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The role of interleukin-1ss in arthritic pain: Main involvement in thermal but not in mechanical hyperalgesia in rat antigen-induced arthritis.

Authors: Ebbinghaus, M  Uhlig, B  Richter, F  Von Banchet, GS  Gajda, M  Brauer, R  Schaible, HG 
Citation: Ebbinghaus M, etal., Arthritis Rheum. 2012 Aug 29. doi: 10.1002/art.34675.
Pubmed: (View Article at PubMed) PMID:22933159
DOI: Full-text: DOI:10.1002/art.34675

OBJECTIVE.: Interleukin-1ss (IL-1ss) is considered a pronociceptive cytokine but its role in the generation of arthritic pain is unknown. This study had the aim to investigate the role of IL-1ss in arthritic pain and to explore the antinociceptive potential of the IL-1 receptor (IL-1R1) antagonist anakinra. METHODS.: Antigen-induced arthritis (AIA) was induced in rats. We studied the expression of IL-1R1 in the dorsal root ganglia (DRG) and explored the effect of anakinra on inflammation, pain-related behavior and receptor expression. In cultured DRG neurons we explored the effect of IL-1ss on the expression of the TRPV1 ion channel. Recordings of action potentials were made from joint nociceptors after intraarticular IL-1ss injection. RESULTS.: AIA generated pronounced and persistent mechanical and thermal hyperalgesia, and IL-1R1 in the lumbar DRGs was significantly upregulated. Treatment with anakinra did not significantly reduce the severity of arthritis and mechanical hyperalgesia but caused a pronounced reduction of thermal hyperalgesia. In cultured DRG neurons IL-1ss upregulated the expression of TRPV1, a major transduction molecule involved in thermal hyperalgesia. During AIA, anakinra downregulated the expression of TRPV1 consistent with the pronounced reduction of thermal hyperalgesia. IL-1ss increased the mechanosensitivity of C-fibers of the joint but reduced the mechanosensitivity of Adelta-fibers thus having opposite effects on mechanonociceptive C- and Adelta-fibers. CONCLUSION.: Concerning pain, IL-1ss and IL-1 receptors are rather involved in thermal than in mechanical hyperalgesia. Therefore neutralization of IL-1ss may be mainly antinociceptive in disease states characterized by thermal hyperalgesia but not in disease states mainly characterized by mechanical hyperalgesia.


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RGD Object Information
RGD ID: 6909175
Created: 2012-11-14
Species: All species
Last Modified: 2012-11-14
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.