulated. Treatment with anakinra did not significantly reduce the severity of arthritis or mechanical hyperalgesia, but did result in a pronounced reduction in thermal hyperalgesia. In cultured DRG neurons, IL-1 beta up-regulated the expression of TRPV-1, a major transduction molecule involved in thermal hyperalgesia. During AIA, anakinra treatment down-regulated the expression of TRPV-1, consistent with the pronounced reduction in thermal hyperalgesia. IL-1 beta increased the mechanosensitivity of C-fibers of the joint, but reduced the mechanosensitivity of A delta-fibers, thus having opposite effects on these mechanonociceptive nerve fibers. Conclusion. In the context of arthritic knee pain, IL-1 beta and IL-1 receptors appear to be involved in thermal, rather than mechanical, hyperalgesia. Therefore, neutralization of IL-1 beta may be mainly antinociceptive in disease states characterized by thermal hyperalgesia, but not in disease states mainly characterized by mechanical hyperalgesia.
引用
收藏
页码:3897 / 3907
页数:11
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